Perspectives in Pharmacy Practice: Trends in Pharmaceutical Care 9811692122, 9789811692123

Citation preview

Anantha Naik Nagappa Jovita Kanoujia Shvetank Bhatt Vaishnavi Naik   Editors

Perspectives in Pharmacy Practice Trends in Pharmaceutical Care

Perspectives in Pharmacy Practice

Anantha Naik Nagappa • Jovita Kanoujia • Shvetank Bhatt • Vaishnavi Naik Editors

Perspectives in Pharmacy Practice Trends in Pharmaceutical Care

Editors Anantha Naik Nagappa Amity Institute of Pharmacy Amity University Gwalior, Madhya Pradesh, India

Jovita Kanoujia Amity Institute of Pharmacy Amity University Gwalior, Madhya Pradesh, India

Shvetank Bhatt Amity Institute of Pharmacy Amity University Gwalior, Madhya Pradesh, India

Vaishnavi Naik Department of Pharmacy Practice Dayananda Sagar University Bengaluru, Karnataka, India

ISBN 978-981-16-9212-3 ISBN 978-981-16-9213-0 https://doi.org/10.1007/978-981-16-9213-0

(eBook)

# The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Preface

The importance of pharmacists is very well recognized by the service they render to patients in developed countries. Pharmacists are specialized in helping patients in improving the quality of life by carefully checking the suitability of prescribed medications, outcomes of therapy, and lifestyle of patients, which improves health status and minimizes sufferings. The services provided by pharmacists are collectively called as pharmacy practice, especially as pharmaceutical care. Pharmaceutical care delivery is becoming all important as all healthcare professionals and related stakeholders are becoming aware of the risks associated with medicines. The significance of careful consideration of medicine usage and the advantages it offers had opened the eyes of all healthcare professionals and patients who are interested in using medicines for better quality of life and avoiding unnecessary suffering due to irrational use of medicines. Pharmacy practice and pharmaceutical care are gaining popularity due to the core values they offer, like practice of pharmacoeconomics, rational outcomes, and evidence-based practice for an individual patient. This practice, being unorganized and seldom documented, has gone unnoticed. The main cause for this is the pharmacist himself/herself. The activities and services carried out by a pharmacist go unnoticed as pharmacists themselves do not like to be mentioned or to be in limelight. The issues of medication errors, irrational use of medicines, and ignorance about generics are collectively fought by pharmacy practice. It is the field which is going to change the practice of medicine from product-centered prescription to patient-centric care. In this book, we have attempted to peep into the future and get the perspective of pharmacy practice in future. This book is intended to serve as a latest and ample resource for the students, academicians, and scientists working in the field of pharmacy practice. We dedicate this book for the patients in the world and the pharmacists who naturally assume the responsibility of patients and their health. We wish to thank Amity University, Madhya Pradesh, and Dayananda Sagar University, Bangalore,

v

vi

Preface

for their support in writing this book. Nevertheless, we wish to acknowledge the help and encouragement received from Dr. GBKS Prasad from Jiwaji University, Gwalior, Madhya Pradesh, rendered Mr. Negi, in completing this book. Gwalior, India Gwalior, India Gwalior, India Bengaluru, India

Anantha Naik Nagappa Shvetank Bhatt Jovita Kanoujia Vaishnavi Naik

Acknowledgments

We are highly indebted to the profound help given by Dr. GBKS Prasad, Professor, Department of Biochemistry, Jiwaji University, Gwalior. We are thankful to our Honorable Vice Chancellor Lt. Gen. V. K. Sharma, AVSM (Retd.), Amity University, Madhya Pradesh, Gwalior, India, for his continuous encouragement. We are grateful to Mr. Rajiv Dwivedi, Faculty, Amity Business School, Amity University, Madhya Pradesh, Gwalior, for his support during the writing of this book. We would also like to acknowledge the support of Mr. Makan Singh Negi for the typing and formatting of the content. Finally, I would like to express my wholehearted appreciation to the faculty, students, and staff members of Amity Institute of Pharmacy, Amity University, Madhya Pradesh, Gwalior.

vii

Contents

1

2

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and Hospital Pharmacy . . . . . . . . . . . . . . . . . . A. N. Nagappa and Vaishnavi Naik

1

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A. N. Nagappa and Vaishnavi Naik

13

3

Pharmacist: Background, Knowledge, and Skills . . . . . . . . . . . . . . A. N. Nagappa and Vaishnavi Naik

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on Outcomes, Quality of Life, and Cost of Treatments . . . . A. N. Nagappa and Vaishnavi Naik

5

6

7

8

Communication: Inter- and Intracommunication, Provider-Patient Communication, Perspectives and Approaches, Provider Competencies and Communication Skill, Patient Competencies and Communication Skills, Equity in Healthcare Delivery, Patient Counseling, Medication History, and Patient Education . . . . . . . . . A. N. Nagappa and Vaishnavi Naik Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A. N. Nagappa and Vaishnavi Naik Clinical Pharmacy Services: Drug and Poison Information, Ward Round Participation, Drug-Drug Interaction and Drug-Food Interaction, Prescription Analysis, PTC Activities, Formulary Management, and TDM Services . . . . . . . . . . . . . . . . . . . . . . . . . . . A. N. Nagappa and Jovita Kanoujia

27

39

59

73

87

Community Pharmacy Services: Dispensing of Prescription, Home Medication Review, Treatments of Minor Ailments, Screening and Monitoring of Chronic Disease, and Maintaining of Patient Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 A. N. Nagappa and Jovita Kanoujia ix

x

Contents

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription, Extempore Preparation, Nuclear Medicine, Narcotic Drug Storage and Dispensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 A. N. Nagappa and Jovita Kanoujia

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940, Pharmacy Act 1948, Pharm D Regulations, Bridge Course for Pharmacist, Pharm Drugs and Magic Remedies Act, Pharmacy Practice Regulations 2015, and Jan Aushadhi Scheme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 A. N. Nagappa and Jovita Kanoujia

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance, Pediatrics, Geriatrics, Women During Pregnancy, Cancer, Pain Management, and Nutrition . . . . . . . . . . . 181 A. N. Nagappa and Jovita Kanoujia

12

Medication Therapy Management: Importance and Practice . . . . . 217 A. N. Nagappa and Jovita Kanoujia

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 A. N. Nagappa and Jovita Kanoujia

14

Clinical Pharmacokinetics: ADME, Bioavailability and Bioequivalence, and Dosage Adjustments in CKD and Liver Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 A. N. Nagappa and Shvetank Bhatt

15

Biotherapeutics: Monoclonal Antibodies, Biologicals, Biogenerics, Biosimilar, and Biobetters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 A. N. Nagappa and Shvetank Bhatt

16

Introduction to Clinical Trials and Biostatistics . . . . . . . . . . . . . . . . 263 A. N. Nagappa and Shvetank Bhatt

17

Introduction to Personalized Medicine and Pharmacogenomics . . . 279 A. N. Nagappa and Shvetank Bhatt

18

Introduction to Pharmacoeconomics and Outcome Research . . . . . 287 A. N. Nagappa and Shvetank Bhatt

19

Clinical Trials, Pharmacovigilance, and Drug Safety . . . . . . . . . . . . 307 A. N. Nagappa and Shvetank Bhatt

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical Trials (RCT) . . . . . . . . . . . . . . . . . . . . . . . . . 321 A. N. Nagappa and Shvetank Bhatt

About the Editors

Anantha Naik Nagappa is currently working in the capacity of Director at Amity Institute of Pharmacy, Amity University, Madhya Pradesh, Gwalior, India. He is backed by over 39 years of experience in pharmacy and has held various prestigious positions in the area of pharmacy. He specializes in the areas of clinical pharmacy, pharmacology, pharmacy practice, and social pharmacy. Dr. Nagappa has written three books and contributed over 50 book chapters, and he has more than 150 peerreviewed publications in reputed journals to his credit. He has completed five research projects funded by the government and pharmaceutical industry and is the recipient of many prestigious awards. He serves on the editorial board of various national and international journals and is a reviewer for various international journals as well. Jovita Kanoujia is currently serving as an Assistant Professor of Pharmaceutics at Amity Institute of Pharmacy, Amity University, Madhya Pradesh, Gwalior, India. Dr. Kanoujia received her Ph.D. with the specialization in Pharmaceutical Sciences from Babasaheb Bhimrao Ambedkar University (A Central University), Lucknow, India, with high research output in the area of novel drug delivery system. She has published several research papers in national and international high-impact peerreviewed journals and three book chapters with internationally renowned publishers. Shvetank Bhatt has done M. Pharm. in Pharmacology from Manipal College of Pharmaceutical Sciences, MAHE, Manipal, Karnataka, in 2006 and Ph.D. in Neuropharmacology from Birla Institute of Technology & Science (BITS) Pilani, Pilani Campus, Rajasthan. He is currently working as a Professor in Amity Institute of Pharmacy, Amity University, Madhya Pradesh (AUMP), Gwalior. He has total 15 years of industrial and academic research experience. He is a recipient of Prof. Duggirala Visweswaram and Prof. Sreemantalu Satyanarayana Award. He has published more than 65 papers in various journals of national and international repute.

xi

xii

About the Editors

Vaishnavi Naik has done Pharm. D. from Manipal University, Manipal, Karnataka. She has worked as Assistant Professor in the Department of Pharmacy Practice of Dayanand Sagar University, Bangalore. She has work experience as a drug safety associate in Bioclinica, Mysore. She is a recipient of ACPE travel grant and ISPOR Dublin travel grant. She has done FIP Pharmabridge program in community pharmacy. She has published several research articles, reviews, case studies, and book chapters.

Abbreviations

AACP ACMS ACPI ADME ADR AED AIIMS AIOCD ALF APTI AQLQ ARR ASHP BMI BNF BP BP BPPI BPS BRAF CABG CAM CAR-T CAT cDNA CHD Cl CMA CMS CNS COOP COPD CRF

American Association of Colleges of Pharmacy Anticoagulation Case Management Service Association of Community Pharmacists of India Absorption, distribution, metabolism, and excretion Adverse drug reaction Antiepileptic drug All India Institute of Medical Sciences All India Organization of Chemists and Druggists Acute liver failure Association of Pharmacy Teachers of India Asthma Quality of Life Questionnaire Absolute risk reduction American Society of Health System for Pharmacists Body mass index British National Formulary Blood pressure British Pharmacopoeia Bureau of Pharma Public Sector Undertakings of India Board of Pharmacies Specialties A human gene that encodes a protein called B-Raf Coronary artery bypass graft Complementary and alternative medicine Chimeric antigen receptor T cell Critically appraised topic Complementary deoxyribonucleic acid Coronary heart diseases Clearance Cost minimization analysis Centre for Medicare Central nervous system Cooperative Information Project Chronic obstructive pulmonary disease Case record form xiii

xiv

CVD CYP D&C Rules D&M Act DALY’s DIC DLQI DMARDS DOTS DPCO DQOL DRPs DTAB EBM ECG ECHO EDL EOQ EORTC EQ-5D FARM FIP GDP GERD GFR GOI HCPS HCV HDL-C HEOR HITI HIV HMO HMR HPP HRQOL HUI IADVL IB ICER ICH-GCP ICU

Abbreviations

Cardiovascular disease Cytochrome P Drugs and Cosmetics Rules Drugs and Magic Remedies Act Disability-adjusted life years Drug Information Centre Dermatology Life Quality Index Disease-modifying antirheumatic drugs Direct observed therapy Drug price control order Diabetes quality of life measure Drug-related problems Drug Technical Advisory Board Evidence-based medicine Electrocardiogram Economic, clinical, and humanistic outcome model Essential drugs list Economic order quantity European Organization for Research and Treatment of Cancer EuroQol Instrument Findings, Objective Findings, Assessment, and Plan Federation of Pharmacy International Gross domestic product Gastroesophageal reflux disease Glomerular filtration rate Government of India Healthcare providers Hepatitis C High-density lipoprotein-cholesterol Health economics and outcome research Health Information Technology Institute Human immunodeficiency virus Health maintenance organizations Home medication review Human papillomavirus Health-related quality of life Health Utilities Index The Indian Association of Dermatologists, Venereologists and Leprologists Investigator’s Brochure Incremental cost-effectiveness ratio The International Council for Harmonisation of Technical Requirements for Pharmaceuticals-Good Clinical Practice Intensive care unit

Abbreviations

IDMA IEC IHPA INC INCB INR IP IPGA IPR IRB IV KDQOL-SF LBF LDL-C MAP MCI ME MEDLARS MRI MRTP MTC MTM NAC NAPQI NCD NDPS Act NFI NGOs NHP NPPA NPS NSAIDS OCEBM OPSS OPPI OR ORS OS OTC P&HC PC PCC PCI PCR PE

xv

Indian Drug Manufacturers’ Association Independent Ethics Committee Indian Hospital Pharmacists of India Indian Nursing Council International Narcotics Control Board International normalized ratio Indian Pharmacopoeia Indian Pharmacy Graduates’ Association professionals Intellectual Property Rights Institutional Review Board Intravenous Kidney Disease Quality of Life Short Form Liver blood flow Low-density lipoprotein-cholesterol Medication Action Plan Medical Council of India Medication errors Medical Literature Analysis and Retrieval System Magnetic resonance imaging Monopolies and Restrictive Trade Practices Act Minimum toxic concentration Medication therapy management N-acetylcysteine N-acetyl-p-benzoquinone imine Noncommunicable diseases Narcotic Drugs and Psychotropic Substances Act National Formulary of India Nongovernmental organization Nottingham Health Profile National Pharmaceutical Pricing Authority Nuclear pharmacy services Nonsteroidal anti-inflammatory drug Oxford Centre for Evidence-Based Medicine Oncology Pharmacy Specialists Organization of Pharmaceutical Producers of India Odds ratio Oral rehydration solution Oculus sinister (left eye) Over the counter Patient and health consumers Pharmaceutical care Poison control center Pharmacy Council of India Polymerase chain reaction Pharmacoeconomics

xvi

PET PharmD PhD PICO PK/PD PMC PMR PPR PPR PR PVPI QALY QD QID QOL QWB R&D RBC RCT REC RR SIP SMD SOAP TB TDD TDM TID U&EM UDD USA USFDA USP UTI Vd WHO WHOQOL

Abbreviations

Positron-emission tomography Doctor of Pharmacy course Doctor of Philosophy Patient, intervention, comparison, outcome Pharmacokinetic and pharmacodynamics PubMed Central Personal medication record Personal prescription record Pharmacy practice regulation Per rectum (by rectum) Pharmacovigilance Program of India Quality-adjusted life year Quaque die (once a day) Quater in die (four times a day) Quality of life Quality of well-being Research and development Red blood cells Randomized clinical trials Research ethics committee Relative risk Sickness impact profile Standardized mean difference Subjective, objective, assessment, and plan Tuberculosis Targeted drug delivery system Therapeutic drug monitoring Ter in die (three times a day) The urgent and emergency medicine Unit dose dispensing United States of America United States Food and Drug Administration United States Pharmacopeia Urinary tract infection Volume of distribution World Health Organization World Health Organization quality of life instruments

List of Figures

Fig. 1.1 Fig. 1.2 Fig. 2.1 Fig. 3.1 Fig. 3.2 Fig. 3.3 Fig. 4.1 Fig. 4.2 Fig. 4.3 Fig. 4.4 Fig. 5.1 Fig. 6.1 Fig. 7.1 Fig. 7.2 Fig. 7.3 Fig. 8.1 Fig. 8.2 Fig. 8.3 Fig. 9.1 Fig. 10.1 Fig. 11.1 Fig. 11.2 Fig. 11.3 Fig. 11.4 Fig. 12.1 Fig. 12.2 Fig. 14.1 Fig. 14.2 Fig. 16.1

Types of pharmacy . .. . . . . .. . . . . . .. . . . . .. . . . . . .. . . . . .. . . . . .. . . . . . .. . . . . Roles, responsibilities, and activity of pharmacist in healthcare delivery .. .. . .. .. . .. .. . .. .. . .. .. . .. .. . .. .. . .. .. .. . .. .. . .. .. . .. .. . .. .. . .. . Systematic approach for pharmaceutical care . . .. . . . . . . .. . . . . . . .. . . . Clinical pharmacy requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Role and responsibility of clinical pharmacist . . . . . . . . . . . . . . . . . . . . . . Function of hospital pharmacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medication errors . .. . .. .. . .. . .. .. . .. . .. .. . .. .. . .. . .. .. . .. . .. .. . .. . .. .. . Medication error prevention . . . . .. . . . . . . . . .. . . . . . . . . .. . . . . . . . . .. . . . . . . Echo model for health outcomes . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . Health outcomes (clinical, economic, and humanistic) and sources of HEOR evidence . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . Communication model . . .. . .. . . .. . .. . . .. . . .. . .. . . .. . .. . . .. . .. . . .. . . .. . Pharmaceutical care interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Workflow of DIC using evidence-based medicine approach . . . . . . Schematic diagram of patient and health consumes with stakeholders . . . .. . . .. . .. . . .. . .. . . .. . .. . . .. . . .. . .. . . .. . .. . . .. . .. . . .. . . .. . Relationship between plasma concentrations and therapeutic outcomes . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Layout design of an ideal community pharmacy . . . . . . . . . . . . . . . . . . . Process of home medication review (HMR) . . . . . . . . . . . . . . . . . . . . . . . . Diet and exercise chart . .. . .. . .. . .. . .. . .. . .. . .. . .. .. . .. . .. . .. . .. . .. . .. . Organization of hospital pharmacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Movement of allopathic drugs from wholesaler to patients . . . . . . . How to detect the ADRs .. .. . .. . .. .. . .. . .. . .. .. . .. . .. .. . .. . .. .. . .. . .. . How to report the ADRs .. .. . .. . .. .. . .. . .. . .. .. . .. . .. .. . .. . .. .. . .. . .. . The flowchart of pharmacovigilance systems . . . . . . . . . .. . . . . . . . . . . . . Geriatric patients at risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of MTM learning by MirixaPro . . . . . . . . . . . . . . . . . . . . . . . . . . The framework of drug therapy management . . . . . . . . . . . . . . . . . . . . . . Clinical pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a and b) Graphical presentation of half-life . . . . . . . . . . . . . . . . . . . . . . . . Clinical product development phases . .. . . .. . .. . .. . . .. . .. . . .. . .. . .. . .

5 7 23 34 35 35 53 54 55 55 65 77 88 100 103 113 118 139 146 168 191 191 192 195 223 226 248 252 266 xvii

xviii

Fig. 17.1 Fig. 17.2 Fig. 18.1 Fig. 18.2 Fig. 18.3 Fig. 20.1 Fig. 20.2

List of Figures

Personalized medicines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Concept of genetic polymorphism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality-of-life (QOL) domains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SQOL factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Application of QOL instruments . . . .. . . . .. . . . .. . . . .. . . . .. . . .. . . . .. . . . Forest plot (blobbogram) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Combining all the studies of the forest plot . . . . . . . . . . . . .. . . . . . . . . . . .

280 284 300 301 302 324 325

List of Tables

Table 2.1 Table 2.2 Table 4.1 Table 4.2 Table 6.1 Table 6.2 Table 6.3 Table 6.4 Table 7.1 Table 7.2 Table 7.3 Table 7.4 Table 7.5 Table 8.1 Table 8.2 Table 8.3

Table 10.1 Table 10.2 Table 10.3 Table 11.1 Table 11.2 Table 11.3 Table 11.4 Table 11.5 Table 11.6

Urgent and emergency medicines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . An overview of the pharmaceutical care process . . . . . . . . . . . . . . . Commonly abused OTC drugs as self-medication by patients and health consumers . . .. . . . . .. . . . .. . . . . .. . . . . .. . . . .. . . . . .. . . . .. . . . Look-alike and sound-alike names reported to the ISME MERP from July through September 2010 . . . . . . . . . . . . . . . . . . . . . . New dimension of service offered by pharmacist . . . . . . . . . . . . . . . Elements of pharmaceutical care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medication therapy problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Components of FARM and SOAP notes . . . . . . . . . . . . . . . . . . . . . . . . General guidelines while responding to drug information inquiry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Types of drug interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Absorption-based drug interaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Potential drug therapy problems to look in prescription analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . List of established TDM drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Home medication review questionnaire for type 2 diabetes mellitus with hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adverse drug reactions of oral anti-diabetes . . . . . . . . . . . . . . . . . . . . Minor ailments of eye accidents, infections, poor eyesight, dry eyes, night blindness, ear, otitis media, discharge, and deafness . . . .. . . .. . . .. . . .. . . .. . . . .. . . .. . . .. . . .. . . .. . . .. . . . .. . . .. . . .. . . The specimen oath of pharmacist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Organizational chart of drug administration . . . . . . . . . . . . . . . . . . . . . Discrepancy in medicine prices in Indian market . . . . . . . . . . . . . . . Therapeutic drugs causing serious hazards to the public . . . . . . . Drug-induced toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Genotoxicity of prescription drugs in animals . . . . . . . . . . . . . . . . . . Resources commonly used in pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . Examples of the prescribing cascade in the elderly patients . . . Examples of drug-food interactions in the elderly patients . .. . .

21 22 43 47 79 82 84 85 92 98 100 102 104 120 120

122 163 168 177 186 186 190 194 197 197

xix

xx

Table 11.7 Table 11.8 Table 11.9 Table 11.10 Table 11.11 Table 13.1 Table 15.1 Table 18.1 Table 18.2 Table 18.3 Table 19.1

Table 19.2

List of Tables

Examples of drug-disease interactions in the elderly patients .. . .. . . .. . .. . . .. . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . .. . . Examples of important drug interactions in the elderly patients .. . .. . . .. . .. . . .. . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . .. . . Phases of embryonic and fetal development . . . . . . . . . . . . . . . . . . . . Nonpharmacological and pharmacological recommendation for various conditions in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oncology pharmacist practice and drug-specific interventions . . .. . . .. . . .. . . .. . . .. . . .. . .. . . .. . . .. . . .. . . .. . . .. . .. . . .. . . Brand medicines with example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Examples of some biotherapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Example of a cost-consequence table . . . . . . . . . . . . . . . . . . . . . . . . . . . . Example of generic instrument . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Example for disease-specific QOL instruments . . . . . . . . . . . . . . . . . Therapeutic drugs causing serious hazards to the public health (https://www.who.int/medicines/areas/quality_safety/ safety_efficacy/Pharmacovigilance_B.pdf) . . . . . . . . . . . . . . . . . . . . . . Drug-induced toxicity (Guengerich 2011) . . . . . . . . . . . . . . . . . . . . . . .

197 197 199 202 212 240 259 290 298 299

317 317

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and Hospital Pharmacy A. N. Nagappa and Vaishnavi Naik

Abstract

The historical preview of health sciences and technology had a great impact on human existence. Drug discovery and development and how the drugs are being handled in a society are two different domains of pharmacy. A brief history of advent of pharmacy profession is being discussed here to give a clarification for readers. The evolution of pharmacy from manufacturing to patient-centric care path explains the multiple role of pharmacist. Keywords

Pharmaceutical industry · Community pharmacy · Clinical pharmacy · Hospital pharmacy · Drug safety · Drug efficacy and patient care

1.1

Introduction

The medieval apothecary was the ancestor of the pharmacy industry, community pharmacy, clinical pharmacy, and hospital pharmacy. In Europe individuals selling wine, spices, and herbs were known as Apothecaries. They prepared and sold medicines to physicians and patients directly. In addition, they offered medical advice and patient counselling. The Apothecaries engaged themselves in identifying the diseases in a patient, making the medicine, and administering them with a skill of following the prognosis of the disease. The patients seeking medical advice and tips

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_1

1

2

A. N. Nagappa and V. Naik

for management of the diseases received counselling from apothecary. In due course it became practically impossible to provide satisfactory guidance to the patients which resulted in bifurcation of healthcare system into physician, nurse, and pharmacist. The healthcare activity of identifying the disease in a patient and writing prescriptions of medicines was practiced by the doctors or physicians initially. Extemporaneous preparation of the medicines from chemicals and natural products was carried out by pharmacists, and nurses developed expertise in healthcare services which satisfied the patients. They also become experts in drug administration as per the prescriptions written by the doctors or physicians. As the time passed, the health care team realized the importance of collaborative healthcare teamwork (Scahill et al. 2017). Initially the pharmacists were engaged in preparing tablets, capsules, and liquid orals from chemicals and natural products suitable for patients for consumption. Doctors predominantly engaged themselves in diagnosis with a comprehensive background of human anatomy, pathophysiology, clinical microbiology, and pharmacology. The pharmacists were engaged in pharmaceutical services such as dose calculations, adverse drug reactions, review of the treatment, and looking into the patient safety aspects. Nurses were engaged in attending the inpatients’ needs and providing the feedback to the doctors about the patients admitted to the hospital. Hence the doctor, pharmacist, and nurse became the core healthcare providers who became responsible for providing comprehensive healthcare delivery (Hepler and Strand 1990; Van Mil and Schulz 2006). The professionals who provide health care services are called clinicians. The clinicians are supposed to work like a team and are required to provide elaborative patient care. They have to appreciate each other’s expertise, clinical skills, and aim at providing the best possible care to the patient. The communications among doctors, pharmacist, and nurses should be professional and without any barrier. The equality among clinicians is a basic requirement to provide quality healthcare to the patients. The mutual respect and appreciation of role of fellow clinicians are essential for establishing a rational healthcare system and to provide evidence-based healthcare. The new trend of pharmacy services is bifurcated into industries, community pharmacy, hospital pharmacy, and clinical pharmacy based on the nature of the services. Pharma industries are responsible for making quality and safe formulations of medicines. Community pharmacy is an independent and chain pharmacy, which is mainly engaged in patient counselling and pharmaceutical care along with dispensing for the given prescription by the Physicians. Hospital pharmacy is located in the hospital and provides the medicinal needs of hospital inpatients. Clinical pharmacist works in hospital as a team helping the doctors, nurses, and patients with drug information and provides inputs regarding rational use of medicines (Berenguer et al. 2004). The medicines are essential inputs in order to control disease and gives relief from disease morbidities in patients. They are lifesaving and prevent complications of the disease of the patient. There are continuous efforts by scientists and pharmaceutical industry to provide effective, safe, and quality medicines to patients in mitigating the complications (morbidity) and preventing from death (mortality). Pharmacists are

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and. . .

3

part of research and development team who engage in research and development activity by which new drugs are found out and are used in making new medicines for the diseases; for example, the diseases like Alzheimer, cancer, dengue, chikungunya, and Ebola are on high research priority. The pharma industries have grown into big corporates over a period of time into multibillion industries with very much sophisticated and advanced technology. They are engaged in catering the needs of healthcare by making availability of quality medicines. Although pharma industries are driven by intellectual proprietary rights, there is a high peer competitive practice. The stakes in pharma industry are very high with great risk of failure in drug discovery and development. The volume of investments is huge with no guarantee of success. Even after getting approval from regulators, they have to invest good amount of money to develop and sustain leadership in market. The pharmaceutical market is highly regulated by various law and regulations which is highly complicated. The manufactured products are likely to expire and industries should manage the product sale before the date of expire. In the developing countries, the unethical marketing practices are rampant leading to irrational use of drug by the prescriber and self-medication practices by the patients. Despite having adequate regulation, the implementations of regulations have received lackadaisical approach by the regulators and other stake holders like pharmaceuticals industries, doctors, pharmacists, patient, and health consumers. They are having the opinion that the drugs sold in the pharmacies by the pharmacist are safe and does not cause any serious harm. This negligence is the main input for self-medication. Drugs of all kind are purchased in the open market due to poor regulatory environment. Added to this rigorous marketing practices has let to uncontrolled sale of prescription medicine. Pharma profession and industries are regulated by respective Government authorities. With various rules and regulations to safeguard the patient with the help of pharmacy practice. Pharmacists are having major role in public health apart from industrial practices and research. Pharmacists are supposed to register in the pharmacy council of respective countries. In India, the qualified pharmacists are supposed to register in Pharmacy Council of India. Pharmacy Council of India issues certificate of registration, which they have to produce on demand by regulators, Patient and Health consumers (P&HC). No body other than pharmacist is allowed to provide pharmaceutical services to public. Pharmacists are supposed to maintain and uphold professional dignity and decorum so that the public shall recognize identity and consult qualified pharmacist for the drug-related problems and health education. Pharmacists are supposed to be custodian of prescription medicine and are not to allow and free access to prescribe medicine to public in large amount. Pharmacists are not supposed to diagnose and prescribe medicines to a patient on their own. They must dispense meticulously the medicines on a prescription written by registered medical practitioner. While dispensing prescribed medicine, pharmacist should use his technical skills in identifying any major discrepancy in the prescription and alert the doctor without the knowledge of the patient. This is very important because the patient may get scared and change the opinion regarding the doctor. Hence pharmacists are not supposed to openly criticize doctor or his prescription in front

4

A. N. Nagappa and V. Naik

of the patient. Pharmacist should also investigate the prescribed medicine and try to identify the side effects of drugs like drowsiness, sleep disturbances, or any such changes drug is likely to cause in patient. The act of dispensing means the pharmacist will take complete details of drugs, doses, adverse effects, outcomes, and special instructions being explained while handling over the medicines to the patients. The pharmacists service should be delivered with compassion. The patient should feel the sense of respect and gratitude towards the pharmacist. The pharmacist shall feel accomplished with satisfaction that he has provided a quality service to the patient and helped him. The objective of pharmacist service is to provide patient safety by avoiding the major risk and events while using the prescribed medicines (Scahill et al. 2009).

1.2

Pharmaceutical Industry

Pharmaceutical industry has been well established in developed and developing countries; for example, the research and development work are dominant in developed countries, whereas active pharmacy ingredient manufacture and formulation of medicines are major activities in developing countries, especially in India and China. Pharmaceutical industry offers large number of job opportunities worldwide for pharmacist and non-pharmacist as well. The pharma industries have segments like research, development, production, quality control, marketing, and sales. Recently, due to expansion of pharma industry in IPR, pharmacovigilance and drug safety are also providing large job opportunities. Further due to opportunity or generic medicines and bio-similar lot of Indian companies are exporting the medicines to developed countries and earning sizeable foreign exchange (Garg et al. 2013).

1.3

Community Pharmacy

The community pharmacy is an organization where dispensing of prescription medicine is carried out by the community pharmacist. Community pharmacies are either proprietary pharmacies or chain pharmacies. Community pharmacies are usually located near public places like bus stand, railway station, or marketplaces. Community pharmacies are established in malls and in a hospital or nursing home. The criteria for all location are based on consumer’s accessibility for catching the maximum customers. Community pharmacies are supposed to procure stock of medicines from wholesalers, company’s depot, and clearing and forwarding agents. Prescription medicines are classified as schedule C&C1 (Biological) and schedule X (narcotic drugs). Medicines having alcohol as base which are prescribed for cough and cold are likely to be abused for recreational purposes. It is the responsibility of the pharmacist to control and prevent cough syrups being misused as alcoholic preparation (Mossialos et al. 2015). In developing countries community pharmacists have an acquired special status as a healthcare provider by involvement of patient and health consumer diseases

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and. . .

5

management. Apart from dispensing community pharmacists engage in maintaining electronic health records. The electronic health records of individual’s patients are used for providing pharmaceutical care. Electronic health records are source of information about patient medical history, disease status, medication history, drug allergy, and any other classified specific information of the patients. Pharmacist can share this information with doctors and nurses in order to provide rational healthcare. The pharmacist is supposed to maintain confidentiality of the patient’s condition and prescription (Goode et al. 2019).

1.4

Hospital Pharmacy

The hospital pharmacies are located within the hospital premises and are integral part of hospital itself as shown in Fig. 1.1. The hospital pharmacy services include compounding of medicines drug store management ward pharmacy management. Hospital pharmacies are also established central pharmacy, satellite pharmacy, and oncology pharmacy. Hospital pharmacy services also include establishment of hospital formulary, drug therapy management, and bulk manufacture of formulation to be used for hospital patients. They are also consulted by doctors and nurses regarding the information of drug dose, storage conditions, and drug and poison information. These services are imperative when there is no clinical pharmacist in the hospital (Barrett et al. 2016; Tomasulo and Silverman 1978).

Fig. 1.1 Types of pharmacy

6

1.5

A. N. Nagappa and V. Naik

Clinical Pharmacy

Clinical pharmacists are responsible for assisting the doctors and nurses in the matter of drug information. They are the members of ward round team wherein they observe the patient and asses the patients’ conditions in terms of drug-related aspect. They are supposed to inform physician regarding symptoms of under/over dose of medicines, adverse drug reactions symptoms, and the improvement which are going to create harmful developments in patient’s conditions. The clinical pharmacist duties include checking the prescription and work on medication review, checking of drug/food interactions appropriateness of medicines doses and guidelines for drug administrations (Thomas et al. 2019). The clinical pharmacist has to work in collaboration with doctor and nurses and also improve the therapy of the patients by cost following the patient conditions. For achieving this, clinical pharmacist should go forward rounds accompanied by fellow clinical pharmacist and intern pharmacist. Clinical pharmacist is also responsible for establishing pharmaceutical care services, pharmacovigilance services, drug- drug/ food interactions, and drug/poison information services. A clinical pharmacist is entitled to publish hospital bulletins, hospital formulary, and standard treatment guidelines in consultations with doctors and nurses and make sure other healthcare professionals are aware of the updated information about the drugs (Shrestha et al. 2020).

1.5.1

Roles and Responsibilities of Pharmacist

The roles and responsibilities of pharmacist is shown in Fig. 1.2. Among healthcare professionals, pharmacist is known as medicine man who works closely with other healthcare professionals in the matter of medicines. They have the knowledge about chemistry of drugs and are responsible for prevention of drug inflicted injuries in the patients. Every drug has a profile of adverse drug reactions and there are so many conditions to be met to optimize drug uses in patients. Drugs in the alphabetical order from Aspirin to Zidovudine are unique in their actions in an individual patient. Each drug produces similar qualitative effect but differs quantitatively at different dose concentrations. While using these drugs if there is negligence or lackadaisical approach there is a possibility of patient being harmed seriously, damaging the vital organs like kidney, liver, heart, and brain. Usually, drugs are administered more than required so that the consequence of a drug effect is uncertain. The drug administered is carried throughout the body by the blood to each receptors, cells, tissues, and organs. Drugs are being biochemically capable of producing its effect on cells when it comes in contact with it. Usually, drug is required when there is a damage to the organs by the disease. Hence, it is described when drug reaches the target receptors or organs after administrations. It is described like drug being on a random walk. The drug which is not acting on the target receptors but travelling in the blood freely is the culprit causing side effects, toxic effects, and adverse drug reactions. It is necessary to

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and. . .

7

Fig. 1.2 Roles, responsibilities, and activity of pharmacist in healthcare delivery

administer extra dose rationally which helps a fraction of administered drug to produce its action (Kehrer et al. 2013). It is a challenge for the pharmacist to focus on drug effect and minimize side effects and adverse drug reactions. For this, pharmacist should develop special skills and knowledge which he/she should apply to get outcomes of patient’s safety. Pharmacists can develop formulations of selected drugs as targeted drug delivery system (TDD). TTD is like guided information to reach their site of action and produce its effect. There is no need to administer extra drug to reach its target like in conventional dosage form. For example, in treatment of asthma, steroids and bronchodilators (like salbutamol) are administered to the lungs directly instead of orally. They are administered by using inhaler device for asthma and COPD medicines manually actuated pressurized metered-dose inhalers conventional puffer. Advantage of administration of medicines by inhalations to patients is to get freedom from ADR of steroids and salbutamol. The requirement of drug also gets reduced and its cost as well. Pharmacists are also responsible to provide quality medicines at affordable price to all the patients. Although pharmacists have little control over the price of the medicine available. However, they can use their knowledge in bringing down the cost of medicines by their technical knowledge and skill. It is well known to all pharmacist that medicines available in the market must and should be officially standard of the pharmacopeia. This being the legal requirement and all medicines

8

A. N. Nagappa and V. Naik

having similar composition should be substitute for each other are likely to be producing same effects. Hence pharmacist can suggest a doctor to allow him to substitute low-cost medicines instead of high-cost prescribed medicines. However, in practice it is observed the doctors rarely agree to substitute in the interest of the patients. For example, Paracetamol IP is available in the several brand names; there are 793 brands which has content of Paracetamol IP as the core content, for example, Calpol tablet, Paracetamol IP manufactured by MNC costs 65/ Rupees for 15 tablets. The same Paracetamol tablet is available for Rupees 7/ only in Jan Aushadhi Kendra. Like this we can find large differences in medicine prices of therapeutic categories. It is very much essential for a pharmacist to be optimal to the medicine’s prices. He/she should never give up efforts to help needy patients as for expenditure on medicines is concerned. If this activity cost-effectiveness is continuously done, he/she may be able to convince doctors, hospital authorities, and patients in reducing the cost of prescription medicines (Sinha 2014). Pharmacists are projected as drug consultants who are approached by doctors, nurses, and other healthcare professionals. They are supposed to give opinion about medicines prescribed and its importance in therapeutic effectiveness. Pharmacists are engaged thoroughly are involved in healthcare delivery and have acquired an expertise in drug disease and healthy lifestyles. In community pharmacy pharmacists are the professional who must decide whether the patient can be treated for minor element or he/she referred to higher consultations. P&HC approaches pharmacist in the matter of minor ailments, weight management, contraceptive information, hygiene, and any other matter which do not mandate consultations with a doctor. Doctors being busy and available in less number for consultation they are overburdened with workload; in such circumstances, pharmacists are very helpful to both doctors and P&HC who can treat a minor element or refer a serious condition in a patient for consultation with the doctor. Pharmacist being available for consultation in the pharmacy, the P&HC can have an easy accessibility to pharmacist. In order to formulize the interactions, there should be a provision for consultation room wherein the patient and pharmacist sit across a table to discuss health issue. The pharmacist makes notes of patient discussion and tries to formulate customized patient education plan which consist of various advises. The patient after clarifying his doublet regarding disease, drug, and lifestyle leaves the consultation room with relief from stress. This kind of service is going to build confidence in pharmacist and sustain goodwill for future. Pharmacists are having peer competence for quality services and compete among themselves to get maximum prescriptions. In this process they should not be indulged in unethically practices like offering discounts on purchase of medicines, etc. In order to excel in pharmacy practice profession they should adopt guidelines recommended by FIP star pharmacist. The patients and health consumers in India are facing the challenges of disease/ health management with limited professional healthcare provider assistance. The patients who solely depend on healthcare professionals in matter management of disease or health face the crisis of shortage of healthcare professionals. To fill the gap and taking advantage of the opportunity many quacks have become healthcare

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and. . .

9

providers who are empirically treating patients with all kind of modern medicines across the country. They are posing the public to the unprecedented risk of druginduced injuries by irrational use. These practices are rampant in villages and urban slums. The lack of implementing the vigilance by professional regulatory bodies. These practices are mushrooming in the clinics run by quacks. There is a pressure by the public on government to put end to quackery and streamline the healthcare delivery, which is transparent, accountable, and cost effective. See Fig. 1.2 for roles, responsibilities, and activity of pharmacist in healthcare delivery. The modern healthcare system is a practice based on knowledge which demands expertise of physicians, pharmacists, and nurses with latest development in their profession. The continuous education program and periodical licensing examinations to ensure the quality of services are going to be the norms like in developed countries. All this has become feasible due to information and mobile technologies have become handy and accessible for the healthcare practice. However, the professional background is mandatory as the professionals’ background of each healthcare service is focused on unique area. For example, physicians are experts in diagnosis and are not experts in pharmaceutical sciences, similarly pharmacists are not experts in nursing sciences. Hence the WHO is advocating alliance for healthcare professionals in the interest of patients. The team effort can only lead to the practice of evidence-based medicine, rational use of drugs, and quality use of medicine leading to optimized patient safety and efficacy. In India, the physicians are involved in the pharmaceutical industry are engaged in promotion of medicine with a pretext of education the physicians regarding pharmaceuticals. But in India, the pharmacist, although an expert in pharmaceutical sciences, is out of the patients care and does not practice clinical pharmacy. This kind of scenario has led to the doctor centric and product centric healthcare which has limited outcomes and a major cause for patient discontent with the healthcare provided (Olatunde et al. 2010). There are several issues and interventions by pharmacist in order to make the outcomes as expected. The pharmaceutical care (PC), medication therapy management (MTM) and home medication review (HMR) are some of the popular services which have earned special status for pharmacist in the USA and Canada. These services can be implemented in our country only after implementing the core reforms and regulations. The first and foremost thing which need to be implemented is regarding healthcare provision is a national facility of documentation of prescription and dissemination of the data in public domain. This will identify and check whether the prescriber is a genuine registered medical practitioner or quack or is he trained in Ayurveda and prescribing allopathic medicine. This can be achieved by extracting the data from dispensing counters. After curbing the irrational prescribing, the next stage is to promote team-based health practices. Currently the drug stores are managed as a family business rather than a professional practice. The community pharmacy is solely dependent on volume if trade for its profits. The traditional role of Community Pharmacist the community pharmacy based services of patients although very common in developed countries, is unheard and totally new to our country. The community services like patients’ education,

10

A. N. Nagappa and V. Naik

counseling, will enhance the value of treatments. The services of monitoring hypertension, obesity, monitoring the anti-platelet/thrombolytic therapy and diabetes will reduce the burden on physicians. Daily tasks undertaken by community pharmacists include clinical scrutiny of prescriptions and oversight of safe dispensing processes. Providing patients with advice about medicines, treatment and public provision of public health information to patients and customers and promotion of wellness, signposting people to other services, self-care organizations or information resources, assessment and treatment for minor ailments, professional oversight of the sales of over the counter (OTG) medicines, Informing the patients and guiding them reporting the safe use of OTC medicines is called informed self-medication practice liaison with other healthcare professionals, Medicines management support for physicians practices includes supporting practice formulary and clinical guideline implementation, repeat prescription management. Modernization of community pharmacy is the expectation of the patient and health consumer in the country as revealed in survey conducted by India Today. The wish list of health consumers included emergency out of hour’s services to provide special medicines for the terminally ill, emergency hormonal contraception services to reduce the incidence of unwanted teenage pregnancy, smoking cessation services and minor ailments service. The medicine prices in the country are another burning issue haunting the healthcare sector. Prices of the essential list medicine in our country are regulated by drug price control order. Recently the central government has finalized the pharma pricing policy for 348 essential drugs. These drugs will come under price control of the government, with an average price reduction of 11 percent. It has committed to reducing prices of essential drugs including anti-diabetics, painkillers, anti-infective and anti-cancer drugs. The government also has come out with Jan Aushadhi generic medicine outlets to promote the use of generic medicine in clinical practice to reduce the cost of therapy. The brand medicines are expensive but still used due to lack of awareness and vigorous marketing practices by the pharma industry. There are nearly 1 lakh brands of medicine manufactured by 40 thousand large, medium, and small manufacturers. Unfortunately, in our country, the pharmaceutical sector lies with ministry of fertilizers and chemicals instead of ministry of health. The anomalies in administration setup are causing the hindrance in modernization of community pharmacy. There is need to set right these obstructions to begin the modernization of healthcare services (Mahatme et al. 2012). The doctor of pharmacy course (Pharm D) has begun in India, and the regular first batch is going to come out in 2014. There is lot of confusion among the students, about their carrier perspectives. In south India it is getting popular. First time in India, we are seeing the pharmacists in the clinics. Although initially there was skepticism about the role and duties of clinical pharmacist, it is heartening to learn our physicians are accepting the pharmacists in hospitals. They are appreciating the pharmacist contributions which not only are improving the quality of outcomes and their assistance is reducing their work burden. The physicians welcome the pharmacists as they intend to compliment but not to compete with them

1

Introduction: Pharmacy Industry, Community Pharmacy, Clinical Pharmacy, and. . .

11

professionally. In years to come days are not for. Where clinical pharmacy practice become essential services in hospitals like in any other developed country. The government of India has announced economic reform by opening the doors for foreign direct investment in retail business. The Indian retail sector is roughly estimated at over $500 billion (Rs 27.5 lakh crore). The community pharmacy is one of the important components of most of the retail chains in India. There is a speculation that chain pharmacies like Walgreens, CVS, Wal-Mart, and Kroger are interested to open their operations and establish in India. The chain pharmacy in India will have a detrimental effect on conventional drug store, as these will compete for more healthcare-related business by providing services. Due to competition,the conventional retail trade should also adopt and modernize as the stage is set for better services instead of just dispensing. It can be hoped that retail pharmacy in India is set for modernization. The change is inevitable as knowledge, attitude, and practice are becoming critical in influencing the disease morbidity and mortality. It is not just the medicines alone, but the lifestyle and motivation of the patients to participate in the therapy on long term is very imperative. For example, the disease conditions like diabetes mellitus and hypertension needs to be managed meticulously. There is a need for continuous monitoring of the disease lifelong. Unfortunately, current model of healthcare focuses on critical conditions but not on patients in the community at large. There is an evidence regarding importance of control of the disease as prevention approach. There is huge savings on medical expenses as many casualties due to exacerbations of the condition are avoided. This would also save money for the exchequer due to fewer incidences. We can expect in future there is hope that healthcare provision will become more effective and safer.

1.6

Conclusions

Medicines are essential component for treatment of disease. Medicines should have properties, consistency in action demands exclusive environment during storage. They should be prescribed by a doctor and dispensed by a pharmacist. Medicines do not produce effectiveness without proper route of administration, following administration they need to be used under the direction of registered doctor, nurse, and pharmacist. There is a need to observe the patients during treatment for drug allergies and adverse drug reaction. The involvement of pharmacist from the point of manufacturer till the dispensing provides huge scope for employment and service. Hence pharmacy profession is manifested in various manners throughout the healthcare delivery.

References Barrett A, Helwig M, Neves K (2016) Mapping the literature of hospital pharmacy. J Med Lib Assoc 104(2):118–124. https://doi.org/10.3163/15365050.104.2.005

12

A. N. Nagappa and V. Naik

Berenguer B, La Casa C, de La Matta M, Martin-Calero M (2004) Pharmaceutical care: past, present and future. Curr Pharm Design 10(31):3931–3946 Garg S, Hasan R, Scahill S, Babar ZU-D (2013) Investigating inspection practices of pharmaceutical manufacturing facilities in selected Arab countries: views of inspectors and pharmaceutical industry employees. East Mediterr Health J 19(11):919–929 Goode JV, Owen J, Page A, Gatewood S (2019) Community-based pharmacy practice innovation and the role of the community-based pharmacist practitioner in the United States. Pharmacy 7(3):106 Hepler CD, Strand LM (1990) Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm 47(3):533–543 Kehrer JP, Eberhart G, Wing M, Horon K (2013) Pharmacy's role in a modern health continuum. Canadian Pharm J 146(6):321–324. https://doi.org/10.1177/1715163513506370 Mahatme M, Dakhale G, Hiware S, Shinde A, Salve A (2012) Medical store management: an integrated economic analysis of a tertiary care hospital in Central India. J Young Pharm 4(2): 114–118. https://doi.org/10.4103/0975-1483.96626 Mossialos E, Courtin E, Naci H, Benrimoj S, Bouvy M, Farris K, Noyce P, Sketris I (2015) From “retailers” to health care providers: transforming the role of community pharmacists in chronic disease management. Health Policy 119:628–639. https://doi.org/10.1016/j.healthpol.2015. 02.007 Olatunde S, Boon H, Hirschkorn K, Welsh S, Bajcar J (2010) Roles and responsibilities of pharmacists with respect to natural health products: key informant interviews. Res Social Adm Pharm 6(1):63–69. https://doi.org/10.1016/j.sapharm.2009.02.004 Scahill S, Harrison J, Sheridan J (2009) The ABC of New Zealand’s ten year vision for pharmacists: awareness, barriers and consultation. Int J Pharm Pract 17(3):135–142 Scahill SL, Atif M, Babar ZU (2017) Defining pharmacy and its practice: a conceptual model for an international audience. Integr Pharm Res Pract 6:121–129. https://doi.org/10.2147/IPRP. S124866 Shrestha S, Shakya D, Palaian S (2020) Clinical pharmacy education and practice in Nepal: a glimpse into present challenges and potential solutions. Adv Med Educ Pract 11:541–548. https://doi.org/10.2147/AMEP.S257351 Sinha HK (2014) Role of pharmacists in retailing of drugs. J Adv Pharm Technol Res 5(3):107. https://doi.org/10.4103/2231-4040.137383 Thomas D, Marriott J, Vadlamudi R, Efendie B, Maine LL (2019) Introduction to clinical practice, research, and pharmacy education. In: Thomas D (ed) Clinical pharmacy education, practice and research. Elsevier, Amsterdam, pp 1–9 Tomasulo WJ, Silverman C (1978) Core references for the hospital pharmacy library. Hosp Formul 13:793–794 Van Mil J, Schulz M (2006) A review of pharmaceutical care in community pharmacy in Europe. Harvard Health Pol Rev 7(1):155–168

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare Delivery A. N. Nagappa and Vaishnavi Naik

Abstract

Healthcare services are vital and complex. The diagnosis and prescribing are the domain of doctors and nurses who are supposed to provide nursing and administration of prescribed medications to the inpatient in the hospital. Pharmacists are supposed to dispense the prescribed medications for the outpatient in the community. There are several occasions of interaction and consultation among doctors, nurses, and pharmacists who are also engaged in patient counseling with an objective to ensure safe and effective treatments. Collaborative healthcare is very imperative in patient safety. Keywords

Community pharmacist · Academic clinical pharmacist · Hospital pharmacist · Military pharmacist · Retail pharmacist · Veterinary pharmacist

2.1

Pharmacy Profession

The profession of pharmacy along with duties and obligations is usually bound by professional ethics. The practice of ethics can only build the professional image of pharmacy profession. The ethics are guidelines for directing the professional practice in case of dilemma while practicing profession. The profession is meant for the commitment of service to the customers, for example, mother’s commitment to

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_2

13

14

A. N. Nagappa and V. Naik

child, wherein mother dedicates and serves her child unconditionally as she is bound physically, mentally, and emotionally. The professional of pharmacy is also standing on such guidelines, which are called ethics of pharmacy profession. There is another chapter on ethics and professional practice in other chapter of this book, which elaborates the relationship between ethics and pharmacy. Profession with its ethics is a paid occupation basically which involves prolonged training with a formal qualification. It is any type of work that needs special training or a skill, which also accompanies respect, because it involves a high level of education. Pharmacy profession involves a mixture of both science and technology of preparing and dispensing medicines to patients. It is a healthcare profession that links health sciences with chemical sciences and aims to achieve the drug safety and efficacy while using the medicines. Pharmacy professionals are also known as pharmacist, chemist, druggist, apothecary, posologist, and clinical pharmacologist. The professional activities of pharmacist involve healthcare and chemical science application. The qualifications of pharmacist include PharmD, Master of Pharmacy, Bachelor of Pharmacy, and Diploma of Pharmacy. The related occupations of pharmacist include clinical pharmacologist, pharma technicians, pharmacy assistants/aides, clinical pharmacist, hospital pharmacist, community pharmacist, drug safety associates, clinical research coordinator, and compounder (Toklu and Hussain 2013). The scope of pharmacy practice has a traditional historical role as compounding and dispensing of drugs. In recent times pharmacy profession has also merged in healthcare delivery, wherein clinical pharmacists are to provide services such as reviving the prescription so that the patients are ensured with safety and efficacy during treatment. They also provide the drug information to fellow healthcare professionals along with patient and healthcare professionals. The modern pharmacist is not only the expert on drug therapy but also emerged as primary healthcare professional, who can optimize the use of medicines for the benefits of patient and health consumer. In the USA pharmacy practice is very much popular because of support by health insurance providers and government. Health insurance providers appoint a qualified pharmacist to check the duplication of medicine, generic medicine dispensing, and ADR in patients. To maximize their profits and business scope, they engage in drugstore and sell confectionaries, cosmetics, and stationaries along with hair-care products and magazines. They also have an outlet for farm fresh vegetables and fruits. The refreshment, Groceries, books, and coffee shops. This type of superstore chain with pharmacy engages in sale of merchandise and is popular in North America, Canada, and other developed countries (Stone 1998). Historically pharmacy profession has taken up the leadership in the discovery of medicines by exploring the herbal medicines and chemistry of natural products. This has led to the development of medicinal chemistry and pharmacology of medicinal products. Further pharmacists have become experts in making formulations and compounding into liquid orals, tablets, capsules, ointments, and injections. Pharmacy is primarily having five disciplines such as pharmaceutics, medicinal

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

15

chemistry, pharmacognosy, and pharmacology. Recently the new discipline, the fifth one, is pharmacy practice which blends the above five disciplines optimally to provide best practices of patient safety and efficacy of medicines. It is observed that there are no clear-cut boundaries between the above disciplines of pharmacy and basic health sciences like human anatomy, human physiology, human biochemistry, clinical microbiology, and biotechnology (Hattingh et al. 2009). The usual modus operandi includes other disciplines and professions like physicians and nurses as collaborative teams with pharmacist whenever they want to find out a new drug or new approach in patient care. They have a multidisciplinary team approach. One could observe here that pharmacy is neither a basic nor a biomedical science in a topical form; medicinal chemistry is a distinct discipline with a blend of synthetic organic chemistry, chemical biology, and pharmacology. Pharmacology is needed to study the pharmacy and has been taught to other healthcare profession like doctors and nurses. The pharmacist studies the pharmacology from biomedical science perspective and patient orientation, whereas doctors and nurses study pharmacology with a patient orientation emphasizing on therapeutics. The new discipline has emerged “pharmacoinformatic” combining drug discovery, drug development, drug efficacy, and drug safety. The World Health Statistics 2011 has given an estimate that there are 26 million pharmacists and pharmaceutical personnel who are working across the world. In 2020, it is estimated that it could exceed 30 million. Pharmacists are core healthcare professionals who are having a background, training, and education with a special focus on health outcomes. The pharmacist is capable of understanding the roles and responsibilities in a healthcare team, aiming at quality outcomes and quality use of medicines. The pharmacist who have established an chemist and druggist shops the small business establishments. It gives them a platform to practice pharmacy with their patients and health consumers. Optimization of drug treatment for an individual’s patient and health consumer has emerged naturally, where the pharmacist can explain about disease, drug, and lifestyle aspects to a patient. The patient needs to know and follow instructions to get relief from suffering due to disease. The Pharmacist who know about the Drug mode of action and metabolism along with pharmacological effect on the human systems can counsel the patient in an effective manner, which is often called as pharmacological and non-pharmacological treatment method in clinical pharmacy. Pharmacy profession varies from region to region in its presentation and style of functioning. However, it is bound by the International Pharmaceutical Federation (FIP). The annual conferences of FIP are the opportunities to exchange the advancement of professional practices. Trends in pharmacy profession are continuously changing from product orientation to patient centric. Nowadays the broad roles and responsibilities of a pharmacist are patient centric. In India also, gradually such changes are adopted slowly. The new regulations like introducing PharmD course and BS pharmacy operations and Pharmacy Practice Regulations 2015 are few examples (Dolovich et al. 2018). In India pharmacy profession is represented by the Indian Pharmaceutical Association (IPA) which was established in 1939. This is the premier association of

16

A. N. Nagappa and V. Naik

pharmaceutical professionals in India representing mainly pharmaceutical industry having 20 state branches and more than 50 local branches. Other Associations of Pharma industry are the Indian Drug Manufacturers’ Association (IDMA) and Organisation of Pharmaceutical Producers of India (OPPI) which are associations representing manufacturers of Indian and multinational companies. The Indian Pharmaceutical Association Congress was formed later, by combining other professional associations. Includes Pharma Industry from industries (IPA) regulation (Association of Drug Inspectors of India) APTI (Association of Pharmacy Teachers of India) IHPA (Indian Hospital Pharmacists of India), IPGA (Indian Pharmacy Graduates Association professionals IPAC has established affiliations with international Pharma professional association like International Pharmaceutical Federation (FIP), FAPA, CPA and AAPS. It also works with international bodies like the World Health Organization (WHO). There are other pharmacy associations including the AIOCD (All India Organisation of Chemists and Druggists) and ACPI (Association of Community Pharmacists of India). Internationally pharmacy profession is represented by the FIP, which the global federation is representing four million pharmacists and pharmaceutical scientists worldwide. All national organizations of pharmacy profession are represented in the FIP. The organizations like the IPA from India, the Royal Pharmaceutical Society of Great Brittan, the Pharmaceutical Society of Austria, the Canadian Pharmacists Association, and the American Pharmacists Association are members of the FIP (Tumkur et al. 2012; Hepler and Strand 1990). Pharmacy profession has developed the profession and has framed the code of ethics. They regulate the professional practice standards for their members. In developed countries like the USA, the Board of Pharmacy Specialties (BPS) is available for pharmacy practices. The BPS was established in 1976 as an autonomous division of the American Pharmacists Association. Today, BPS is the premier post-licensure certification agency worldwide that operates across the pharmacy profession to provide specialty certification to qualified pharmacists. Most importantly, BPS is above partisan interests and establishes independent, objective standards. The BPS certification is a voluntary process by which a pharmacist’s education, experience, knowledge, and skills in a practice area are confirmed as well beyond what is required for licensure to practice the profession. The board for cardiovascular diseases, infectious diseases, oncology, pharmacotherapy, geriatrics, nuclear pharmacy, nutrition, and psychiatry is available. Certification in Geriatric Pharmacy Practice is issued by Geriatric Pharmacy and Toxicology; the American Board of Toxicology certifies medical professionals and pharmacists in applied toxicology.

2.2

Role and Responsibility

The pharmacist plays an important role in healthcare delivery system as an expert in medicine and information regarding healthcare. The responsibility of pharmacist includes patient care, dispensing of medicines, prescription review, monitoring patient’s health, and checking the progress of health to optimize patient’s response

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

17

to medication therapy. The routine job of pharmacist includes dispensing of medications to patients as prescribed by the doctors. Patients consult the pharmacist to get information on prescribed medicine, disease, and lifestyle. Pharmacist after a face-to-face interaction with the patient corrects the patients and updates with uses of medicine, dose, side effects, adverse drug reaction, precautions, and contraindications. Pharmacist communicates directly with physician and nurse to ensure best practices (Anderson and Schumock 2009). In industries the pharmacist is involved in production, quality control, and quality assurance distribution detailing of the medicines along with marketing of the formulations. Industrial pharmacists are also engaged in drug discovery and development of safe and effective medicines. They are engaged in clinical research, drug development, clinical trials, supervising, production, quality testing, marketing, pharmacovigilance, and regulatory affairs. The carrier opportunities in pharmacy include pharmacy technicians, assistant pharmacists, and quality control inspectors. Academic pharmacist’s roles are to educate, train, evaluate, and develop pharmacy students/interns. Preregistration trainee pharmacists and other healthcare professionals also offer general support to students and are looked as role models and mentors. There are some academic teacher practitioners who work both in teaching and in hospital pharmacy/community pharmacy. They also engage in research like science-based area of practices, drug design, and pharmacy services. They are engaged in teaching, research, practicing, or a combination of all the three. They have an exciting career in universities in teaching and research area (Kehrer et al. 2013).

2.3

Clinical Academic Pharmacy

Clinical academic pharmacy combines clinical practice, teaching, and research roles bringing together the best advantage to the practitioner to provide evidence-based medicine. Clinical pharmacist who works in a traditional clinical setting like hospital or community pharmacy and undertaking research activities shall be bringing new dimensions to healthcare delivery. The patient and medical professionals healthcare workers are approaching the pharmacist in hospitals and drug stores to get the suggestions of pharmacist in the matters of treatment and prevention of overcoming the suffering due to diseases. Pharmacist needs to keep himself abreast with the latest developments in pharmacotherapy. Some of the professionals have blended the practice of community pharmacy with teaching. This service suits individual’s stand-alone practitioner providing pharmaceutical care for the patient’s either in clinic or home-based service. The advantage of this model is that the patient builds good relationship with the pharmacist and starts having trust about the pharmacist (Draugalis et al. 2006).

18

2.4

A. N. Nagappa and V. Naik

Community Pharmacist

Community pharmacists are considered as the public face of the profession. They work in their own pharmacies, local health centers, and chain pharmacies. Their includes Mainly helping the patient and health consumer and assessing their conditions, and guiding the patient and health consumer on what should they do to get back to good health and whether the patient is suffering from minor diseases or major health problem. The pharmacist should be able to judge which medicine should be given for minor ailment, for example, whether the patient is having cold, cough, allergy, hyperacidity, and loose motions. If the patient is having a major disease, then the patient should be referred to the hospitals or doctor consultant. The community pharmacist should be able to distinguish whether patient condition mandates hospitalizations or can be managed with OTC medications. Other responsibilities of community pharmacist are dispensing medicines written on receipt, patient counseling, inventory management, expiry goods surveillance, and many other activities (Deshpande et al. 2015). On receipt of a prescription pharmacist, he/she should read it carefully and make a care plan and advise the patient and health consumer with practical health tips. The pharmacist should act with responsibility. Community pharmacists enjoy special status and respect in their communities due to their services. Recently they are also engaging in such activities like management and monitoring of long-term conditions of asthma and diabetes. Pharmacists are licensed to provide vaccinations which was the traditional role of doctors. The vaccinations provided by pharmacists are cheaper for patient and healthcare consumer; also waiting time for vaccinations will be minimum as an added advantage.They also support patient and healthcare in smoking cessation and weight management and advise on sexual health. Community pharmacists can establish independent pharmacies or work in chain pharmacies. Community pharmacists have great order of progress and become senior pharmacy managers occupying the key roles in the chain pharmacies (Harm 2008).

2.5

Hospital Pharmacist

Hospital pharmacists have assumed an important role in healthcare team and are placed in government and corporate hospitals. They have different roles as a hospital pharmacist, for example, manufacturing medicines for the hospital consumptions, preparing the extemporaneous and customized medicinal formulations, testing the formulation for the quality, supplying the medicines to satellite pharmacy and ward pharmacy, and monitoring the effectiveness of medicines used in the hospitals, which is a special role of hospital pharmacist. They are also providing advice to fellow healthcare professionals along with patient and healthcare in the matter of dose, ADR, and formulary enquiry. They are responsible for developing standard treatment protocol and hospital formulary. Being in the vicinity of the hospital, they have emerged as specialist pharmacist in mental health, oncology, cardiology, pediatrics, and geriatric practice. The hospital pharmacist also works in ICU,

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

19

emergency medicine department, quality assurance, clinical trials, and drug information on medicine, gradually enter the management and teach the hospital staff, and work closer with doctors and nurses (Simpson 2017).

2.6

Military Pharmacist

Military pharmacist is supposed to work in the navy, army, and air force. They are commissioned officers with professional pharmacy training and undertake military training on assuming the role of military pharmacist. They are based in the army, navy, and air force camps or in the battlefields. They are responsible for seeing that medicines reach the point of dispensing in appropriate time. It is a challenging role where the military pharmacist works in highly stressed conditions where access to medicines and transportation is highly limited. At base camp they serve ex-service personnel and their families. They also provide service to ex-service personnel who may be suffering from injuries incurred during active service (Garcia et al. 1951).

2.7

Pharmacist in General Practice

General practices are the centers of medical practice established by government or private entrepreneur. They are also known as private hospitals, nursing homes, or consulting care centers and general practices. Pharmacists are helping the care delivery with their skills about medicines. They usually work as a part of team which makes a huge difference to both patients and healthcare professionals. They are usually in contact with patients directly and treat them under the supervision of doctors. They work with the doctors and nurses closely to resolve the issues with medicines which helps them to focus on skills which they need most. For example, the doctor may be able to focus on diagnosing and treating the patients, and issues of medicines are taken care by the pharmacist. They also engage in reviewing patient’s medicine and advise them on how to use it properly. General practice pharmacist can advise fellow healthcare professionals regarding medicines and issues arising while prescribing which reduces the prescribing errors (Ryan et al. 2018).

2.8

Pharmacist Working in Old-Age Homes, Hospice, and Senior Citizen Homes

Due to composite cities in urban living, senior citizen care homes are being established in big cities and metropolitan cities. Here older people with complex medical conditions live. The major issue with the geriatric patient is compliance with the medicines. Pharmacist must check and ensure the patients are being administered the right medicines with the right dose and in the right time. As the patients are living outside the hospital premises and in hospice or old-age homes, there must be an institutional support for the senior citizens. Pharmacist must involve in managing the

20

A. N. Nagappa and V. Naik

medicine supply stock and avoid waste. He must prepare a timetable and use a protocol to manage all the issues of medicine administration. He/she can use pillbox to simplify the medicine administration for the patients who suffer from dementia. Even in his absence, usually the pharmacist uses mobile app or artificial intelligence for simplifying the services to geriatric patients. The geriatric patients suffer from multiple conditions. They are on many medications to manage their conditions. Pharmacist in old-age home must resolve polypharmacy arising because large medicines are being used in patients. There are many minor ailments patients complain to the pharmacist. The pharmacist’s role is to work on these minor ailments and attempt to resolve the issues to the satisfaction of senior citizens. Pharmacist can provide services in a visiting mode (Wong et al. 2004).

2.9

Pharmacist Working in Urgent and Emergency Medicine (U&EM)

The main difference between emergency and urgency is that in emergency, there is immediate threat to life, health, property, or environment, whereas in urgency, there is no immediate danger or threat to life, health, property, or environment, but if not taken care in a given period, then the situation may turn to emergency. The urgent and emergency care settings are comprised of trauma hospitals, accident, and emergency department working centers and should be accessible from road usually at the entrance of the hospital and should be different from the main entrance and outpatient pharmacy. The urgent and emergency medicine services are provided by the pharmacist, when general physician surgeries and other healthcare service are not available (Table 2.1). The pharmacist is called upon to support patients with medicine-related issues along with treatment of common ailments. The pharmacist should have training in first aid and basic life support. As a pharmacist of urgent and emergency medicine setting, they provide access to lifesaving medicines which are listed below. Pharmacist in urgent and emergency medicine should be well versed in clinical skills for handling emergency situations and treating minor injuries, should be able to obtain a medicine history of the patients, and work closely with fellow healthcare professionals in the interest of patient welfare (Nichols et al. 2019).

2.10

Miscellaneous Urgent and Emergency Medicine

1. Water for injections: Remember if a patient is unconscious or is in very critical condition, then physicians do not prefer tablets, but they prescribe injectable drugs. 2. Diabetes: Glucagon injection 1 mg/mL, glucose solution 50%. 3. Gastrointestinal tract: Prochlorperazine—Injection 12.5 mg/mL, loperamide capsules 2 mg and Gaviscon tablets.

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

21

Table 2.1 Urgent and emergency medicines 1. Cardiac medicine • Aspirin tablets 300 mg • Atropine injection 600 micrograms/mL • Digoxin tablets 250 micrograms • Furosemide injection 50 mg/5 mL • Lidocaine 2%, 5 mL (100 mg bolus) • Glyceryl trinitrate spray • Tenecteplase vial • Dalteparin injection 4. Antibiotics • Amoxicillin capsules/co-amoxiclav tablets and suspension • Cefuroxime injection • Cefalexin capsules • Erythromycin tablets and mixture • Trimethoprim tablets • Metronidazole tablets • Penicillin V tablets • Benzylpenicillin injection 600 mg vial

2. Allergy • Hydrocortisone sodium succinate injection, 100 mg powder for reconstitution • Adrenaline 1 in 1000 (1 mg/ mL) • Chlorphenamine tablets 4 mg • Chlorphenamine injection 10 mg/mL

3. Pain management (Painkillers) • Paracetamol tablets 500 mg • Dihydrocodeine tablets 30 mg • Cyclimorph injection • Diclofenac 75 mg/3 mL Anti-narcotic • Naloxone injection 400 micrograms/mL

5. Central nervous system • Diazepam injection 10 mg/ 2 mL • Diazepam tablets 5 mg • Diazepam rectal tubes 5 mg/ 2.5 mL • Chlorpromazine injection 50 mg/2 mL • Chlorpromazine tablets 25 mg • Haloperidol injection 5 mg/ mL

6. Respiratory system • Aminophylline injection 250 mg/10 mL • Hydrocortisone sodium succinate injection, 100 mg powder for reconstitution • Prednisolone tablets 5 mg • Salbutamol or terbutaline inhaler • Salbutamol for nebulizer • Ipratropium for nebulizer

4. Obstetrics: Syntometrine injection (ergometrine maleate 500 micrograms and oxytocin 5 units/mL). 5. Ophthalmology: Chloramphenicol eye ointment 1%; Fluorescein eye drops 1%. 6. Pediatric: Paracetamol sachets 240 mg; Dioralyte sachets.

2.11

Primary Healthcare Pharmacist

Primary healthcare pharmacists play a significant role in the management of medicines. They have an exceptionally role of deliberate role to focus on maximizing advantage and minimizing risk associated with medicines and planned use of available medicines, inventory management, as well optimizing the use of resources assigned for medicines. In recent years primary healthcare has emerged as a prominent intervention in preventing people from becoming ill. It makes sense to encourage healthier lifestyles as to keep the patient and healthcare admissions to hospital. It would resolve the people getting into a serious health problem and reduce the hospital admissions.

22

A. N. Nagappa and V. Naik

Table 2.2 An overview of the pharmaceutical care process Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9

Establish relationship with the patient: contact and commitment to the patient Collect, synthesize, and interpret the relevant information: Patient, drug, and disease data—Interpret as pharmacist List and rank the patient’s DRPs: Define and prioritize Establish a desired pharmacotherapeutics outcome for each DRP: Quantitative and measurable Determine feasible pharmacotherapeutics alternatives: Desired outcomes Choose the best pharmacotherapeutics solutions and individualize the regimen Design a therapeutic drug monitoring plan: Monitor therapeutic outcome and adverse effect Implement the individualized regimen and monitoring plan: Documentation Follow up to measure success: patient’s basis and long-term basis

Primary healthcare pharmacists work in the local community supporting general physicians, nurses, community pharmacists, and other healthcare professionals. The level of patient contact varies depending on his/her role. Primary healthcare pharmacists play an important role in the management of medicine use and will be involved in developing services for the local population, implementing national health programs such as priorities at a local level, arranging funding and access to health services (commissioning), and designing treatment pathways. Primary healthcare pharmacist will also be involved in conducting health audits and research (Ballantyne 2007). Primary healthcare centers are usually established in rural area and urban area where healthcare facility is difficult to access. They are also providing basic healthcare and management of minor ailments; primary healthcare aims at preventing people from becoming ill and encouraging to adopt healthy lifestyle, as to keep them out of getting admitted to hospital. Primary healthcare pharmacists work in the healthcare centers helping the doctors, nurses, community pharmacist, and other healthcare providers. They play a significant role in maintenance of public health and are responsible for developing services for the local community. They are also engaged in implementing national health programs like eradication of TB, HIV, malaria, and other diseases (Pilnick 1999). They also play a role in arranging funding for access to healthcare services (Table 2.2 and Fig. 2.1).

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

23

Fig. 2.1 Systematic approach for pharmaceutical care

2.12

Pharmacist in Regulatory Affairs

The Department of Pharmaceutical Regulatory affairs is established in government sector and pharmaceutical industries in. The government is responsible for the implementation of its laws and regulations. Pharmaceutical companies must comply with drug rules and regulations. They must submit the documents of good manufacturing practice, clinical trials, and marketing data (pharmacovigilance data). They are also engaged in management of intellectual property rights for the company. The regulatory pharmacists work in an office setting; they have a comprehensive knowledge of drug laws and regulations that are related to manufacturing and procurement of medicines. They may not be in direct contact with patient and health consumer. However, their work and projects will have a direct impact on quality of medicines which in turn influences patients, pharmacist, and other healthcare providers.

24

2.13

A. N. Nagappa and V. Naik

Veterinary Pharmacist

Veterinary pharmacist provides the service for animals like pets, poultry, and animal husbandry. Veterinary pharmacist specialized in treatment of animal diseases and health. Animals are different from humans in their anatomy and physiology. They also get sick and suffer from diseases. Veterinary pharmacist is engaged in stocking, distributing, and dispensing of veterinary medicines to animal owners. They work with veterinary doctors and provide with knowledge regarding the availability of medicines and vaccines (Ceresia et al. 2009). Veterinary pharmacist may be developing expertise in the treatment of pets and large group of animals in dairy and meat industries. Veterinary pharmacist shall be trained in calculation of doses of drugs, routes of administrations, and other aspects of treatment of the animal health. The animals range from small birds to elephants; hence, clear understanding on dose requirements mandates the dose calculations based on principles of animal pharmacology (Lust 2003).

2.14

Conclusions

Pharmacy profession is engaged in multiple services which need a background of pharmacy, therapeutic, and social sciences. The branches of pharmacy are due to services required by the patient. The ultimate objective is to provide the best services which meet the demands of the patient in terms of relief from sufferings and protect the patients from ill effects of drugs without causing much financial burden to the patient.

References Anderson SV, Schumock GT (2009) Evaluation and justification of clinical pharmacy services. Expert Rev Pharmacoecon Outcomes Res 9:539–545 Ballantyne PJ (2007) The role of pharmacists in primary care. BMJ 334(7603):1066–1067. https:// doi.org/10.1136/bmj.39213.660394.80 Ceresia ML, Fasser CE, Rush JE, Scheife RT, Orcutt CJ, Michalski DL, Mazan MR, Dorsey MT, Bernardi SP (2009) The role and education of the veterinary pharmacist. Am J Pharm Educ 73(1):16. https://doi.org/10.5688/aj730116 Deshpande PR, Vantipalli R, Chaitanya Lakshmi CH, Rao EJ, Regmi B, Ahad A, Nirojini PS (2015) Clinical pharmacists: the major support to Indian healthcare system in near future. J Pharm Bioallied Sci 7(3):161–174. https://doi.org/10.4103/0975-7406.160005 Dolovich L, Austin Z, Waite N, Chang F, Farrell B, Grindrod K, Houle S, McCarthy L, MacCallum L, Sproule B (2018) Pharmacy in the 21st century: enhancing the impact of the profession of pharmacy on people's lives in the context of health care trends, evidence and policies. Canadian Pharm J 152(1):45–53. https://doi.org/10.1177/1715163518815717 Draugalis JR, DiPiro JT, Zeolla MM, Schwinghammer TL (2006) A career in academic pharmacy: opportunities, challenges, and rewards. Am J Pharm Educ 70(1):17. https://doi.org/10.5688/ aj700117

2

Pharmacy Profession: Role and Responsibility of Pharmacist in Healthcare. . .

25

Garcia C, Moreda Bermudez I, Gaya Fernandez L (1951) Conception actuelle du rôle du pharmacien militaire en temps de guerre [present concept of the role of a military pharmacist in time of war]. La Presse Medicale 59(53):1099 Harm D (2008) Ministry of Health and Family Welfare (Pharmacy Council of India). Regulations. The gazette of India, New Delhi, no. 19, Part III, Sec 4 , pp 1–97 [last cited on 27 May 2013] Hattingh HL, King MA, Smith NA (2009) An evaluation of the integration of standards and guidelines in community pharmacy practices. Pharm World Sci 31:542–549 Hepler CD, Strand LM (1990) Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm 47:533–543 Kehrer JP, Eberhart G, Wing M, Horon K (2013) Pharmacy's role in a modern health continuum. Canadian Pharm J 146(6):321–324. https://doi.org/10.1177/1715163513506370 Lust E (2003) Educational outcomes in vet 101; a continuing education course for practicing pharmacists in veterinary therapeutics. Pharm Educ 3:237–247 Nichols J, England R, Holliday S, Newton JL (2019) Clinical care pharmacists in urgent Care in North East England: a qualitative study of experiences after implementation. Pharmacy 7(3): 114. https://doi.org/10.3390/pharmacy7030114 Pilnick A (1999) “Patient counseling” by pharmacists: advice, information, or instruction. Sociol Q 40:613–622 Ryan K, Patel N, Lau WM, Abu-Elmagd H, Stretch G, Pinney H (2018) Pharmacists in general practice: a qualitative interview case study of stakeholders' experiences in a West London GP federation. BMC Health Serv Res 18(1):234. https://doi.org/10.1186/s12913-018-3056-3 Simpson SH (2017) The roles we have as hospital pharmacists. Can J Hosp Pharm 70(1):3–4. https://doi.org/10.4212/cjhp.v70i1.1620 Stone L (1998) Good pharmacy practice in developing countries: recommendations for step-wise implementation. FIP Congress Report, Hague Toklu HZ, Hussain A (2013) The changing face of pharmacy practice and the need for a new model of pharmacy education. J Young Pharm 5(2):38–40. https://doi.org/10.1016/j.jyp.2012.09.001 Tumkur A, Muragundi P, Shetty R, Naik A (2012) Pharmaceutical care: need of the hour in India. J Young Pharm 4(4):282–286. https://doi.org/10.4103/0975-1483.104374 Wong I, Campion P, Coulton S, Cross B, Edmondson H, Farrin A, Hill G, Hilton A, Philips Z, Richmond S, Russell I (2004) Pharmaceutical care for elderly patients shared between community pharmacists and general practitioners: a randomised evaluation. RESPECT (randomised evaluation of shared prescribing for elderly people in the community over time) [ISRCTN16932128]. BMC Health Serv Res 4(1):11. https://doi.org/10.1186/1472-6963-4-11

3

Pharmacist: Background, Knowledge, and Skills A. N. Nagappa and Vaishnavi Naik

Abstract

Pharmaceutical science is a blend of engineering and health sciences. Pharmaceutics is the science and art of converting crude drugs into formulations which can be given to the patients. The industrial practices are an integral component of pharmacy as the manufacturing of medicine to cater the treatment of a large number of people. After manufacturing the medicine, it needs to be dispensed to patients who do not have knowledge or experience about medicines. Hence, every patient needs to be briefed about how to store, use, and avoid side effects of the drugs. Keywords

Communication skills · Clinical skills · Business acumen · Drug information skills · Detailing skills

3.1

Pharmacist Background

Evolution of pharmacy profession has as an interesting anecdote. In times immemorial, before the dawn of civilization, humans lived in caves, and cavemen observed the nature and developed knowledge to use available resource in curing diseases and suffering. Healthcare provision was a welfare activity, and a person engaged in providing healthcare was called as Apothecary/Vaidya. The Apothecary and Vaidya

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_3

27

28

A. N. Nagappa and V. Naik

are regarded as Gods, as they were helping the diseased and making them to get back into health. The saying about Apothecary/Vaidya as “Vaidya Narayana Hari” is not a mere expression but a deep-rooted respect for healthcare professionals, which we observe even today. The healthcare provider was respected as God who provided services without expecting any money or favors from the patients. The kings and emperors used to provide patronage to Apothecary/Vaidya’s who were looked upon them and one of the successful Apothecary/Vaidya were appointed as Chief Apothecary or Raj Vaidya whose responsibility was to provide healthcare to the state and royal families (Alhomoud 2020). The Apothecary/Vaidya used to wander forests in search of medicines, as it was the only source for crude drugs and material of medicines, as cosmical based industries were not available. Apothecary/Vaidya became experts in identifications of medicinal plants and herbs. They collected and used them in preparations of formulations. They also developed a skill about how to use the collected medicine among patients. They prepared extracts of crude drugs with available solvents like water, honey, and juices of fruits. They did lots of empirical efforts to treat patients and help them get freedom from diseases. Apothecary/Vaidya acted as a one-man army, who did the entire work of healthcare provision from collection of medicine to administering drugs to patients which includes A to Z things of a patient pharmaceutical care. In due course of time due to accumulation of a large amount of medical knowledge and increased patient numbers, the Apothecary/Vaidya occupations become huge and become difficult to do justice to patients. At this juncture, Apothecary/Vaidya decided to divide their work and redistribute so that the treatment of patients becomes handy and feasible (Sam and Parasuraman 2015). Apothecary/Vaidya split their work into three major divisions and initiated institutional practice of healthcare delivery. The division of labor among them leads to the profession of doctor, nurse, and pharmacist. All the demarked roles of healthcare providers into doctors, pharmacists, and nurses are extensible when a professional is not available. Each healthcare provider should have the basic skills to handle other healthcare professional role in times of necessity and emergency. The pharmacist was given the role of managing all the aspects of medicine. They are responsible for drug discovery, drug development, manufacturing of formulations, distribution of medicines, and dispensing of medicines. Pharmacists are also supposed to provide pharmaceutical care to the patients. The pharmacist provides the care in collaboration and direction of a doctor/nurse, who is specialized in finding out and pinpointing the nature of the disease (diagnosis) and patient care. The prescription is an important professional document connecting all the healthcare providers. The prescription should be handled carefully as any discrepancy or error can cause patient harm and failure of therapy. Some patients who are seriously ill need to be treated in Hospitals and nurses should. Nurses who are providing healthcare service are engaged in drug administration. The pharmacist should work in close association with nurses for ensuring proper dose, ADR monitoring, and patient safety by giving proper inputs to nurses and help them in providing comfort and care to the patients (Habeeb et al. 2012).

3

Pharmacist: Background, Knowledge, and Skills

29

Over the period, all the three core healthcare professionals have developed and emerged as pillars of modern healthcare practices. The healthcare professionals have their own professional logos, identity, organizations, councils, and ethics of professional practice. The councils are established by professional acts enacted by respective governments which guide and regulate the correct professional conduct and practice. They are responsible for functioning of registered members and provision of professional services. Councils are supposed to monitor professional conduct of their members. It is very much necessary to establish a system of healthcare provider an environment for conflict less practice of each profession. The individual professionals who belong to particular professional councils must be managed by their own councils which has membership of practicing professionals, for example, the Medical Council of India, Pharmacy Council of India, and Indian Nursing Council. These councils are established by the Act of Parliament. For example, the Pharmacy Council of India is established by provisions of Pharmacy Act 1948. In India before 1948, there was no restriction for practice of pharmacy profession. Quacks and nonprofessionals were practicing who had no knowledge about drugs. The establishment of council has put to an end to the practice of profession by quacks and unauthorized persons. The provision for establishing standard professional education system was possible by enacting education regulations. The anarchy in healthcare system was put to an end by enacting and enforcing the healthcare councils (Deshpande et al. 2015). The salient features of Pharmacy profession Act 1948 provide an establishment of central and state Pharmacy Council of India, pharmacy education regulations, and registration of pharmacist; the law clearly restricts nonpharmacist and restricts practice of profession to pharmacist.

3.2

Pharmacist: Knowledge

Pharmacist always worked in the background and remained obscure in the public preview as for the profession in the society. However, the community pharmacy has become the public face of pharmacy profession due to their constant interaction with the patients and health consumers. Pharmacist by training has an extensive knowledge of medicines beginning from basic research to patient care, which is known as bench to bedside. They are experts having skills of drug formulations, where they convert the basic crude drug into practically unstable medicine. The formulations of tablets, liquid orals, capsules, ointments, injectables, suppositories, pessaries, eye drops, eardrops, and nasal drops are made by pharmacists. Special products include aerosols, inhalers, and metered dosage forms. The special products like targeted drug delivery systems and sustainedrelease products are also made by pharmacists. Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in such a way that it includes a dosage form. Formulation studies involve developing a preparation of the drug

30

A. N. Nagappa and V. Naik

which is both stable and acceptable to the patient. For orally taken drugs, this usually involves incorporating the drug into a tablet or a capsule. The manufacturing activity is carried out in a large scale for meeting the demand of the patients. They also watch the medicines manufactured do not cause harm to the patients while using them. They also take care that the medicines produce good effect in patients and improve the quality of life. Their extended responsibility includes making the drugs affordable to a large number of people. Pharmacist should also practice pharmaceutical care, pharmacoeconomic, pharmacovigilance, and outcome research (Waterfield 2010). The pharmacist is known to do multitask practices which make them to study basic health sciences and core pharmaceutical faculties, viz., pharmaceutical chemistry, pharmacognosy, pharmaceutics, and pharmacology. The professional practice of pharmacy needs knowledge of biotechnology, communication, social behavioral science, pharmaceutical analysis and regulations, and computer science. Basic health science includes human anatomy and physiology, biochemistry, microbiology, and pathophysiology (Droege and Baldwin 2005). The pre-pharmacy registrations require basic knowledge in physics, chemistry, biology, and mathematics, the core pharmaceutical subjects. Pharmaceutical chemistry includes medicinal chemistry of drugs, synthesis, and physicochemical chemical aspect of drugs; further pharmaceutical chemistry includes computer-assisted drug design. Pharmacognosy is the study of natural drugs including medicinal plants, drugs from animal origin, and microbiological drugs. Pharmaceutics is the science and art of making medicine formulation by using basic drugs and other excipients, for example, in making 100 mg of drugs in tablet formulation, we need excipients like binding agent, disintegrating agent, and diluents along with active pharmaceutical ingredient. They may also need colors, flavors, and sweetness to improve organoleptic properties of the formulations; for making the powder into tablet, we need glidants. Sorbents are used to protect tablets from moisture and keep the product in dry state. Pharmacology involves the study of interactions that occur between a living organism and medicines that affect normal and abnormal biochemical functions. Pharmacology studies include theoretic application of drugs and adverse drug reactions including side effects (Nowotny et al. 2001). Biotechnology contribution to therapeutics is immensely very important, for example, human proteins by cDNA technologies yielded molecules like human insulin interferon and erythropoietin for therapeutic applications. Hybridoma technology led to the supply of monoclonal antibodies like rituximab which are used in diagnostic test, to purify antibodies. Therapeutic effectiveness of monoclonal antibodies in cancer treatment, for example, alemtuzumab, bevacizumab, cetuximab, gemtuzumab, ipilimumab, panitumumab, pembrolizumab, ranibizumab, rituximab, and trastuzumab. Further biotechnology is also offering cure to many diseases by gene therapy. Biotechnology is an important tool which is changing the treatment of diseases. Communication is fundamental for providing patient counseling, drug information services, patient education, and discharge medication counseling. This skilloriented topic must be perfected by case studies and active training to the young

3

Pharmacist: Background, Knowledge, and Skills

31

pharmacist. The communication should be effective so that the service receiver should not have any problem in following the instructions given by the pharmacist. Social behavioral science is about how to interact with patient and health consumer to communicate the exclusive information in a candid manner. Patient and health consumer approach the pharmacist in a confidential manner regarding their drugs, diseases, and lifestyle. The pharmacist enjoying the trust of patient and healthcare shall provide with explicit information ensuring privacy. Here the community pharmacist faces a challenging situation in protecting patient confidential information. Patients also have a lot of misbelieves and myths regarding diseases, drugs prescribed, and lifestyles. The patients are having apprehension regarding drugs and diseases and are under stress. Pharmacist should counsel the patient. If not properly counseled, the patients out of ignorance may stop medication. It usually happens so the symptoms of disease are likely to stop much before the cure. This gives an impression that the disease is cured and may stop using the medicine before the prescribed course of treatment. For example, in treatment of tuberculosis and typhoid due to discontinuing of the treatment in the mid of the course, there is a relapse of infection with resistant strains of bacteria (Traulsen and Bissell 2004). Pharmaceutical analysis is a branch in pharmacy which is responsible for identification and confirmation to purity and assay for content of active pharmaceutical ingredients as per the standards mentioned in monograph of pharmacopeia. The quality control and quality assurance are important responsibilities utilizing pharmaceutical analysis. By practice of pharmaceutical analysis, one can provide high quality of medicines; hence, it is a mandatory work of pharmaceutical industry. Pharmacists are supposed to handle sophisticated instruments like UV, Visible, IR, Mass, NMR, Spectrophotometers for quality control and quality assurance. There are various regulations which govern the pharmacy profession and professional practice. The knowledge about the law is essential for practice of profession and conduct of business of pharmacy. As such most of the drugs which are having potential to harm the public health are regulated by Drugs and Cosmetics Act, 1940. It regulates the import, manufacture, distribution, and sale of drugs and cosmetics. It also mandates that all drugs and cosmetics imported into India shall comply with the prescribed conditions. Even the standards about labels, storage conditions, and maintenance of documents are to be stringently followed. The manufacturing facilities are subject to inspection by regulatory agencies, who are supposed to ensure that the manufacturing of drugs and manufactured products is as per the standards of government. Manufacturers of all class of drugs require prior license which should be acquired to the manufacturer following an inspection. The Pharmacy Act 1948 regulates Pharmacy Profession Education and Pharmacy practice. Drugs and Magic remedies Act, 1954, governs the advertisement regarding medicines in the mass media. Alcohol has usages in manufacture of medicine, cosmetics, and alcoholic beverages. For government, alcohol aids as revenue generating source and collecting taxes. Alcohol is essential for making some medicines and cosmetics. The taxes for alcohol for manufacture of medicines are essential, and a low rate of tax is levied.

32

A. N. Nagappa and V. Naik

Alcohol used for manufacture of cosmetics is levied higher rate of taxes as it is considered as luxury. Alcoholic beverages are charged with highest possible taxes as it is consumed for entertainment and pleasure. Medicinal and Toilet Preparations (Excise Duties) Act, 1955, divides alcoholic preparations into three categories. The first one is alcohol in medicines, second one is alcohol in cosmetics, and third one is alcohol for drinking purpose. Drugs like morphine, heroin, cocaine, and cannabis are used as psychotropic substances. The drugs are habit forming and are detrimental to family and community. There is a need for controlling these drugs strictly as criminals can establish syndicate and exploit the innocent people by indulging in supply of drugs. Narcotic Drugs and Psychotropic Substances Act, 1985, prohibits a person to produce, manufacture, cultivate, possess, sell, purchase, transport, store, and consume any narcotic drug or psychotropic substance. However, pharmaceutical industry uses these substances for making medicine. This law is essential for pharmaceutical industries on how to manufacture and sell narcotic and psychotropic drug substances in the market. Computer sciences and computers have revolutionized all aspect of life. Applications of computers are innumerable and important to pharmacy. It is used in drug manufacture, distributions, dispensing, and pharmacy practice. It is very important to know smartphone applications in healthcare delivery and disease management. Basic health sciences are foundations for development of core pharmacy knowledge and skills. The human anatomy and physiology, biochemistry, pharmaceutical engineering, physics, chemistry, mathematics, and biology are essential to understand core pharmaceutical faculties. Pathophysiology, microbiology, and biostatistics are core supporting allied biological sciences of pharmacy profession.

3.3

Pharmacist: Skills

Skill is an ability to do something well and smart. The skills can be often divided into generic and specific. Skill is an ability and capacity acquired through a deliberate, systematic, and sustained effort to smoothly and adaptively carry out complex activities or job functions involving ideas (cognitive skills), things (technical skills), and/or people (interpersonal skills); see also competence. Generic skills for pharmacy include accuracy, integrity, communication skills, advocacy skills, management skills, multitasking skills, diplomacy skills, ability to prioritize, analytical skills, finance skills, and mentoring skills; specific skills include attention to detail while attending a patient, computer literacy, mathematics, science, ability to operate pill-counting machines, and good interpersonal communications. Pharmacy professional practice can further be subdivided into industrial practice research, marketing, and professional practice. The skills required in industrial practice research and marketing are not discussed further as this book. Here we focus on pharmacy practice skills required by professional practices. Pharmacy practice has three main branches, viz., clinical, hospital, and community pharmacy.

3

Pharmacist: Background, Knowledge, and Skills

33

Clinical pharmacy and hospital pharmacy are practiced in corporate hospitals, teaching hospitals, and disease-specific hospitals like hospital for cardiology, mental health, cancer, nephrology, and nursing hospitals. Here patients get admitted for getting treatment for health conditions which are usually critical and bothersome. Community pharmacy operates in the marketplace where a registered pharmacist occupied in dispensing and compounding activities under the prescriptions of registered medical officers. Clinical Pharmacists jobs mainly involves engagement with patients, and they are responsible for physical assessment along with counseling responsibilities, are engaged in soap analysis (subjective, objective, assessment, and treatment), and also review the reports of lab and diagnostic test and monitor the drug therapy. The hospital pharmacist is based in hospitals and in nursing homes; hospital pharmacist is expected to advise patients and work closely with medical and nursing staff onwards so that most appropriate treatment is being delivered. The Roles and responsibilities hospital pharmacist and clinical pharmacist usually overlap, and they differ in work portfolio, for example, hospital pharmacist is engaged in manufacture of medicines for the prescription of the hospitals; hence, skills for clinical pharmacy and hospital pharmacy are discussed together, and a separate discussion is included where the role is different (McDonough and Bennett 2006; Meldrum 1994).

3.4

Skills for Clinical and Hospital Pharmacists

Pharmaceutical care is the major activity of all the three pharmacists provided to patients and healthcare provider (Fig. 3.1). Pharmaceutical care starts inovles with patient’s assessment including assessment of physical conditions and collection of medication history along with interviewing the patient’s relevant documents. Treatment problems can be monitoring the following standard treatment protocols and evaluations of drug utilization. Pharmaceutical care plan should be customized to the patient’s specific conditions and needs; it should include the review of untreated conditions, address drug reactions and drug interactions, and optimize dose requirement; they should also be able to assist the healthcare team in optimizing individual dose by the knowledge of pharmacokinetics. Clinical and hospital pharmacists should also be well equipped with patients and counseling skills; they should also monitor discharged patients and focus on providing information on drugs, diseases, and lifestyle modifications which improves the quality of life. They are supposed to provide discharged medication counseling for all the patients who get well and go home and continue the prescribed medications (Barnette et al. 1996). The clinical pharmacist is mainly engaged in the ward rounds and assists doctors and nurses in responding drug information queries and patient-specific drug treatment protocols along with dose adjustment (Fig. 3.2). Hospital pharmacist is engaged in making medicines as per the prescriptions and also involved in manufacture of IV fluids and other formulations required to be used in the hospitals (Fig. 3.3).

34

A. N. Nagappa and V. Naik

Fig. 3.1 Clinical pharmacy requirements

Community pharmacist enjoys special respect and status by the patient and health consumers due to their easy accessibility. Patient and health consumers consult them for many health issues and conditions. Community pharmacists are known to increase trust and commitment of the patient and health consumer. They are pursued for advice in the matter of nutraceuticals and healthy foods along with wellness products. Pharmacist shall engage in overseeing the problems and issues in prescription while dispensing. He/she also prepares the pharmaceutical care plan by which he/she engages in monitoring the disease condition. He/she is responsible for protecting his clients from drug-induced injuries while using the prescribed medicines.

3.5

The E-Prescription and Electronic Health Records

The current role of pharmacist is getting metamorphized due to advances in technology, patient demand for services like E-prescriptions, electronic health records, home medication review, health management organization, and drug information services. In E-prescriptions, the prescriptions are written by the doctors in a computer form and electronically transferred to pharmacy. The pharmacist fills the prescription and waits for the patient to collect the medicine from the pharmacy. In conventional system Pharmacist, the patients were handed over the paper prescription which he checks manually and prepares and dispenses the medications, manually checks prescription, and prepares the basket of prescribed medicine. The

3

Pharmacist: Background, Knowledge, and Skills

Fig. 3.2 Role and responsibility of clinical pharmacist

Fig. 3.3 Function of hospital pharmacy

35

36

A. N. Nagappa and V. Naik

patient is attended by a pharmacist and counseling of important points is given. In electronic prescriptions the prescription errors have come down and improved ease of business. The electronic health record is the service provided by the pharmacy on demand by the patients. The electronic health record is an electronic form in which patient profiles are made and are available on request by the patient/doctor. It has provision to enter all the relevant information of the patient like patient demographic detail, blood group, medication history, drug allergies, lab reports, current diseases, and current medications. This profile helps one to provide pharmaceutical care and saves time when patient is referred for treatment in a hospital (Porterfield et al. 2014). Home medication review is a service for the outpatients and patients who request the service to be provided at their own residence, for example, dialysis for renalimpaired patients. In home medication review model, pharmacist visits the patient at home by appointment and checks the patient’s blood pressure, blood sugar, and some other tests. He/she may also provide injection services and vaccinations. In home medication review, pharmacist verifies the medication used by the patient and assesses the health outcomes due to treatment. He corrects the mistakes the patient may be doing while taking medicines. Health management organization is a team of healthcare professionals who aim at providing consultancy to patients or patient organization in terms of health. A Pharmacist is a core member of the health management team and attends the aspects of drugs and other related aspects of health, for example, smoking cessation, contraceptive counseling, and obesity management. Drug information services are provided in setups of clinics, hospitals, and stand-alone community-based kiosks. Here the healthcare provider or patient utilizes the services regarding specific information about drugs they are using. Drug information centers have paid online subscriptions like Micro Medics, Lexicomp, and Medscape. The drug information specialist who is a pharmacist has special skills to discuss the issue with the client and go through the databases and make customized information file and deliver it to the client (Samadbeik et al. 2017; Kohn 2011). • Communication: Pharmacists need to communicate with doctors when questions arise about prescriptions, and they need to communicate with patients who have questions about what has been prescribed, potential side effects, and more. • Analytical skills: The pharmacist has to evaluate patient’s needs and the prescriptions of doctors to be sure proper medications are being given in the proper doses and appropriate combinations. • Detail-oriented: Prescriptions must be accurate and appropriate for patients. Errors can have serious consequences for the health of patients, so it is vital that pharmacists be precise about every prescription they fill. • Business acumen: Pharmacists who run their own businesses need to have the skills to oversee a retail establishment, including hiring staff, maintaining a budget, and more. This job generally requires the ability to do the following work:

3

Pharmacist: Background, Knowledge, and Skills

• • • • • • •

Fill prescriptions. Instruct and advise patients. Administer vaccinations. Consult with doctors. Work with insurance companies. Maintain records. Manage a retail business.

3.6

37

Conclusion

The students are trained to handle the situation in pharmacy which requires multidiverse skills like dispensing skills, compounding skills, counseling skills, business documentation skills, first aid, and clinical skills. The patient expects quick response and services and has little patience. The pharmacist should engage in continuation of education by attending professional development program and adoption of skills, and practice is important.

References Alhomoud FK (2020) Pharmacists’ background, interests, barriers, self-perceived competence and confidence to design and undertake pharmacy practice-based research in the GCC geographic area. BMC Med Educ 20:411. https://doi.org/10.1186/s12909-020-02346-4 Barnette DJ, Murphy CM, Carter BL (1996) Clinical skill development for community pharmacists: community practitioners work with colleges of pharmacy to better train pharmacists to provide patient-focused care. J Am Pharm Assoc 36(9):573–581 Deshpande PR, Vantipalli R, Chaitanya Lakshmi CH, Rao EJ, Regmi B, Ahad A, Nirojini PS (2015) Clinical pharmacists: the major support to Indian healthcare system in near future. J Pharm Bioallied Sci 7(3):161–174. https://doi.org/10.4103/0975-7406.160005 Droege M, Baldwin HJ (2005) Have things changed in pharmacy education? J Pharm Teach 12(1): 5–9 Habeeb IAR, Jose D, Jegan RS (2012) Pharmacists in the wider public health workforce – a review. Arch Pharm Pract 3(2):166–169 Kohn LT (2011) Electronic prescribing: CMS should address inconsistencies in its two incentive programs that encourage the use of healthy information technology. DIANE Publishing, Washington, DC McDonough RP, Bennett MS (2006) Improving communication skills of pharmacy students through effective precepting. Am J Pharm Educ 70(3):58. https://doi.org/10.5688/aj700358 Meldrum H (1994) Interpersonal communication in pharmaceutical care. In: Essential Interpersonal skills for pharmacy practice: communication in counseling and conflict contexts. Pharmaceutical Products Press, Binghamton Nowotny H, Scott P, Gibbons M (2001) Re-thinking science: knowledge and the public in an age of uncertainty. Polity (Blackwell), Cambridge Porterfield A, Engelbert K, Coustasse A (2014) Electronic prescribing: improving the efficiency and accuracy of prescribing in the ambulatory care setting. Perspect Health Inf Manag 11:1g

38

A. N. Nagappa and V. Naik

Sam AT, Parasuraman S (2015) The nine-star pharmacist: an overview. J Young Pharm 7(4): 281–284 Samadbeik M, Ahmadi M, Sadoughi F, Garavand A (2017) A comparative review of electronic prescription systems: lessons learned from developed countries. J Res Pharm Pract 6(1):3–11. https://doi.org/10.4103/2279-042X.200993 Traulsen JM, Bissell P (2004) Theories of professions and the pharmacist. Int J Pharm Pract 12(2): 107–114 Waterfield J (2010) Is pharmacy a knowledge-based profession? Am J Pharm Educ 74(3):50. https://doi.org/10.5688/aj740350

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on Outcomes, Quality of Life, and Cost of Treatments A. N. Nagappa and Vaishnavi Naik

Abstract

The patients are totally ignorant as for the disease drugs and usage of medicine prescribed to them by their doctors. The medicines are chemical entities which are capable of interacting with human body. The patients usually take it for granted that medicines are developed from a scientific background and are safe for use without many conditions. In case medicine is to be taken for a long time like in chronic conditions, then medicines are likely to cause serious side effects. It is very important for a pharmacist to identify and resolve the problem before the event becomes a casualty and causes a drug-induced safety issue for the patient. Practice of pharmacy practice skills will prevent the ill effects of the drugs. Keywords

Medication error · Look-alike and sound-alike · Dispensing errors · Quality of errors · Cost of medication error · System error and drug administration error

4.1

Gaps in Knowledge

In healthcare practice, if there is careless approach in terms of treatment, it can lead to disastrous accident leading to major harm or death of patients. Such circumstances are more common in developing countries where accountability and documentation of service provided are lacking. In a hope to improve the quality of treatment and life

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_4

39

40

A. N. Nagappa and V. Naik

of patients, updating the knowledge is very much essential. Practically replacing the old knowledge in practice seems to be very much difficult. The healthcare providers are comfortable with their existing knowledge and are confident in providing treatment due to no accountability or documentation of treatments. Researchers are finding and adding new knowledge in a hope to improve healthcare system. It is always desirable to apply latest knowledge for treatment of patients instead of the present knowledge. In this process, there is a delay in adopting new approach, drugs, and treatment. However, it is observed that many healthcare providers although aware of shortcoming of the current therapy would not like to change to new therapies. For example, beta-blocker propranolol was introduced as antihypertensive agent. It was soon realized that propranolol is a nonspecific beta-blocker. Due to its nonspecific blockade of beta receptors, it was causing exacerbation of asthma in hypertensive patients. To overcome the exacerbations of asthma, atenolol specific beta 1 blocker was introduced in therapeutics. Atenolol does not cause exacerbations of asthma and produces antihypertensive effect. The changeover from propranolol to atenolol took considerable amount of time in order to convince doctors and was adopted into practice of medicine. However, in many circumstances, clear-cut advantage like in the above case may not be available. The pharmacist should do an extensive literature review and prepare a convincing summary and present it to doctors and nurses to change their concepts. For doing literature review, there are resources like randomized controlled trials, systematic review, and meta-analysis available. There are many online dedicated databases which are engaged in continuously updating classified information. This information can be accessed and made available by Micromedex, Lexicomp, and Medscape. It is the clinical pharmacist who can be able to provide the doctors and nurses the information in a customized manner. The clinical pharmacist who is engaged in providing drug information to healthcare providers and patients is called drug information specialist. Drug information specialist can look in for classified drug information and prepare a summary or note, so that healthcare professional can use the latest information. Due to cultural limitations, it is difficult to change the existing system of practices. Despite availability of latest information, it is hardly utilized due to various issues and problems. For example, the serious ADR of proton pump inhibitors like omeprazole having an ADR leading to anemia is prescribed rampantly. Osteoporosis and supra-infection by Clostridium difficile are the major side effects of proton pump inhibitors that are not emphasized as this would result in less prescriptions and sale of the proton pump inhibitors. The drug information is not practiced in clinical setups seriously, but the drug information provided by the pharmaceutical industries as a marketing effort is accepted by the clinician. The conventional approaches of changes happen by detailing, endorsement’s key opinion leaders and peer referrals. This approach results in biased information that becomes a basis of therapy in many instances. The drugs are being known for its variety of interactions with the human system. It is very important to use restraint while using prescription medicines. One should be alert while writing a prescription of medicine and should be based on risk-benefit

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

41

ratio of outcome. Before writing a prescription, practically it may not be possible to predict risk-benefit ratio beforehand; however rough estimate and speculation of ADR are always possible for a prescriber. It is only possible to enforce if there are documentations and accountability for prescription of a medicine. The medicines are usually administered to the whole of the body although they are required to act on a particular target. It so happens that most of the drugs are subjected to the process of absorption, distribution, metabolism, and excretion (ADME) when given by oral route. It is noted here that in polypharmacy, a greater number of drugs are administered for multiple conditions. When the drugs are administered together, there can be a possibility of drug-drug interaction. The pharmacist should be alert to avoid any such drug-drug interactions which are going to produce serious health issues and causality. The evidence-based medicine (EBM) is one of the recent approaches to modernize the medical practice. In EBM, evidence is presented in a candid manner by which practitioner understands the available evidence so that rational decision in the interest of patients can be taken. The primary source of evidence-based practice is to collect relevant information from published literature which is organized and presented to the doctors and patients. Evidence which is collected by case reports and by key opinion leaders is considered the weakest source of information. Further information from animals in vitro/in vivo studies are from the published review for the clinical information is also not appropriate. Information from cross-sectional studies, case control studies, and cohort although relevant but crude. The best possible evidence comes from randomized clinical trials which are considered as a gold standard for evidence-based practice. The synthesized/derived information from meta-analysis and systematic review are the strongest evidence for practice of evidence-based medicine. The meta-analysis combines prevailing evidence from relevant randomized controlled trial and synthesizes new evidence, while systematic review gives comparative evidences and summary of evidence in a one look by representation as forest plot. Graphically on forest plot, one can quickly understand the status information from prevailing RCT. This helps the clinician to make an informed decision. This is acceptable as it is the summary of several studies on a single clinical question for which the answer is being sought. Recently new development in meta-analysis is available as network meta-analysis. In network metaanalysis, real-time data is also included in synthesis of evidence of medical knowledge.

4.2

Patients and Healthcare Consumers (P&HC)

Patient and healthcare consumers are very much interested in drug information, especially for those medicines, when they are prescribed for them. Patient and healthcare consumers for their need of information visit internet search engines. The most popular sources of information are Google and Yahoo to learn about medicine they are using. Information on the Internet is popular because it is free, easy to access, and easy to understand, with ensured privacy. Major drawback is that

42

A. N. Nagappa and V. Naik

it is passive, not authenticated or evaluated, and misleading as advertorial. However, there are agencies like health on NET, Solberg scores, Hogner Sandvik scale, Jim Kaprun’s, and the Health Information Technology Institute (HITI) criteria which assess and certify the websites for the authenticity of health information posted on the website. Other sources of drug information for patient and health consumers include mass media such as newspapers and inserts in daily newspapers which are product promotional materials rather than an unbiased drug information. There are also paid news-cum-editorials which clandestinely promote the use of the medicines in newspapers. The government in order to control and prevent media from publishing the wrong information about drugs for business and promotion purposes has framed the Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954. Drugs and Magic Remedies 1954 is an Act of the Parliament of India to control the advertising and unnecessary wrong publication of drugs in India. It prohibits advertisements of drugs and remedies that claim to have magical properties. However, this stand-alone act without implementing agency has remained unproductive in controlling of advertisements regarding medicines. The newspapers and televisions are full scale in the roads for advertisements of medicines in full public preview, violating the Act in upfront. The information in the advertisements is highlighting the importance of medicine in giving quick relief and promoting its use; the advertisement hides the side effects and other risks involved while using the medicines. The public are under the myth that medicines can hardly damage their health as they are scientifically evaluated for safe to consume. Patient and healthcare consumers who are under the influence of advertisements begin self-medicating themselves with false faith of safety, which is very dangerous. In a classic but tragic reported case of abusing steroid topical by a woman as beautifying aid for several years started showing up the classical ADR of steroids. She developed moon face and deposition of fat in the abdomen skin, with thin and fragile bones. Her immune system gets superseded as she would catch up with frequent infections of bacteria and fungus due to compromised immunity; soon she developed diabetic with cataract in both eyes. There are many drugs like topical steroids wherein patient and healthcare consumers engage with self-medication without their knowledge and become victim of self-medication and experience unwanted side effects (Table 4.1).

4.3

Medication Abuse

Prescription medicine abuse has become a fashion in modern society. We find increasingly complex health issues leading to harm to the patients which are preventable. It has become very important to find and put in practice the ways we use medicine and improve the safety. It becomes very important to understand the dimension of medication abuse. The use of medicine by the patient can be transformed to abuse without the notice of the patient himself. In some instances, the patient unknowingly gets into the habit of taking medicine after prolonged use of

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

43

Table 4.1 Commonly abused OTC drugs as self-medication by patients and health consumers S. no. 1 2 3 4

Medicine Dextromethorphan (DSM) Cold medicines Ibuprofen Milk of magnesium

Categories Cough medicines Pseudoephedrine Pain relievers Laxatives

Abuse Recreation

Effects Nervousness and restless

Steroids

Recreation Overdose Weight lose Weight lose Beautify

Loperamide

Antidiarrheal

Habitual

8

Diazepam

Sedative

Recreation

9 10

Alcohol Dimenhydrinate

Recreation Recreation

11

Acetaminophen

Depressant Motion sickness pills Pain relievers

Nervousness and restless Kidney and liver problems Electrolyte and mineral imbalances Electrolyte and mineral imbalances Rapid weight gain and unusual mood swings Abdominal pain, constipation Changes in appetite, difficulty keeping balance Liver and nervous damage Drowsiness or dizziness

5

Furosemide

Diuretics

6

Betamethasone

7

12

Pantoprazole

Antihyperacidity

Habitual

Habitual

Nausea, vomiting, loss of appetite, or severe stomach pain Weight changes, nausea, vomiting

medicine, for example, Otrivin nasal drops. This is the basis of medication abuse, and correcting and getting rid of medication abuse need nonmedical intervention and counseling, e.g., tobacco addiction (McLellan 2017).

4.4

Medication Error (ME)

Medication errors are broadly defined as any error while prescribing, dispensing, and administrating of a drug, irrespective of adverse effect and side effect consequences of drug. The medication errors are preventable causes leading to patient safety and efficacy issues of morbidity and mortality. The drugs are prescribed by a doctor, dispensed by a pharmacist, and administered by a nurse. In this process, there can be a communication gap leading to medication error. The safe approach of medication use is the collective responsibility of healthcare providers (doctors, nurse, and pharmacist) along with patients. The doctors who prescribe medicines should always be in communication with nurse and pharmacist and refer them to identify and inform any safety issues foreseen by them. The use of generic names in prescription would eliminate the prescribing errors; the customization of prescribing individual patient can minimize the errors in prescribing. Thorough medication history is essential to prevent any hazardous event. Prescribers should also identify high-risk medicines and take appropriate precaution while prescribing them. The prescriber

44

A. N. Nagappa and V. Naik

should also be familiar with the medicines he is prescribing. The healthcare team should alert the patients to provide feedbacks on strange experiences while on medication. One should continuously learn and remember the medication errors happened by documenting the events. The side effect is drug reaction if a drug causes other effect than the primarily intended effect. It is easy to predict a side effect of a drug. Pharmacist can alert about the possible side effect while dispensing the medicine. This would cause a panic in patient, if he is not aware regarding the side effect of the drug. He may end up with a casualty, if the patient is unaware about the side effect of the drug, causing sleep engages in driving or any other activities demanding alertness (Patel et al. 2016). It is the duty of pharmacist to inform the patient about side effects of the drug while dispensing such medicine. For example, opioid analgesic often causes nausea. The adverse reactions are those events which are unpredicted causing a harm to the patients, for example, allergic reaction in a patient for the first time while using the medicines like vaccines. Failure to carry out a planned action or using an incorrect handling may lead to serious consequences for the patient. Adverse drug reaction is an error, while adverse event is an incident which results in harm to a patient. An adverse event may be preventable or may not be preventable. In an ADR, a patient may be harmed or nearly harmed or may not be harmed, or it may also fatal. In case of serious adverse drug reaction, there should be preparedness to attend medical emergency. For example, anaphylactic reaction of penicillin injections needs immediate medical help. Medication errors are preventable if identified before drug administrations. The steps involved in medication usage involve prescribing, administering, and monitoring the patient. When choosing an appropriate medicine for a given clinical situation for the patient, one should look into the patient medication history or his electronic health record, even asking the patient whether he is allergic to any medicine in their medication history. This simple step shall avoid a severe ADR. Considering the factors of allergies, one can even give a test dose to check and to confirm allergic manifestation. Subsequently selection of route of administration, dose, time, and regimen are the other factors. Communications and discussions of the treatment plan by the doctors with the nurse/pharmacist and patient are very important. Documentations of the prescribing and treatments are essential for retrieval of the medication plan history (Gaur et al. 2012). Lapses in prescription can happen when prescriber has no clarity about the drug indications and contraindications, overlooking individual patient’s factors like allergies, pregnancy, and comorbidities along with patient using already on other medications. The prescriber is responsible, if the prescription is written by mistake to a wrong patient, dose, time, and drug or wrong route of administrations. Improper communication of written or verbal can lead to prescribing errors. Ambiguous, incomplete, and illegible prescription and documentation is one of the major causes of a medication error. One should also be careful about calculation of doses of medicine and mathematical errors incorrect data entry may lead to duplication or omission or wrong medicine. The branded drugs names may be also be a source of medication error. In India there are nearly 1 lakh registered brands. The registration

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

45

of the brand medicine is done at state drug control departments; each company has made its formulation, given a name of its choice, and developed the brand by name. Finally, when we see the names of the brands available in the country is much confusing due to look alike and sound alike names of the drugs. Drugs with similar names are threat to patient safety; sometimes the prescription may be wrongly interpreted by the pharmacist. For example, sertraline and cetirizine are likely to be interchanged if the prescription is communicated by phone. Even in written prescription, there can be a medication error. It is very important to take care about legibility in prescriptions and also regarding look-alike and sound-alike names of the drugs. The five ‘Rs of the correct prescription are the right drug, right route, right time, right dose, and right patient to minimize medication error. Medication error can also happen in the choice of medicine like underdosing the medication or overdosing of medication, inappropriate drug prescribed, ineffective drug prescribed, and irrational prescribing. Prescription error usually happens due to illegibility in prescription writing. Medication error may also happen during manufacturing in respect to the strength of the medicine or contamination or adulterants due to wrong labeling and packaging. Medication errors are also happening while dispensing a formulation like wrong drug/formulation and label being dispensed. Medication error may occur during drug administration to a patient. Drugs need to be administered as specified. If the patient receives like wrong dose/route of administration/frequency/duration, it can lead to a medication error. While monitoring drug therapy if medication error happens, it is the responsibility of the healthcare provider to manage the patient and take preventive measure to ensure patient safety. Medication errors can occur at different stages of patient care. It may begin at prescription writing where a doctor intentionally uses a coded script. This type of practice was very much prevalent, as many doctors were thinking that if patient get familiar with drugs names, he/she may indulge in self-medication. Due to change in education and social structure, the secrecy of prescription had become old fashioned. In recent times, the doctors are instructed to write medicine names in capital letter with clarity to avoid medication error in prescriptions (Davis and Cohen 1981). Calculations errors can happen leading to a medication error while calculating and converting the medication in terms of quantity, for example, when a patient is prescribed 300 micrograms of medication which is available in strengths of 1 mg per ml. The pharmacist should be able to prepare the strength of the medication and should dispense with proper instruction. The monitoring involves observation of the patient after administration of the medication for expected outcomes and not causing any harm to the patient. Failure to monitor side effects and expected outcomes is one of the major causes of medication error. The risks of medication error are very high in patient with polypharmacy (in geriatrics), renal impairment, and pregnancy and in children and neonates in whom dose calculation is required. It is very essential to take extra precaution when medications with high risk are prescribed, for example, drug with narrow therapeutic window (digoxin). Medication like rifampicin and potent medications like fentanyl need a careful monitoring. Complex doses and therapeutic drug monitoring

46

A. N. Nagappa and V. Naik

schedules are required for treatments with warfarin, insulin, neuromuscular blocking agents, aminoglycoside antibiotics, intravenous potassium, and emergency medications (Berdot et al. 2012). The patient’s education and knowledge play a special role in making patient a participant in his/her own therapy. It is the responsibility of the pharmacist to learn from the patient regarding the gaps in knowledge of patient. Although there is no need for detailed scientific knowledge of the drug he has been prescribed, he should be able to tell the name of drug he is prescribed. How the medicine is helping him in his disease condition? In other words, the patient should know why the particular medicine is prescribed for his/her. In addition, the patient should also be well versed with probable ADR of medicine he/she is using. There are several lifestyles that patients need to practice while on medication. The knowledge of side effects, special precautions, dose, administration, and the regimen is very essential for the patient safety in the community setting. The explanation with effective audiovisual tools and pictograms perfects and boost patient confidence self-management of his/her condition. Using memory aids is of great help in prevention of medication error due to forgetfulness. Text, books, and personal digital assistant app reminders are very much useful in preventing medication error due to lapse in memory. Setting of alarms to remind the time of dose by mobile phone can eliminate missing of a dose. However, making a protocol of treatment being stored in memory devices, one can readily reckon the protocol and adhere to the treatment scheduled. Making patients get involved in his treatment is the key to the success of treatment. The patient should be counseled about the name of the drug, purpose, and mechanism of action along with the dose and route of administration and schedule to help in mitigating the tension of the patients. Encouragement of the patients to keep a written diary of medication, allergies, and diet chart is of great help to build the patient history in terms of disease management (Table 4.2). The various stages of prescription orders and dispensing comprise of the following in the order of activates.

4.5

Ordering, Prescribing, Documenting, Transcribing, Dispensing, Administering, and Monitoring

Medication errors are most common in the ordering or prescribing stage. Typical errors by the healthcare professional are writing the wrong medication, wrong route wrong dose, and the wrong frequency. These ordering errors account for almost 50% of medication errors. Data show that nurses and pharmacists identify anywhere from 30% to 70% of medication-ordering errors. It is obvious that medication errors are a pervasive problem, but in the majority of cases, the problem is preventable and detectable by pharmacovigilance and therapeutic drug monitoring.

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

47

Table 4.2 Look-alike and sound-alike names reported to the ISME MERP from July through September 2010 Depakote (divalproex sodium delayed release) Dexamethasone Doribax (doripenem) DTaP (diphtheria and tetanus toxoids, and acellular pertussis) LaMICtal (lamotrigine) Morphine sulfate Oxycodone Pitavastatin Risperidone Sulfadiazine Tramadol Zolmitriptan

Depakote (divalproex sodium delayed release) Dextromethorphan Zovirax (acyclovir) Durezol (salicylic acid) LamISIL (terbinafine hydrochloride) Morphine sulfate extended release OxyCONTIN (oxycodone hydrochloride extended release) Pravastatin Ropinirole Sulfasalazine Trazodone Zolpidem

ISMP ¼ Institute for Safe Medication Practices; MERP ¼ Medication Errors Reporting Program. Adopted from Pharmacy Times; Look-alike, Sound-alike Drug Names, December 13, 2010, Michael J. Gaunt, PharmD.

4.6

Causes of Medication Errors

The understanding of medication errors has changed and is believed to be a systemic problem happening undeliberate. Errors in the system may be viewed as the end result and not the cause. Thus, rather than focusing on changing the behavior of every healthcare worker, hospitals are now trying to understand how the system has failed in identifying the medication error. This approach is designed to introduce barriers and safeguards at every level so that a mistake can be prevented before the drug is given to the patient. In many cases, mistakes are made by some of the welltrained healthcare professionals, and rather than blame them, one should try and understand why the error occurred. In many cases, errors occur in recurrent patterns, irrespective of the healthcare workers involved (Al et al. 2011).

4.7

Distractions

In the hospital setting especially emergency/ICU surgery wards, doctors and nurses are stressed due to over burden of workload; the scenario of the ward can be best described as a situation in a busy railway station or bus stand where the operational management needs continuously. In the ward room, there will be several beds with the entitlement of different doctors and patient with disease. The treatment should be given timely with correct medicines and dose in such situation; the requirement of the healthcare professional will be large, and there is likely possibility of distractions

48

A. N. Nagappa and V. Naik

for the doctor. It is advisable to maintain calm and peaceful environment and train well healthcare professional to deal patiently with the patient in the ward while patient is being treated. The management of destruction and maintaining calmness in order to minimize medication errors are very important. One of the major causes of medication errors is a distraction in different way. Nearly 75% of medication errors have been attributed to this cause. Physicians have many duties in a hospital (e.g., examining patients, ordering laboratory and imaging studies, speaking to consultants, rounding on their patients, speaking to patient family members, conversing with insurance carriers before ordering studies), and in the midst of all this, they are often asked to write drug orders and prescriptions. In the hurry to be done with the duty of writing drug orders, sometimes a lapse of judgment develops, and a medication error occurs. It can also happen to the best physician. Sometimes the physician may be on the phone, and a clinician may be standing with the order chart next to him or her asking for a drug order. Quickly, the physician may scribble in a drug order, not paying attention to the dose or frequency. It is the unscheduled events in the life of a healthcare provider such as the constant pages, attendance at meetings, and answering telephone calls that disrupt patient care. Many physicians do not acknowledge that these distractions are a problem, but in reality, these distractions are often the cause of medication errors and should be paid attention to manage (Getnet and Bifftu 2017). To minimize distractions, hospitals have introduced measures to reduce medication errors. Most hospitals are working on ways to decrease distractions to ensure that medication errors do not occur. For example, physicians are urged to order drugs at a set time after ward rounding on their patients; this is a time when they also write their daily progress notes. Other clinicians are requested not to disturb the physician at this time of the day. In addition, clinicians are asked only to disrupt the physician for an emergency call. In addition, physicians are being urged to develop a structure for their patient care that is organized so that distractions are limited. While answering a page is often necessary, many hospitals recommend that physicians not to answer patient calls until patient duties are completed. In addition, healthcare institutions are now penalizing physicians who continue to have too many medication errors because of distractions; the end result is a restriction in prescribing privileges. Of course, not all distractions can be eliminated because the practice of medicine is itself unpredictable and chaotic at the best of times.

4.8

Distortions

A very common cause of medication errors is distortions. The majority of distortions may originate from illegible writing, misunderstood symbols, use of abbreviations, or improper translation. A significant number of healthcare providers in the United States are from foreign countries and often write orders for medications that are not even available domestically. When a practitioner questions the drug, the physician often asks the nurse or pharmacist to substitute the medication prescribed for a

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

49

similar drug. This type of distortion can lead to major errors because neither the non-prescribing practitioner nor the pharmacist can substitute a drug. All hospital pharmacies have a list of medications available in the formulary, and doctors should know what is available and limit the ordering from this list (Tariq et al. 2021).

4.9

Illegible Writing

Illegible writing has plagued both nurses and pharmacists for decades. Physicians are often in a hurry and frequently scribble down orders that are not legible; this often results in major medication errors. Taking shortcuts in writing drug orders is a prescription for a lawsuit. Often the practitioner or the pharmacist is not able to read the order and makes their best guess. If the drug required is a dire emergency, this also adds more risks to the patient. To eliminate such errors, most hospitals have rules that practitioners and pharmacists have to follow; if the drug order is illegible, the physician must be called and asked to rewrite the order clearly. The practitioner or the pharmacist should never take a guess at what the drug/dose is. The bad writing by physicians has become such a major problem that the Institute for Safe Medication Practices has recommended complete elimination of handwritten orders and prescription. This problem has been resolved with the use of electronic records where everything is typed, and poor writing is no longer an issue; however, errors still can occur from writing the wrong drug, dose, or frequency (Brits et al. 2017). Approach Every Prescription with Caution In the last decade, there have been many new drug releases, and generics with similar names have flooded the market. In addition to having similar names, many of these medications have multiple uses and alternative names. If the diagnosis is not stated on the prescription, there is a risk that the drug may be prescribed for too long or an inadequate amount of time. With dozens of new generics with similar names, the risk of error is very high. To counter the consequences of unintended substitutions for medications, the US Pharmacopeia has listed the names of look-alike and sound-alike medications, and the Institute for Safe Medication Practices has developed a list of abbreviations that are routinely misinterpreted. Write Down the Precise Dosage Distortion of dose can easily occur when nonspecific abbreviations or decimal points are used without thought. One abbreviation that is often the cause of medication errors is the “Ug” symbol for micrograms. It is often mistaken for units and should be avoided at all costs. It is best to spell out the quantity. Use of Metric Measures The use of apothecary measures is now part of the historical archives; weight measures like grains, drams, and minims have little meaning to the modern-day healthcare workers and should no longer be used. Instead, use the universal metric measures that are preferred by pharmacists and practitioners. When using metric measures, be careful when and where you use the

50

A. N. Nagappa and V. Naik

decimal point. For example, when writing dexamethasone 2.0 mg, if the decimal point is not visualized, then the nurse or the pharmacist may think it is 20 mg. On the other hand, a zero should always precede a decimal point. For example, when writing digoxin, it should be written as 0.25 mg and not just 0.25 mg. Again, if the decimal point is not seen, it can easily lead to a tenfold increase in dose. Consider Patient Age The two populations that are very sensitive to medications are the elderly and children. Always check the patient’s age, body surface area, and body weight to ensure that the dose administered is correct. In addition, if you write a prescription, write the age and weight of the patient on it so that the pharmacist understands how you derived the dose. In children, most drugs are prescribed based on body weight, age in months and years, and body surface area. Liver and Kidney Function Another very common reason for medication errors is not taking into account renal or liver failure. Patients with renal and liver dysfunction need lower doses. Otherwise, toxicity can result because of the failure to excrete or break down the medication. Provide Directions Healthcare workers who write drug orders and prescriptions should never assume that the other party knows what you mean. Provide clear instructions on doses, the number of pills, and how and when the medication is to be taken. Writing orders like “take as directed” is a recipe for disaster. Similarly, “PRN” without an indication should never be used. It is an error in the making. Write down when the drug is to be taken and for what purpose (e.g., take 2 mg of morphine by mouth for pain. Take the morphine every 3–4 hours as needed for pain). Reducing medication errors requires open communication with the patient and the pharmacist. Use of Abbreviations One very common cause of medication errors is the use of abbreviations. Often the route of administration is abbreviated using suffix like QD, OS, TID, QID, PR, etc. QD (meaning once a day) can easily be mistaken for QID (four times a day). Additionally, these abbreviations can have several other meanings and can be misinterpreted. It is recommended that abbreviations not be used at all when writing medication orders instead to be written clearly. Duration of Treatment In the past, some physicians would simply write down the total number of pills that a patient is supposed to get without specifying the duration of treatment. It is vital to specify the duration of treatment and that the duration of treatment matches the number of pills prescribed. In addition, when writing about the quantity of the drug, it important to write down the actual number of pills (e.g., 90) rather than stating dispense for 2 months. Another reason for specifying the number of doses is that it requires the patient to comply with follow-up which prevents them from just collecting older medications. If the patient has a chronic disorder, the practitioner should be treating each flare-up as a single event with a finite number of pills. If the patient has a flare-up or exacerbation, tell him or her to come to the clinic for an exam and at that time determine if more pills are needed.

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

51

Just empirically prescribing pills for a theoretical recurrence only leads to confusion and a high risk of adverse reactions. Remain Alert for High-Risk Medications For example, if a patient has a deep vein thrombosis or a prosthetic heart valve and requires warfarin, only prescribe for 4 weeks at a time and reassess the patient with therapeutic drug monitoring on each visit. Do not give warfarin for many months at a time. The patient needs to be monitored for the INR, and the dose may have to be adjusted. Always Specify the Indication for the Drug Writing the indication for the drug is highly recommended because many drugs have multiple uses. Unfortunately, the majority of prescriptions never have the diagnosis written, and omitting this information increases the potential for complications. Writing the diagnosis informs the pharmacist of the diagnosis and reminds the patient of the medication’s purpose. This small step can facilitate counseling by the pharmacist, reinforce the patient’s treatment plan, and provide ample opportunities for patient education. It also helps improve communication between the healthcare provider and the pharmacist. For example, corticosteroids and anticonvulsants have many uses, and it is important for the pharmacist to know what condition is being treated. An anticonvulsant may be used to treat a migraine, neuropathic pain, or behavior, besides seizures. Choose the Appropriate Drug for the Patient Population When dealing with elderly patients, healthcare providers should avoid ordering drugs listed on the Beers criteria – this list of drugs is known to have the potential to cause adverse reactions in elderly individuals, as elderly patients have decreased pharmacokinetic parameters. Add Supplemental Instructions Always add extra precautions when necessary. For example, when prescribing tetracyclines, the patient should be warned about sun exposure and pregnancy about fetal damage, or when taking ibuprofen, the patient should be told to take the medication with food. When prescribing metronidazole, warn the patient about alcohol use. Do not assume that the pharmacist will add these extra warnings when dispensing the drugs. For patients who cannot read or understand the instructions for prescribed medications, educate the family and provide verbal counseling when required. Adopt a Reporting System The only way to reduce medication errors is to develop a reporting system and then make changes to prevent similar errors from reoccurring. Even a near miss should be reported. The staff should be encouraged to report without any repercussions. It is a great learning experience and enhances safety. The awareness of drug adverse reaction reporting by patients should be created. Discuss the Patient’s Preferences Considering the many drugs available to treat the same disorder, involve the patient in the decision-making. The patient should be told about the potential adverse effects, precautions, storage, administration, and contraindications of the drug.

52

A. N. Nagappa and V. Naik

Write Your Contact Number Many healthcare providers write prescriptions or orders in the chart and often do not leave a contact number. If there is a query about the drug, then the pharmacist and nurse are left on their own, and consequently, the patient misses out on the medication. This helps patient in clearing the query about the drug.

4.10

Who Is to be Blame: The Healthcare Professional or the System?

In the past when medication errors occurred, the individual who caused it was usually blamed for the mishap. Medication errors related to employees may be due to the following:

4.11

Other Issues

4.11.1 Other Strategies to Reduce Medication Errors Over the years, hospitals have developed strategies to prevent medication errors. Some of these strategies include the following: • Double check dosing and frequency of all high-alert medications. A list of highalert medications is provided by the Institute for Safe Medication Practices. • If unsure about the drug or the dose, speak to the pharmacist. • If the writing is illegible, do not give the medication in the belief that you think you know what it is. Call the healthcare provider to confirm the drug or dose. • Recheck the calculation to ensure that the patient will get the right therapeutic dose. • Ask another clinician to recheck your calculations. Writing prescriptions and orders for medication is an everyday part of the job for many healthcare workers. However, the increased demands to see more patients who require many medications often become monotonous, and one can become careless. The majority of healthcare workers never anticipate an adverse drug event and, consequently, rarely check back with the pharmacists for drug interactions. With a high number of medication-related errors, healthcare workers are under great scrutiny to change their work habits and adopt a culture of safety when writing drug orders and prescriptions. Though there is no single way to eliminate all drug errors, healthcare workers can reduce the errors by becoming more cautious and interacting closely with other practitioners, pharmacists, and patients. Open and direct communication is one way to bridge the safety gap (Agrawal 2009).

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

53

Fig. 4.1 Medication errors

4.12

Preventing Medication Errors (Fig. 4.1)

• Always write one prescription for each medication. • Besides signing the prescription, always circle your name on the preprinted prescription pad. • Do not hesitate to check the dose and frequency if you are not sure. • Always consider the fact that each medication has the potential for adverse reactions. • Do not use drug abbreviations when writing orders. • Always add the patient’s age and weight to each prescription. • Check for liver and renal function before ordering any medication. • Spell out the frequency and route of dosage; do not use abbreviations. • Always specify the duration of therapy; do not say give out “XXX” number of pills. • Always be aware of high-risk medications. • Double check the prescription before dispensing. When writing a prescription, state the condition being treated.

4.13

Medication Errors and Its Impact on Outcomes

Medication is always accompanied with lot of adverse drug reactions; there is a cause of concern of morbidity due to ignorance and anxiety; patient ends up with mistake while using the medicines, modern medicines when administered to patient it is likely that medicine should be going to every nook and corner of the body where the blood goes. The cells of our body react differently when they are exposed to medicines depending on the nature of the medicine and the concentration of the medicine which largely depend upon the blood perfusion to the cell, tissue, organ,

54

A. N. Nagappa and V. Naik

Fig. 4.2 Medication error prevention

and system (Fig. 4.2). For example, drug known to reduce blood sugar may be leading to hypoglycemia and may cause disturbance in brain and muscle functions and if ignored can lead to severe damage to the brain and heart. One should be cautious while using medicines in general as patient and health consumers are not having complete knowledge regarding medicines and their effect on the human body. It may be single drug or may be combinations of medicines or polypharmacy. Patient and healthcare consumers must consult a knowledgeable registered pharmacist to learn about conditions for using the medicines prescribed. Medicines being sensitive to environmental conditions like temperature light and moisture, the storage conditions are to be met in the home in order to protect the medicines from deterioration and maintain its efficacy (Hillestad et al. 2005). Apart from the storage conditions, there are several conditions which need to be followed while using the medicines. For example, some medicines are having severe drug-drug interaction and drug-food interactions. These conditions need to be meticulously observed while using the medicines. For example, thyroxin sodium which is used in hypothyroidism should be taken on empty stomach, and one should not take any food or milk at least for 1 hour after ingestion. If the patient and HC are unaware of this condition although he is using the medicine, it may be not producing its effect. There are numerous episodes or examples where in medication errors are happening and patients are not aware unless instructed by pharmacist or fellow healthcare provider. There is a need to establish a system of avoidable; we have system approach for identifying, documenting, and improving the use of medicines among patient and healthcare consumers. Unfortunately, the medicines are not handled and presumed that they can cause no harm by the patient and healthcare consumers; hence they indulge in self-medication and irrational use of medicines, due to non-availability of identifying and documenting medication errors among the patients; the opportunities to improve the irrational use of medicines remain evaded.

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

4.14

55

Quality of Life and Cost of Treatments

The medical treatments have three-dimensional outcome, clinical, economic, and humanistic outcomes. These are well described in economic, clinical, and humanistic outcome model (ECHO) as shown in Figs. 4.2, 4.3, and 4.4. Measurement and quantification of all three dimensions shall give an idea about noticeable features of

Fig. 4.3 Echo model for health outcomes

Fig. 4.4 Health outcomes (clinical, economic, and humanistic) and sources of HEOR evidence

56

A. N. Nagappa and V. Naik

treatment. However, to get correct value of treatment integration of all the three outcomes, the three dimensions need to be done. Clinical outcomes are the outcomes based on measurement of the patient’s physical conditions like heart rate/blood pressers/biochemistry of the blood, ECG, MRI, and PET scanning. Clinical outcomes are used by physician to diagnose and asses the status of the disease and help the doctor to make a treatment strategy. The clinical outcomes are also considered as indicators of health and disease. The monitoring of the clinical parameter like blood sugar, blood pressure, or hemoglobin concentration is utilized to assess the status of health like diabetes mellitus, hypertension, and anemia (Cheung et al. 2009). In clinics, clinical parameters are considered highly valuable as this decides the strategy of treatment. They are over emphasized, and patients give more importance to normal value. They feel very depressed when clinical report goes very berserk. Patients develop anxiety and stress which worsens further. Clinical parameter is overfocused than economic and humanistic outcomes. The economic outcome and humanistic outcomes are also important because patient and his/her family should arrange money for treatment in the absence of health insurance coverage. The product centric market focuses on medicines, diagnosis, and medical devices driven by industrial promotion. In a product centric market, patient’s economic status and the quality of life are deliberately ignored, overlooked, neglected, and/or not given due importance. The pharmaceutical industry with its financial resources influences doctors to prescribe more medicines by giving them kickbacks. This has a very negative impact on prescription writing by the doctors, and the priority for prescription becomes primary over the patient quality of life. Repercussions of high impact promotions have led to the irrational prescribing and unethical practices by the doctors. The government and regulatory agencies are in constant efforts to control such activities. There should be a law and system for documentation and audit of prescription in order to bring transparency and accountability. The complaints regarding over prescribing and asking the patients to undergo various lab test and diagnostic are the common scenarios in private medical practice (Kozma et al. 1993; Langley 1994). Economic outcomes are measured as cost-benefit analysis, cost-comparison analysis, cost-consequence analysis, cost-effectiveness, cost-minimization analysis, cost of illness study, and cost-utility analysis.

4.15

Conclusion

To do error is human, but not in the healthcare systems. The error in healthcare delivery especially in pharmacy is not acceptable as it costs patients’ outcomes and healthcare costs. Medication errors are to be identified before they occur, and attempt to prevent should be made before it changes into serious adverse events. Properly trained pharmacist should scrutinize the prescription and check the database for probable drug-drug interaction and take appropriate actions to prevent occurring incidents.

4

Patients: Gaps in Knowledge, Medication Errors, and Their Impact on. . .

57

References Agrawal A (2009) Medication errors: prevention using information technology systems. Br J Clin Pharmacol 67(6):681–686. https://doi.org/10.1111/j.1365-2125.2009.03427.x Al-Jeraisy MI, Alanazi MQ, Abolfotouh MA (2011) Medication prescribing errors in a pediatric inpatient tertiary care setting in Saudi Arabia. BMC Res Notes 4:294 Berdot S, Sabatier B, Gillaizeau F, Caruba T, Prognon P, Durieux P (2012) Evaluation of drug administration errors in a teaching hospital. BMC Health Serv Res 12:60 Brits H, Botha A, Niksch L, Terblanché R, Venter K, Joubert G (2017) Illegible handwriting and other prescription errors on prescriptions at National District Hospital, Bloemfontein. South Afr Family Pract 59(1):52–55. https://doi.org/10.1080/20786190.2016.1254932 Cheung K-C, Bouvy ML, De Smet PAGM (2009) Medication errors: the importance of safe dispensing. Br J Clin Pharmacol 67:676–680 Davis NM, Cohen MR (1981) Medication errors: causes and prevention. Neil M. Davis Associates, Huntingdon Valley Gaur S, Sinha A, Srivastava B (2012) Medication errors in medicine wards in a tertiary care teaching hospital of a hill state in India. Asian J Pharm Life Sci 2:56–63 Getnet MA, Bifftu BB (2017) Work interruption experienced by nurses during medication administration process and associated factors. Northwest Ethiopia Nurs Res Pract 2017:8937490. https://doi.org/10.1155/2017/8937490 Hillestad R, Bigelow J, Bower A, Girosi F, Meili R, Scoville R, Taylor R (2005) Can electronic medical record systems transform health care? Potential health benefits, savings, and costs. Health Aff 24:1103–1117 Kozma CM, Reeder CE, Schulz RM (1993) Economic, clinical, and humanistic outcomes: a planning model for pharmacoeconomic research. Clin Ther 15(6):1121–1120 Langley PC (1994) Outcomes research and modeling therapeutic interventions for economic evaluations. Clin Ther 16(3):538–552 McLellan AT (2017) Substance misuse and substance use disorders: why do they matter in healthcare? Trans Am Clin Climatol Assoc 128:112–130 Patel N, Desai M, Shah S, Patel P, Gandhi A (2016) A study of medication errors in a tertiary care hospital. Perspect Clin Res 7(4):168–173. https://doi.org/10.4103/2229-3485.192039 Tariq RA, Vashisht R, Sinha A et al (2021) Medication dispensing errors and prevention. StatPearls Publishing, Treasure Island

5

Communication: Inter- and Intracommunication, Provider-Patient Communication, Perspectives and Approaches, Provider Competencies and Communication Skill, Patient Competencies and Communication Skills, Equity in Healthcare Delivery, Patient Counseling, Medication History, and Patient Education A. N. Nagappa and Vaishnavi Naik

Abstract

Communication in healthcare delivery is very valuable and quite different from general communication. In olden times, prescriptions were deliberately written in coded language and abbreviations in order to keep the secret of treatment. Gradually as time evolved, healthcare professionals felt the need for patients’ education, and education of patients became essential as the patient understanding of therapy is important since noncompliance of patients to therapy limits the scope of the outcomes. It is very essential to enhance patient cooperation and reduce the stress and anxiety of the patient. Keywords

Inter- and intra-professional communication · Medication history · Patient counseling · Patient compliance · Patient safety

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_5

59

60

5.1

A. N. Nagappa and V. Naik

Communication: Inter- and Intracommunication

Health communication is the study and practice of communication and promotion of health information. Health communication can happen by public campaigns, health education, and communication between healthcare providers and the patient and healthcare consumers. The motto of health communication is to build health literacy among patients and healthcare consumers so that they will be able to choose appropriate health approach among available choices. Effective health communication can only be achieved when it is customized to the individual patient need. Diabetic health camp patients are provided with the information which they ask for, and the pharmacist identifies gaps in the patient knowledge. Diabetic camp may also be focused on assessing the complication of diabetics such as retinopathy, nephropathy, and neuropathy. It may also be extended for assessing the status of cardiac health and neurology (Finset et al. 2020). Health communication aims at increasing patients’ and healthcare consumers’ knowledge and awareness of current health issues; for example, awareness of viral hepatitis makes patients and healthcare consumers change their habits which help in the prevention of the spread of hepatitis. Patients’ and healthcare consumers’ behaviors and attitudes can be influenced by the health communication; for example, recent viral diseases like HIV, dengue, swine flu, and Ebola are causing damage and death to the patients. There is a need for public campaign and health education so that people can avoid exposure to diseases. The motivations of patients and healthcare consumers to adopt healthy practices offer a formidable challenge; here demonstration is somewhat effective in influencing to shun unhealthy practices and adopt healthy lifestyle. For example, to shun open defecation and change the behavior to use toilets is a formidable challenge, and the public health agencies struggle in order to convince patients and healthcare consumers by highlighting the consequences of unhygienic practices and association with diarrhea and worm infestation. Even diseases like typhoid and cholera may spread which can be curtailed by avoiding open defecation and adopting toilets (van der Bles et al. 2020). For the implementation of advocacy of health issue or policy health, communication plays a vital role. The advocacy usually uses celebrities like film artists and sports persons to send the messages effectively to patients and healthcare consumers. It is also important to create a demand for health services as it is usually being observed that P&HC do not reach out for health facilities. Although it is made available due to lack of awareness or motivation, in such circumstances, health communication plays a vital role in creating demand or support for health services. It is also Observed in communities that there are many myths and unscientific practices looming over ignorance of patients and healthcare consumers. Health communications with effective campaign managers work hard to bust the myth and misconceptions about diseases or health. The pharmacist has to communicate with patients and healthcare consumers while dispensing prescription medicines. The pharmacist should also acquire skillset and deliver with due diligence without spending more time. Patients and healthcare

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

61

consumers do not like to spend time in listening to the advice of the pharmacist. The pharmacist should adopt quick effective mode of communication and should leave a strong impression with patients and healthcare consumers regarding the health information. The mode of communication may be either oral instructions, written notes, printed leaflets, audio messages, video massages, or hoarding and billboards. The preparation of an effective communication material and its delivery in short time are the demand of patients and healthcare consumers. The health communication intervention helps patients and healthcare consumers in updating their knowledge and achieving health through continuous communications. Interpersonal communications are the basis of patient-centered care. Clear communications and patient’s outcomes go hand in hand. Poor communications between the pharmacist and fellow healthcare providers lead to medication error. Failed communication may promote unsafe use of medication. The pharmacist is responsible for not only dispensing but also educating the patients about safe use of medication. The importance of interpersonal communication is the basis of building a trust among patients and pharmacists. Although interpersonal communications seem easy, during practices one soon realizes the challenges and skill sets essential for delivering interpersonal communications in pharmacy practice which is a lifelong engagement. We shall look at the professional responsibility of a pharmacist towards the patient care. Pharmacists are placed in the position where they can contribute and improve the patient care by reducing the medication error and improving the use of medications. To achieve this goal, effective communication skills are required. It is the responsibility of the pharmacist to identify an adverse drug event by looking at the prescription and brief the interaction with doctor. He/she should refer back the patients to doctor to correct the prescription. It is observed that in the field of healthcare, product-centric activities dominate over patient-centric care. In the product-centric care, doctors and fellow healthcare professionals become part and parcel of marketing the product instantly looking at the patient needs. The environment of product-centric marketing has overshadowed the pharmacist role and pharmacy practices. The drug laws and regulations although in enforcement are not implemented. The silence of enforcing authorities and negligence of patients have led to a situation-conducive environment for manufacturers, doctors, and pharmacists. Lack of transparency and accountability of healthcare providers has led to chaos in healthcare delivery. However due to repeated failures and medication error, the conciseness regarding patient safety is slowly gathering momentum. Change from drug-centric care to patient-centric care needs to be increased and supported by government regulations, by promotion in mass media, and by efforts by NGOs. The patient-centered communication in pharmacy practice begins by assuming the responsibility of patient care by the pharmacist. The pharmacist in charge shall volunteer for the role of providing maximum impossible safety information and focuses on quality outcomes for the patients. Patients who come to the pharmacy for filling the prescription usually have a lot of confusion and anxiety regarding the disease and the medications prescribed to

62

A. N. Nagappa and V. Naik

him/her. If patients in such state of mind visit pharmacy to fill the prescription and if the patient feels shy, guilt, or any other discomfort, then he/she cannot communicate confidently with the pharmacist. He/she usually tries to avoid the pharmacist and expresses a lot of distress while purchasing the prescription medications. The pharmacist should be expecting the mental status of the patient and act responsibly by facilitating the patient giving him/her the confidence of trust and goodwill. Promise of care and comfort should be expressed through body language and gestures (Jalal et al. 2018). It is the skill of the pharmacist to observe the patient and his/her needs. He/she should appropriately open up dialogue with a greeting and goodwill gesture. Expression of the pharmacist should build confidence in the patient and feeling of promise of care. Communication plays an important role in making the patient understand the various important dos and don’ts while using the medication. Especially regarding the doses and regimens, there have been many episodes of drug accidents reported due to poor communication by the healthcare provider about how to use the medicines. The pharmacist being the final healthcare professional in the healthcare chain has to take extra precaution that the patient has understood and is capable of using the medicines as per the instructions. There are many types of perceptions in the patient’s mind. In many states due to lack of communication, a vaginal tablet is consumed orally by the patients. Every medicine and doses have a unique condition of use which needs to be instructed to every patient while dispensing. It may look very simple and obvious for the pharmacist, but for the patients, it is very important as many drug accidents are reported in practice due to lack of patient information regarding how to use. It is also very important to interpret the patient’s understanding and perception. Regarding the use of medications, patient’s perceptions depend upon various aspects of the background, history of the disease in the patient, and expectations of the patient from the medicines. It is always recommended to ask the patient to explain the process of medication use and observe for any lapses and omissions in the procedures. The deviations are identified and corrected by appropriate demonstration and counseling (van der Bles et al. 2020; Jalal et al. 2018). Asserting the active role of patients plays an important role in pharmaceutical care. Patients are to be trusted and encouraged to observe the therapeutic monitoring of their condition by following the signs and symptoms of the disease; for example, patients with diabetes are to be trained in observing the changes in their condition in response to drug administrations. Documenting the parameter of blood sugar levels, blood pressure, and body mass index shall give an idea regarding the effectiveness of the current treatment. This will empower the patient in his/her own healthcare management making the patient responsible and active in healthcare practice. This would help in overcoming the issues of patient compliance and adherence to therapy. The patient begins to feel confident and positive towards his/her health and wellbeing.

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

5.2

63

Provider-Patient Communication Perspectives and Approaches

There might be significant difference between various health delivery systems and the environment in which they operate. For example, in some systems, healthcare may be subsidized by the government, and in some it may not. Also, some systems have stronger infrastructure than others in the form of staff, technology, and overall resources employed. Besides these, various other factors such as the overall ratio between the number of patients and number of physicians treating them and many sociocultural factors may also influence the way a healthcare system functions. However, the key aspects of patients seeking health-related solutions and health professionals providing those solutions remain the same across systems. From this perspective, the relationship between healthcare providers and their patients forms the core of any healthcare delivery system (Berman and Chutka 2016). The vital contributor of the relationship is the communication between provider and patient and the understanding of each other’s needs, expectations, and constraints that form the basis of the communication. In most healthcare delivery environments, the focus is more on providers, and not much emphasis is given to the receiver, i.e., the patient. For example, an effective physician is not only a provider of health/treatment information but also a caregiver and health educator. The quality of interaction between the provider and patient may have a far-reaching influence on the efficacy of treatment and on the overall efficiency and cost-effectiveness of the healthcare system. From this perspective, understanding of this communication process and other contributing sectors may not only improve the quality of care but also make health delivery process more efficacious and efficient (Consultation Skills for Pharmacy Practice 2014).

5.3

Provider Competencies and Communication Skill

One of the primary drivers of effective provider-patient communication is the provider. In provider-patient communication environments, provider generally has more control over the relationship, and it is important that the provider is aware of the factors that may result in effective communication and related positive health and socioemotional outcomes. Studies suggest that competent physician communication consists of addressing both cognitive and affective processes. Here Cognitive processes involve referring to information seeking and giving; affective processes refer to relational communication focused on understanding the patient’s feelings and emotions and on developing a trusting relationship. This indicates that physicians have to be aware about the elements of relational communication as well as effective ways to elicit information from patients so that he/she can provide tailored information based on patient values. This involves an understanding of effective communication behaviors and theoretical frameworks that may help the physician gain understanding of the patient’s values and then create massages based on that understanding.

64

A. N. Nagappa and V. Naik

The Primary Objectives—in terms of patient’s communication—may be conceived as creation of effective interpersonal relationships, information exchange, and treatment-related decision-making. Primary outcomes may be conceived as patient satisfaction, patient compliance, comprehension and memory of health information, and physiological, behavioral, and subjective health outcomes. Communication behavior in this context may consist of seven essential components that are mentioned below. 1. 2. 3. 4. 5. 6. 7.

Task-focused behavior Affective behavior Verbal behavior Nonverbal behavior Handling privacy expectations Relationship control Communication vocabulary

Task-focused behavior encompasses communication that focuses on the technical aspects of communication like interaction about diagnosis and description of disease and treatment options. Affective behavior involves communication about the patients’ feeling and emotions and display of sympathy and sensitivity to his/her values. Verbal behavior involves effective verbal communication in a structured, organized way so that the patient is able to develop understanding of his/her medical situation and choices and nonverbal behavior involves elements like tone of voice, eye contact, and body posture along with verbal and affective communication behaviors. Nonverbal communication also plays a crucial role in communication. For example, if a physician talks about a patient’s feelings while looking away from him/her, it may be construed as insincerity and lack of care and concern. Handling privacy expectations is another important element for building trust between physicians and patients. Physicians may need intimate information from the patients and may also need to touch or examine the patients during medical interactions. Any behavior by the physician that may be perceived by the patient as aggressive and violation of privacy may negatively influence the interaction outcomes. Therefore, the physician needs to ensure that such intimate behaviors and information gathering are sensitive to patient’s autonomy concerns. Relationship control refers to physician’s control of relationship during interaction; more control by the physician involves domination of conversation by him/her without much emphasis on patient’s contribution, whereas lesser control may facilitate a more partnership-oriented approach. Domination during interaction by the physician may restrict the patient from sharing information about his/her needs and emotions and may cause a barrier to successful relational communication. Communication vocabulary refers to the language used by the physician to provide health information. Physicians may think about health-related issues in medical terms that may not be comprehended well by patients; therefore, it is

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

65

Fig. 5.1 Communication model

important for physicians to use everyday terms while communicating with patients that may enhance patients’ comprehension and understanding of the health situation and make the patient more open and receptive to communication. Communication model is presented in Fig. 5.1. From the perspective of communication skill straining for physicians, Hulsman, Ros, Winnubst, and Bensing proposed a more specific typology of communication behaviors. They categorized these behaviors as behaviors specific to eliciting information. Behaviors specific to providing eliciting behaviors involve listening to patients actively without interruption, encouraging the patient to provide information in a respectful manner, eliciting information through open-ended questions, and involving the patient in the treatment process by asking for his/her opinion. Information-providing behaviors involve using nontechnical terms, educating and informing patients, and helping patients cope up with stress and anxiety caused due to disease-related uncertainty. Behaviors targeted at relational and emotional communication involve displaying empathy and concern with the patient’s problems, eliciting patient’s value and expressing understanding, and displaying warmth and caring attitude towards patient’s needs and problems through verbal and nonverbal behavior. Similarly, in the pharmacist-patient communication environment, participative behavior and interpersonal communication form the foundation for effective communication and relationship building. Since the role of the pharmacist is different from that of the physician in the healthcare delivery process, though the dimensions of the relationships remain similar, the nature of communication and communication skill may differ. The key skills for developing effective relationship are information sharing, responsible behavior, patient centeredness, and effectiveness of interpersonal communication. Here information-sharing skills refer to communication with patients about medication issues like side effects of medication, combining medication with other prescriptions, and eliciting information about medication issues. Responsible behavior involves expressing willingness and interest in helping

66

A. N. Nagappa and V. Naik

patients with medication management and any other medication-related concerns. Patient centeredness involves demonstration of willingness to participate by listening to the patient’s questions and being sensitive to the patient’s values, and interpersonal communication involves encouraging behaviors like greeting patients and initiation communication that may make patients more comfortable about expressing their needs and concerns (Odhayani and Ratnapalan 2011). Understanding of communication behaviors makes providers more aware and may help them use these elements in a strategic manner. Another fundamental issue is eliciting and processing patient information involving sociocultural and other expectations. Knowledge of relevant social science and health communication theories may provide frameworks through which providers can develop strategies for seeking and providing information effectively. Though various frameworks from health counseling persuasion and health communication literature like the concept of self-efficacy from social cognitive theory, health belief model, theory of reasoned action, theory of planned behavior, and stages of change model may be used for this purpose, only the theory of planned behavior is discussed in this chapter since it covers a large part of variables and processes considered in other models. Theory of planned behaviors emphasizes three primary elements—attitudes, subjective norms, and perceived behavioral control as predictors towards the intention to perform a behavior. Here, attitude refers to patients’ positive or negative evaluation of the treatment and the disease. A strong attitude towards the treatment may be formed only when the patients are aware that the health problem needs attention and therefore adhering to treatment is important; information provided by the provider and discussion of the health condition may lead to stronger attitudes towards the treatment and medication. The next component, subjective norm, takes into account perceived influence by important others in the society such as friends and family. High subjective norm towards a treatment may imply that the patient believes that important others want him/her to address his/her health issues and he/she is willing to comply with their wishes. By seeking information about subjective norms, providers may gather information about sociocultural factors and influences relevant to the patient’s health behavior. While discussing treatment, the provider may use this information to discuss choices that may better suit the patient’s sociocultural values. The third component, perceived behavioral control, is similar to the concept of self-efficacy, which is considered to be one of the most important factors in influencing health behaviors. Perceived behavioral control refers to the perception of being able to perform a health behavior successfully. In the health context, it can be conceptualized as patient’s confidence in being able to perform the treatment of recommended health behavior successfully to address the health condition. Providers may discuss with patients if they will be able to successfully follow the physician’s recommendation and seek information about any barriers. These barriers may be rooted in numerous sociocultural or economic factors or in other constraints related to the patient’s life. For example, patients might not be able to follow instructions because they do not understand them or they do not have enough financial resources to follow the recommendation. Each patient may have a unique

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

67

set of perceived barriers, which may be elicited by the provider and addressed to enhance patient satisfaction, compliance, and other health outcomes.

5.4

Patient Competencies and Communication Skills

Provider-patient communication is an interactional, bidirectional process, and both the provider and the patient may influence the nature of interaction and the relationship between them. Recent research has indicated the importance of patients’ communication behavior and training to influence the provider-patient interaction and related outcomes. From the bidirectional communication perspective, patient’s participation in the communication process enables the provider by providing an effective assessment of the patient’s values and expectations. Numerous studies involving patient training have shown patients’ communication skills to be a crucial contributor to effective patient-centered communication. Patient training research identifies three primary skills that may contribute to better communication between the physician and the patient. These skills are information seeking, information provision, and information verification. Information seeking involves the patient eliciting information from the physician. This may be in the form of direct or indirect questions. A question such as can you tell me how long it will take for me to recover is an example of a direct question; indirect questions refer to situations when the patient’s queries do not follow the direct question format. For example, a patient might say, “I am also feeling a slight numbness in my left leg sometimes. I cannot walk, or these days when I wake up, I feel dizzy, I don’t know why?” In these cases, though the patient is not asking direct questions, he/she is seeking information in a relatively indirect manner. It is important that the provider identifies these questions during the communication (Kerr et al. 2021). Information provision refers to the willingness and skill of the patient to provide information related to health and other socioemotional and sociocultural factors. This information may be provided as a direct response to the provider’s questions, as an elaboration of a direct response, and as information that is not asked by the provider but the patient finds important. For example, if a physician asks a patient if he/she exercises, the direct responses would be yes/no. An elaboration of this response may involve the patient providing more information about exercising habits, like the nature of exercises or conditions under which he/she might exercise and conditions in which he/she may not exercise. A patient may also provide unsolicited information like stressful work environment or family-related stress that may not be a direct response but may help the provider better understand patient’s values. Information verification refers to patient’s communication that may focus on clarifying information provided by the physician, ensuring that the patients correctly understand the information provided by the physician by repeating it or rephrasing it, and verifying information the patient may expect to receive in the future (Schwartzman et al. 2013).

68

A. N. Nagappa and V. Naik

Pharmacist and Patient communication, research has shown information sharing, responsible behavior, communication demonstrating active role taking, and interpersonal communication to be the key dimensions for relationship development. Enhancing competency communication on dimensions through patient training and education may result in effective pharmacist-patient communication and may improve health outcomes. Information sharing involves the patient providing information about medication issues to the pharmacist. These issues may involve information about the medication patient is taking, problems with medication, information about medication from other pharmacies and alternative medicine system, and information about allergies or side effects patients may be experiencing. Responsible behavior involves following the medication as directed and communications with the pharmacist about issues such as not understanding the directions that may influence patient’s medication adherence (Svensberg et al. 2018). Behavior showing active role taking involves being sensitive to pharmacist’s constraints and communication of medication issues when they arise. For example, if the pharmacist is busy when the patient visits the pharmacy, the patient may wait till the pharmacist is free. The interpersonal communication dimension involves creating an environment conductive to participative relationship by verbal and nonverbal behaviors such as greeting the pharmacist and initiating conversation.

5.5

Equity in Healthcare Delivery

In modern times, management of health requires not only inputs of drugs but also supplementation with indicated lifestyle and diet. The conventional way of handling of the diseases has been proved to be ineffective as overdependence on drugs alone resulted in counterproductive results. In drug-centric market healthcare model, healthcare providers and pharma industries have assumed key roles in the promotion of sale of medicines. It was soon realized that more medicines mean more diseases and less health. Polypharmacy has improved the sale of medicines but has not achieved health for patients and healthcare consumers. The chronic conditions which are currently in epidemics proposition demand knowledge, inputs, and adoption of corrective measures which can restore health. Taking the example of diabetes, the participation of doctors, nurses, pharmacists, and counselors has become essential in order to manage the diseases effectively. Doctors need to examine the patient thoroughly for signs and symptoms of eyes, heart, kidney, and neuron functions. Doctors should take appropriate measures to prevent further damage to the organs. Doctors can adjust the dose and change the medication in order to control blood sugar levels. For regular monitoring and management, a team comprising doctors, nurses, and pharmacists has to check the patient and document the status of the patient’s conditions. The physician has to refer to the ophthalmologist to observe for the development of diabetic retinopathy; similarly diabetic food cardiac evaluations and neurological pain have to be referred to the respective experts. The inputs of all these doctors are

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

69

very much essential for the management of diabetic conditions. Similarly, physiotherapists, nurses, and pharmacists need to contribute effectively as per their professional practice for the management of every disease. Hence, the current model of healthcare delivery mandates participation of all healthcare professionals resulting in a team approach in which the patients are also to be included. The role and responsibility of each healthcare professional define the exact equity in healthcare delivery; days of product-centric care are being replaced by patientcentric care in which equity in healthcare and by team approach is found to be more effective and productive.

5.6

Patient Counseling

The ethnic socioculturally diverse people live together in a community; they also belong to different socioeconomic classes like lower, middle, and upper categories. Further they are divided on the basis of their education, gender, age group, etc. They speak different languages and communicate in a multifold manner with different sets of background situation; for example a person going for buying grocery from the market and a person visiting the temple for his/her prayers should be having different mental preparedness and are likely to perceive the situation and respond in different manners. This diverse pool of people who represent the patient community have different needs and requirements of education and counseling. The needs of patient counseling are obviously diverse, requiring a highly competitive skill set for the pharmacist who is supposed to counsel the patient for safety and good outcomes of the therapy. The stages of patient counseling necessarily involve the following steps. The communications in patient counseling are usually one to one, wherein elements of communication are important. The first steps involve setting the stage for communication that involves inviting the patient with encouraging smile with a good body language of openness and trust; patients usually respond positively for such interaction and will be ready to open a dialogue and ask their doubts; the pharmacist should thoroughly exhibit such positive behaviors irrespective of the personal and professional grievances of the pharmacist himself/herself. If the patient is familiar with the pharmacist, he/she can encourage the patient by greeting him/her or welcoming him/her by personal names (Sanii et al. 2016). Advantage of active initiative by the pharmacist helps in removing the inhibitions of patients; this is usually because many patients are conscious about revealing their condition which they want to keep as secret; however, the pharmacist by his/her experience should be aware of the sensitivity of the patient and take care not to hurt the patient’s mentality; usually the patient comes to the pharmacy to ask several unanswered questions but they have difficulty in communication and struggle how to ask their doubts. Several times there is misunderstanding regarding the diet disease and drugs which they want to clarify from the pharmacist. They may come across

70

A. N. Nagappa and V. Naik

problematic experience during the treatment which they want to learn and resolve with the help of the pharmacist. It is also an opportunity for the pharmacist to train the patients to observe and monitor the outcomes of the treatment by counseling; there is no opportunity or time for the patient to share these issues and problems with the doctors. Hence the patient counseling in pharmacy is very important and gaining popularity among patients and healthcare consumers. The details of elements of interpersonal communication can be divided into five steps; first steps are about the sender who is the patient himself/ herself, who hands over a written prescription in the pharmacy; the message is decoded from the prescription which has instructions, list of medicines, dosage regimen, and patient who is the receiver; now the pharmacist discusses with the patient and tries to get feedback from the patient regarding the need of patient counseling. It is also needed to understand what type of barriers are present in the counseling; there may be language barriers or else there may be an issue of poor communication (Schnipper et al. 2006). After identifying the issue, the pharmacist using his/her skill and knowledge formulates a customized pharmaceutical care plan, which he/she implements by counseling.

5.7

Medication History and Patient Education

Medication history is the foundation of pharmacy practice and other healthcare services. Medication history can be taken for all kinds of patients including inpatients, outpatients, and ambulatory patients; it is the key to provide further care to a patient. Medication history begins with a dialogue with the patient or his/her attendant; it reveals the drug-taking habits of the patients, and history of disease the patient is suffering from; it usually happens so medication history is ignored and a diagnosis/prescription/pharmaceutical care is started; it usually leads to irrational treatment as the patient’s current use of medicines is not taken into account; for example if the patient is suffering from asthma and is newly diagnosed with high blood pressure and if a doctor in ignorance of the medicine history by chance prescribes a beta-blocker, the patient is likely to get a severe attack of asthma (Fitzgerald 2009). There are many instances of duplication of medicines and enhanced doses of medicines in case a patient is being treated by multiple doctors for different diseases he/she is suffering from. For example, a patient having clotting disorder is on bloodthinning medication containing warfarin. Such a patient visits pharmacy and asks the pharmacist for a medicine to get relief from headache. In such a circumstance, if the pharmacist dispenses a drug containing aspirin the patient may lose his/her life due to internal bleeding. This is because drug interaction results due to aspirin which displaces warfarin from his/her binding site. This causes sudden increase in the concentration of warfarin leading to massive internal bleeding; if the pharmacist had been alert, he/she would have asked the patient if he/she was on any medication and once the pharmacist knew the patient’s medication history, he/she would never dispense aspirin to such a patient (Ohm et al. 2013).

5

Communication: Inter- and Intracommunication, Provider-Patient. . .

71

Patient history is also important to know the conditions of the patients and calculate the doses required by the patient which is essential for preventing unnecessary exposure of high concentration of drug to the patient. The medication history is recorded while the patient is getting admitted to the hospital or while buying medicine from the pharmacy. The pharmacist tries to get information by enquiring the patient regarding his/her conditions and also previous and current medications along with the use of alternative medicines; patient history is also helpful in patient counseling because the pharmacist can obtain a great deal of information which gives ideas regarding the patient’s conditions and medications already being taken for other conditions (Alois and Jonas 1976). Patient education is important wherein the patient learns to inform the current medications and conditions to the pharmacist who in turn educates the patient about the medicines prescribed by the doctor, further works on the prescription, prepares the medicine kit, and describes in detail how to use the medicines and follow any possible ADR likely to happen in the course of treatment.

5.8

Conclusions

The changeover from product-centered care to patient-centered care has increased the scope of communication. There are various types of communication between pharmacist and pharmacist, and pharmacist and doctors and nurses, apart from patient counseling. The pharmacist, being an expert in medicine, seeks for drug information from fellow healthcare professionals and patients. In this digital era and period of artificial intelligence, information has become extremely reliable and helpful in providing evidence-based medicine practice. Documentation and information retrieval have become easier.

References Alois JF, Jonas E (1976) Skills in history-taking and physical examination. J Med Educ 51:410–415 Berman AC, Chutka DS (2016) Assessing effective physician-patient communication skills: “are you listening to me, doc?”. Korean J Med Educ 28:243–249. https://doi.org/10.3946/kjme. 2016.21 Consultation Skills for Pharmacy Practice (2014) Taking a patient centred approach. HSMO, St. Louis Finset A, Bosworth H, Butow P, Gulbrandsen P, Hulsman RL, Pieterse AH, Street R, Tschoetschel R, van Weert J (2020) Effective health communication—a key factor in fighting the COVID-19 pandemic. Patient Educ Couns 103(5):873–876. https://doi.org/10.1016/j.pec. 2020.03.027 Fitzgerald RJ (2009) Medication errors: the importance of an accurate drug history. Br J Clin Pharmacol 67(6):671–675. https://doi.org/10.1111/j.1365-2125.2009.03424.x Jalal Z, Cox A, Goel N, Vaitha N, King K, Ward J (2018) Communications skills in the pharmacy profession: a cross sectional survey of UK registered pharmacists and pharmacy educators. Pharmacy 6(4):132. https://doi.org/10.3390/pharmacy6040132

72

A. N. Nagappa and V. Naik

Kerr A, Kelleher C, Pawlikowska T, Strawbridge J (2021) How can pharmacists develop patientpharmacist communication skills? A realist synthesis. Patient Educ Couns 104(10):2467–2479 Odhayani A, Ratnapalan S (2011) Teaching communication skills. Can Fam Physician 57:1216– 1218 Ohm F, Vogel D, Sehner S, Wijnen-Meijer M, Harendza S (2013) Details acquired from medical history and patients' experience of empathy—two sides of the same coin. BMC Med Educ 13: 67. https://doi.org/10.1186/1472-6920-13-67 Sanii Y, Torkamandi H, Gholami K, Hadavand N, Javadi M (2016) Role of pharmacist counseling in pharmacotherapy quality improvement. J Res Pharm Pract 5(2):132–137. https://doi.org/10. 4103/2279-042X.179580 Schnipper JL, Kirwin JL, Cotugno MC, Wahlstrom SA, Brown BA, Tarvin E et al (2006) Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med 166:565–571 Schwartzman E, Chung EP, Sakharkar P, Law AV (2013) Instruction and assessment of student communication skills in US and Canadian pharmacy curricula. Curr Pharm Teach Learn 5:508– 517. https://doi.org/10.1016/j.cptl.2013.07.001 Svensberg K, Sporrong SK, Lupattelli A, Olsson E, Wallman A, Bjornsdottir I (2018) Nordic pharmacy students’ opinions of their patient communication skills training. Am J Pharm Educ 82:6208 van der Bles AM, van der Linden S, Freeman ALJ, Spiegelhalter DJ (2020) The effects of communicating uncertainty on public trust in facts and numbers. PNAS 117(14):7672–7683. https://doi.org/10.1073/pnas.1913678117

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies A. N. Nagappa and Vaishnavi Naik

Abstract

Pharmaceutical industry is a powerful lobby which always emphasizes on the consumption of its produce; however, the principles of therapeutics clearly state that all drugs are potentially toxic and need to be evaluated for risk-benefit analysis. If benefit overweighs the risk for a specific patient, then the patient can be prescribed. Medicines have lots of pharmacological actions along with therapeutic action. They are capable of interacting with all cells and tissues that they come in contact when administered. They can cause serious problems to the patient. It is the responsibility of the pharmacist to provide pharmaceutical care so that the patient is protected from such adverse drug reactions. Keywords

Pharmaceutical care · Prescription analysis · Patient counseling · Drug safety · Therapeutic drug monitoring

6.1

Pharmaceutical Care: WHO-FIP Model

In North America and Europe, 50 years ago, changes started appearing in the pharmacy field, which is described as reorientation from product-centric market to patient-centric market. The role of a pharmacist also metamorphosed from compounder/dispenser to patient counselor and healthcare provider. The pharmacist was

A. N. Nagappa Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India V. Naik (*) Department of Pharmacy Practice, Dayananda Sagar University, Bengaluru, Karnataka, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_6

73

74

A. N. Nagappa and V. Naik

previously primarily engaged in the supply of medicines to doctors, nurses, and patients. Pharmacist in his/her new role has become a healthcare service provider and information provider for patient care. Due to industrialization of pharmacy, availability of ready-to-use unit dosage form has killed the art of compounding of medicine. Compounding was abandoned soon which became outdated and obsolete. The skills of compounding like preparing tablets and antitussive triturates, filling the capsules with medicaments, dispensing the powders, and making ointments, mixtures, emulsions, syrups, suppositories, and pessary have remained a part of the history of pharmacy. Due to the educational systems which still teach the art of pharmacy, the latter has been kept alive in our thoughts and practice. Till today compounding and dispensing are taught across the world in many pharmacy schools and colleges. Although there is no utilization of this art in practice, it has become a part and parcel of the educational system in pharmacy. Fascinatingly compounding has renaissance in Europe and Australia and is practiced again in hospital pharmacies (Whitmarsh et al. 2010). Doctors demand for specialized dose, freshly prepared medicines, and medicines without preservatives or overage. In such circumstances, it is necessary to use the art of compounding. In hospitals, sometimes there will be bulk requirements of ointments, IV fluids, antitussive, and anti-diarrheal mixture for dispensing purposes. The practice of compounding will have a rebirth due to the limitations of manufacturers in ready-to-use fixed-dose combinations available in the market. As unit dose and fixed-dose forms are not meeting the individual patient’s requirement, in terms of dose, combinations, and excipients, there is a revival of compounding practices and implementation of new practices. Pharmacists are supposed to ensure drug therapy as appropriately as indicated by the doctors. After observing the laboratory reports and diagnostic results, doctors come to a decision regarding the conditions of the patient and accordingly write the prescription. The prescription may comprise lapses and omissions. A pharmacist should check the prescription meticulously for correctness of doses, duplication of medicines, duplication of therapeutic effects, and possibilities for drug-drug/food interactions. It is not to find a fault in prescription or doctor’s mistakes but to protect the patient from accidents due to wrong dose or duplication of medicine. The patient approaches the community pharmacist with the prescription for procuring medicines. Here the pharmacist has to observe and assess the patient and prescription and understand the intention of the doctor regarding the therapy prescribed to the patient. He/she should double-check the prescription by enquiring the patient about the disease he/she is suffering from. The pharmacist should be able to understand and communicate with the patient so that he/she gets confident to use the medicines. Patient counseling should reinforce the positive attitudes and good feeling with the hope of getting back to health. It is the genuine concern for the patient, when he/she suggests convenient dosing schedule. In case a prescription mentions that the medicine needs to be administered every 8 h (three times a day), in order to provide comfort for the patient, a pharmacist can advise him/her to take medicines without disturbing his/her night sleep. The timings for first dose may be fixed at 6 AM, second at 2 PM, and third at 10 PM. The

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

75

pharmacist should assume complete responsibility for medicine-related needs of the patient. The field of pharmacist comprises knowledge and skill, by which one makes unique contribution to the outcome of drug therapy (Anderson et al. 2009b). Pharmaceutical care was defined for the first time by Hepler and Strand in 1990 as follows: “The pharmaceutical care is the responsible provision of drug therapy for the purpose of achieving predetermined outcomes that improve the quality of life.” The concept of pharmaceutical care was adopted by the Federation of International Pharmacy (FIP), 1998, which emphasized on the commitment of a pharmacist for a definite outcome that improves and maintains patient’s quality of life. In the healthcare sector, many changes are happening like introduction of new medicines, appearance of new diseases, increased life expectancy, and increased number of geriatric patients exponentially. New innovations and new technologies are making the therapeutics highly competitive with better drugs, for example, the introduction of large number of new biotherapies with the help of cDNA and hybridoma technology. There are many challenges and issues about the manufacture and control of quality medicines of biotherapies in the industry. The rational use of medicines, especially biotherapies, poses the biggest challenge for the healthcare delivery as therapeutics become more complicated due to unpredictable adverse drug reaction and irrational use of drug therapy management (Anderson et al. 2009a). Transformation from a compounder to a clinical pharmacist was very important, and the change took time. Realizing the healthcare delivery scenario, the World Health Organization introduced the concept of seven-star pharmacist to guide and motivate the pharmacist to take up the new task of concerns in healthcare delivery. Pharmacists in new role are designated as caregiver, communicator, decision-maker, teacher, lifelong learner, leader, and therapy manager. FIP adopted the concept of seven-star pharmacist and added one more star emphasizing the role of pharmacist as a researcher. It is a benevolent task to change over the conventional image of a pharmacist from compounder and dispenser to a role of healthcare provider and drug information provider. It is easy to train the new pharmacists who are under growth phase than to educate the existing registered pharmacists. It is very difficult to update and change the practicing pharmacists to learn and provide clinical pharmacy services to the patients as per the changed scenario. The Government of India, in order to bridge the gap and update the present registered pharmacists, has introduced 3-year Bachelor of Pharmacy Operations (Practice) qualifications. In this program, the pharmacist is given training in pharmacy practice for 2 years. The registered pharmacist shall attend the classes on Saturdays and Sundays, and on weekdays they work in their jobs. In the third year, they continue with internship along with their jobs. Pharmaceutical care was a new intervention which had previously emerged in developing countries like India; pharmacists were happy with drug store management and dispensing activities. Pharmacists used to get paid on the basis of sales margins and discounts offered by wholesalers and drug manufacturers. Typically, pharmacists are confined to the conventional activities such as pharmacy management and logistical aspects of drug distribution, dispensing, and drug store

76

A. N. Nagappa and V. Naik

management. They are also involved in drug manufacturing and quality control activities of drug manufacture (Hepler and Strand 1990). The quality and safety of medicinal products in patients were a cause of concern; medicines were like a double-edged sword that had the potential to harm patients if not used rationally. In 2000, the FIP and the International Federation of Pharmaceutical Manufacturers and Associations jointly signed a pronouncement to ensure the quality and safety of medicinal products to protect patients. It set the agenda for pharmacy practice area, where the pharmacist is supposed to supervise the medications and doses for a patient as per their clinical needs. Pharmacists became the guardians of patients’ health and started counseling the patients in the matter of drugs, diseases, and lifestyles. Pharmacist is on the go for providing services like community health activities and advising the right way of storing and using medicines. They also stressed to the patients that the focus on healthcare is primary than treatments of disease. If they follow correct lifestyle and diet, the severity of the disease will be less, and dependency on medicines shall become least. This has a positive outcome in getting relief from the ADR and further consequences of drug-induced injuries. The health of the patient should be given importance than the treatment, and drug treatments should be avoided as far as possible. The strategy should be beyond disease and should try to achieve good health by adopting healthy lifestyle and balanced diet. It was soon realized that many microbes are acquiring resistance to antibiotics because of the indiscriminate use of antibiotics in disease treatment as well as use of antibiotics as hormones for growth promotion in the poultry and meat industries to get more meat weight in order to gain more profits. It is very dangerous as people who consume the meat are also consuming the antibiotics. Although it may benefit the meat industry, the damage caused to the environment and human health is enormous. Hence, we should be careful about hidden hormones and chemicals that may have entered the food chain and may damage the health of the individual and environment (Barber 2001).

6.2

Pharmaceutical Care: An Introduction

Globally, there have been significant changes in healthcare systems with respect to the quality and processes of drug usage. The transparency, efficacy, safety, and accountability of healthcare services are the primary requirements. The traditional role of the pharmacist involving in the preparation, dispensing, and selling of medications is no longer satisfactory. It signifies a paradigm shift of practice in pharmacy from drug product oriented to patient oriented. The new approach has been given the name “pharmaceutical care.” The most generally accepted definition of this new approach is the pharmaceutical care which is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient’s quality of life.

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

77

Fig. 6.1 Pharmaceutical care interventions

In adopting this definition in 1998, the International Pharmaceutical Federation (FIP) added one significant amendment: “Definite outcomes that improve or maintain a patient’s quality of life” (Penna 1990). Pharmaceutical care is a systematic process designed to identify and resolve drugrelated problems, and the process involves individualization of the pharmacotherapy, documentation, identification, and achieving economic, clinical, and humanistic outcomes while respecting the sovereignty and confidentiality of the patient by commitment of the pharmacist. In order to fulfill this obligation, the pharmacist has to assume many different functions. The concept of the seven-star pharmacist, introduced by the WHO and taken up by the FIP in 2000 in its policy statement on Good Pharmacy Education Practice, visualizes the pharmacist as a caregiver, communicator, decision-maker, teacher, researcher, lifelong learner, leader, and manager. Patients need a pharmacist’s services at the time of healthcare delivery. Pharmacotherapy is explicit for each patient. It includes individual drug therapy decisions, reaching an agreement between the patient and healthcare provider on the therapeutic outcome—cure of a disease. The elimination or reduction of a patient’s symptoms and arresting or slowing a disease process or symptoms are the prime objectives of patient-monitoring activities. For each individual patient’s drug treatment, the pharmacist develops a customized care plan in consultation with the patient. A systematic approach to patient care is illustrated in Fig. 6.1. Pharmacists are well matched to identify and resolve medication-related problems for transitional care, deliver medication education to patients, and update the patient families to make them manage medication therapy following discharge from hospitals. Such occurrences are fundamental to pharmaceutical care and are

78

A. N. Nagappa and V. Naik

embodied in the 2015 goals of the American Society of Health-System Pharmacists. Redesigned discharge processes that incorporate pharmacists to address transitional care lead to pharmacist-specific interventions such as medication reconciliation, patient counseling, and follow-up telephone calls (Hepler 2004). The pharmaceutical care model has clearly indicated the gap in healthcare and possibility of causalities due to the absence of teamwork of healthcare service providers. Pharmacists, being the expert in the matter of medicines, are in a unique position to think from a different angle than the physicians and nurses due to professional orientation and training. Healthcare services in developed countries are acceptably secure due to collaborative healthcare services by physicians, nurses, paramedical professionals, and pharmacists. The holistic approach and access of pharmacists, quality use of medicines, and evidence-based medicine cannot happen in the absence of contributions of paramedical staff (Lui et al. 2017). When a patient is experiencing or has the potential to experience an undesirable effect, which may be of psychological, physiological, economic, or social origin leading to drug-related problems (DRP), the pharmacist has to identify and prevent or resolve each of these listed below: 1. 2. 3. 4. 5. 6. 7. 8.

Need of pharmacotherapy, but not obtaining it Taking or receiving the wrong drug Taking or receiving too little of the correct drug Taking or receiving too much of the correct drug Experiencing an adverse drug reaction Experiencing a drug-drug and drug-food reaction Not taking or receiving the prescribed drug Taking or receiving a drug for which there is no valid medical indication

Pharmaceutical care is a patient-specific prospective, and requires pharmacist’s dedication towards it. Table 6.1 Summerize the services offered by the pharmacist before or at the time of drug therapy decision is more helpful to avoid further drugrelated problems. The necessary information about a patient’s clinical characteristics (age, sex, socioeconomic status, and biochemistry lab values), pharmacotherapy (allergy, recent or past pharmacotherapy), and disease process (severity, prognoses) will be significant. In the process of pharmaceutical care, pharmacists should attempt for the best interest of the patient while respecting the sovereignty and confidentiality of patients, which is essential for the delivery of pharmaceutical care. Documentation of care process should include information needed to make and take decisions, recording the decisions about individualized pharmacotherapy, and pharmacist’s actions on the outcome of the therapy. Database of the pharmaceutical care process consists of patient detail, drug, disease, drug of choice, and dose determinations. Route of administration, procedures and standards of patient monitoring, and patient outcomes in terms of efficacy, period of illness, and side effects are inherent properties of care process. Over the last few years, many studies have shown improvements in patient outcomes through the services by community pharmacists.

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

79

Table 6.1 New dimension of service offered by pharmacist Services Patient counseling Drug information service

Formulary development and management Medication error review Drug distribution overview Outcome monitoring and reporting Delivering clinical preventive services Surveillance and reporting of public health issues Information management and use of evidence

Focused outcomes Increasing medication adherence by improving the patient’s understanding of the therapy On the demand of the doctor or nurse or any other healthcare team member, information is given on the dosage, ADR, pharmacokinetics, etc. as a timely precise response Development of the hospital formulary with the help of other members of the healthcare team Prescription scrutiny to rule out the presence of errors in ensuring safe drug use Managing the distribution of drugs by acting as an important link between the stockist and consumers Observational role in which the pharmacist looks out for the economic, clinical, and psychosocial outcomes and analyzes the treatment and its alternatives Immunization education and service Pharmacovigilance and ADR monitoring Pharmacoeconomic analysis Development of standard treatment guidelines and essential drugs list (EDL) Providing information on the demand of nurses and physicians

In conditions like hypertension, diabetes, dyslipidemia, asthma, and coronary artery diseases, patients have shown gain in health. Pharmaceutical care in special-population geriatric and pediatric patients offers good opportunities for service. Nowadays, pharmaceutical care has become a foremost form of practice for thousands of pharmacists all over the world. However, for the patients and pharmacists in India, this concept remains unknown because it is not being practiced routinely and pharmacists, especially in community pharmacy, are not aware of the scope. It is important to emphasize the fact that pharmaceutical care is aimed to achieve rational and evidence-based pharmacotherapy, which is beneficial for patients and society. Independent pharmacies in developing nations can play an important role in reducing mortality and providing continuity of quality of care with improved life expectancy (Penna 1990; Hepler 2004). In India, pharmacists presently are having a trivial role in healthcare services. Patients’ therapy is managed by physicians with the help of nursing staff in an inefficient manner, thus leading to underutilization of services and knowledge of pharmacists. Healthcare delivery is presently not documented, and no accountability is in place. This may be the reason why doctors are not interested in a change of scenario. Physicians, who are unfamiliar with the importance of services of pharmacists, are declining to give the authority to pharmacists. Most of the doctors see pharmacists as less qualified and incompetent to provide pharmaceutical care. A

80

A. N. Nagappa and V. Naik

positive mutual relationship among healthcare professionals is beneficial for patients’ quality of health outcomes. India needs sustainable, high-quality human resources for healthcare delivery with a variety of skills and who are adequately distributed in all states, particularly in rural areas. Public health system has a shortage of medical and paramedical personnel. Government estimates indicate that 16% of hospitals are without a pharmacist. Hence, there is a need to develop a national human resource policy, which examines the creation and establishment of cadres of trained healthcare professionals who can provide leadership and direction to the healthcare sector to meet global standards. It should also make use of available pharmacists and train them in the pharmaceutical care area leading to sustainable human resource for healthcare. Now, let us examine the data which will show why we need pharmaceutical care in Indian population. India accounts for a substantial proportion of the global burden of diseases with 18% of mortality and 20% of disability-adjusted life years (DALYs). Of the estimated 10.3 million deaths that occurred in India in 2004, 5.2 million were due to chronic conditions. Overall, age-standardized mortality rates for chronic conditions were 769 and 602 per 100,000 men and women, respectively. Noncommunicable diseases (NCD) have evolved as major public health problems and accounted for 53% of all deaths in the age group of 30–59 years in 2000. It was projected that by 2015 these numbers may increase to 59% of the total deaths in India. People who are more prone to cardiovascular diseases (CVDs), especially coronary heart diseases (CHDs), are at risk to die at an early age than those people in high-income countries. As India’s population ages during the next 25 years, deaths caused by CVD are projected to reach four million in 2030 compared to 2.7 million in 2004. Tobacco is widely consumed and remains as the most important risk factor with 47% of men and 15% of women being regular consumers of tobacco. Even though NCDs are usually expected to occur in old age, their peak occurrence in India is a decade earlier than Western countries. Hence, the issue is not only the burden, but also its prematurity and the resulting socioeconomic consequences. India’s total expenditure on health was estimated to be 4.2% of GDP in 2009 of which public healthcare expenditure on health was estimated to be 1.10%. As per the WHO, out-of-pocket expenditure as a percentage of private expenditure on health in India was 74.4 in 2010. Out-of-pocket health expenditure has a great impact on the livelihood of patients. In 2004–2005, about 14% of rural and 12% of urban households spent more than 10% of their total expenditure on healthcare, leading to poverty. Thirty-nine million people (30.6 million in rural areas and 8.4 million in urban areas) fell into poverty as a result of out-of-pocket expenditure for healthcare needs in 2004–2005 and these are increasing day by day. Only about 10% of the Indian populations are covered by any form of social or voluntary health insurance, which is mainly offered through government schemes for selected employment groups in organized sector (e.g., State Employees Insurance). Private insurance companies account for 6.1% of health expenditures on insurance. Expenditure on drugs has been increasing with time and drug costs of drug constitute a greater proportion of out-of-pocket expenditures for people who are poor. Inefficient control of drug prices, regulation of pharmaceutical market

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

81

procurement, and distribution mechanisms exacerbate inequitable access to affordable good-quality drugs, which has caused chaos. Analysis of changes in drug prices has shown that the cost of the selected group of drugs rose by 40%, whereas the cost of essential drugs rose by 15% and the cost for those which are not on the controlled list and not price controlled rose by 33%. Inadequate protection of Financial risk and financial stakes that are associated with the cost of medical treatment (inpatient care, drugs, diagnostic test, and medical appliances) has worsened the poverty in Common man in India has become aware regarding the quality of healthcare services and has begun to demand for quality services. The current system is burdened and unable to sustain service expectations. Issues like inappropriate use of medicines and exploitation of ignorance and illiteracy of patients have been questioned in consumer forums. The apex professional bodies like the Medical Council of India are expected to act in the interest of patients rather than its own members. Doctors are needed to explain the treatment in detail to patients or patient party. The number of patients seen in a day by a physician is increasing to an all-time high, leaving little time to educate patients in the aspects of lifestyle modifications, use of modifications, use of medicines, and diseases. There are numerous opportunities for the pharmacist to assist physicians in hospitals as well as at retail pharmacies. Hence, pharmaceutical care has become the need of the hour in India and pharmacists can play a vital role in the healthcare system by providing their knowledge and skills in the usage of drugs and acting as providers of care to the needy patients. In India the concept of pharmaceutical care plan is not well developed as compared to developed countries like Australia, the United States, and Canada. In India, pharmacists were limited to drug dispensing and selling of drugs. In 2006, the World Health Organization (WHO) and the International Pharmaceutical Federation (FIP) developed guidelines on the process of delivering pharmaceutical care in a general practice environment. According to the American Society of Health System for Pharmacists (ASHP), “pharmaceutical care (PC) is the direct, responsible provision of medication-related care for the purpose of achieving a definite outcome that improves a patient’s quality of life.” Pharmaceutical care is a quality concept and working method for pharmacists. Here, the pharmacist cooperates with patients and other healthcare professionals in monitoring, designing, and implementing a therapeutic plan for the patient. Pharmaceutical care is provided for the direct benefit of the patient. Basically, it involves three major functions such as identification of potential and actual drug-related problem, resolving of the actual drug-related problem, and prevention of drug-related problem (National Health Accounts Cell 2009; Selvaraj and Karan 2009). Pharmaceutical care contributes to the optimization of outcomes from medicines and prevention of its inappropriateness and harms. It can be achieved by promotion of medication-related health literacy, participation and involvement of patients in their medications, and assignment and acceptation of responsibilities within the medication process. All together these factors improve the quality of life of patients and their families. Pharmaceutical care also contributes to increased use of medicines in a rational manner. The main goals of pharmaceutical care are to optimize the patient’s health-related quality of life (HRQOL) and to attain positive clinical

82

A. N. Nagappa and V. Naik

outcomes within realistic economic expenditure. Pharmaceutical care interventions that include monitoring and improving pharmacists’ knowledge and implementing pharmaceutical care philosophy and working method are represented in Fig. 6.1.

6.3

Elements of Pharmaceutical Care

There are subsequent elements of pharmaceutical care as given in Table 6.2.

Table 6.2 Elements of pharmaceutical care Element Medication-related aspects

Care

Outcomes

QOL

Responsibility

Explanation It includes the following: Actual provision of medications, decisions about the use of medication for an individual patient, decisions not to use medication therapy, judgment about medication selection, dosage, routes and methods of administrations, medication therapy mentoring, and provision of medication-related information and counseling to an individual patient • Pharmacist contributes to ensuring optimal outcomes from the use of medications • He/she is in a direct professional relationship with a patient where he/she provides care directly to the patient and for the benefit of the patient • He/she builds a direct, personal, caring assurance to the individual patient and acts as an ally for patient’s interests • He/she collaborates directly with other healthcare professionals and the patient in preparing, employing, and monitoring a therapeutic plan indeed to produce definite therapeutic consequences that improve the patient’s QOL. The outcomes sought are • Cure of the disease • Elimination or reduction of patient’s symptomology • Arresting or slowing of a disease process • Prevention of disease or symptomology • The pharmacist should determine the QOL of the patient and should try to improve it • He/she should be aware about various QOL tools available in the literature • In an informed way, the patients should be involved in ascertaining QOL objective for the therapies • The pharmacist should accept the responsibility of the patient to provide pharmaceutical care which involves both moral trustworthiness and accountability • He/she should develop professional relationship with the patient in which safety and Well-being of the patient should be entrusted • He/she must document care to provide as an accountable member of the healthcare team • The pharmacist is accountable for the patient’s outcomes, i.e., quality of care that resulted from the pharmacist’s decisions and actions

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

6.3.1

83

Functions of Pharmaceutical Care

As described by the ASHP (American Society of Health-System Pharmacists), the method for provision of pharmaceutical care should include the following functions:

6.3.1.1 Connection and Origination of Patient-Specific Information It is needed to prevent, detect, and resolve the patient’s medication-related problems and to make appropriate decisions for the therapy. The information to be collected may contain the following: 1. Demographics of the patient: It includes name, address, DOB, sex, occupation, religion, and social status. 2. Hospital-related/administrative information: It may include names of the physician/prescriber, pharmacy, bed/room no., consent forms, and patient identification no. 3. Medical information: It involves medical information of the patient such as prescribed and non-prescribed medications, medications used prior to administration, other health products used, medication regimen, compliance with therapy, medication allergies, concerns/question about therapy, assessment of understanding of therapy, and pertinent health beliefs. 4. Lifestyle information: It includes information on diet, social habits, exercise, sexual history, personality type, and daily activities. 5. Social/economic information: The information about financial/insurance plan, ethnic background, and living arrangement can be collected under this. Information can also be collected from the patient’s records and these records should be cross-checked and understood before making any decisions about the patient’s medication therapy. While collecting the information, the patient’s privacy and confidentiality should be maintained. The patient should be interviewed so as to maintain direct relationship, to understand the patient needs, to obtain medicationrelated data, and to augment other available information. 1. Determination of the presence of medication therapy problems: Medication therapy includes integration of medication, disease, laboratory results, and patient-specific information is done and conclusions. The problems related to the medication therapy as shown in Table 2 should be assessed. 2. Summarizing patient’s healthcare needs: Overall needs, desired outcomes, goals, and therapy plans for the patient should be considered here. 3. Specifying pharmacotherapeutic goals: The goals should reveal the integration of medication, disease, lab tests, patient-specific information with ethical clearance, and quality of life. 4. Designing a pharmacotherapeutic regimen: It should include integration of the factors as mentioned above with pharmacoeconomics principles. It should meet the terms of the health system’s medication use policy.

84

A. N. Nagappa and V. Naik

Table 6.3 Medication therapy problems 1. Improper drug dose, dosage form schedule, route/method of administration 2. Drugs with no therapeutic indication 3. Failure of medication adherence 4. Medical conditions for which there is no medication prescribed 5. Inappropriate drugs for a particular medical condition 6. Prescribing of drugs to which the patient is allergic 7. Actual and potential adverse drug events and drug interactions (drug-drug, drug-disease, drugnutrient, and drug-laboratory test) 8. Interference with medical therapy by social or recreational drug use 9. Failure to receive the full benefit of the therapy 10. Problems arising from economic impacts of therapy 11. Lack of understanding of the medication therapy by the patient l2. Therapeutic duplication

5. Designing a monitoring plan: For the evaluation of patient-specific goals and for the detection of real and potential adverse events, monitoring plan should be designed. Endpoints should be established for the assessment of completion of goals. 6. Development of a pharmacotherapeutic regimen and corresponding monitoring plan in collaboration with the patient and other health professionals: The regimen and plan should be systematic and logical and should represent a consensus among the pharmacist, patient, and prescriber. Regimen and plan should be documented to warrant that other healthcare professionals have this information. 7. Initiation of the pharmacotherapeutic regimen: The actions should fulfil the terms with the health system’s policies and procedures and match with regimen and plan. All actions should be documented. 8. Monitoring the effects of the pharmacotherapeutic regimen: It can be done by considering changes in the patient’s status, condition, medication, or non-medication therapy since monitoring plan has been developed. The evaluation should be done in terms of whether the pharmacotherapeutic goals were met before adjusting the regimen; cause of the failure to attain the goal should be found out. 9. Redesigning the pharmacotherapeutics regimen and monitoring plan: It should be done based on the patient’s outcomes and should be documented. SOAP Analysis and FARM Notes FARM note (findings, objective findings, assessment, and plan): The components of FARM and SOAP and the provision of pharmaceutical care plan for the pharmacist’s interventions in the form of two-way notes are summarized in Tables 6.3 and 6.4. Collecting the data from the patient and medical records, the pharmacist makes the FARM and SOAP, while subjective findings include the chief complaints of patient, objective findings, and previous allergy. Assessment is related to desired outcomes, endpoints, and drug-related

6

Pharmaceutical Care: WHO-FIP Model, Soap Analysis, and Illustrative Case Studies

85

Table 6.4 Components of FARM and SOAP notes Component Findings

FARM note F—Findings: Both subjective and objective data of patients

Desired outcomes Desired endpoints drugrelated problems

A—Assessment The pharmacist’s clinical judgment based on his/her finding— Thus, it is no better than the database (the finding): The assessment forms the basis for the intervention plan R—Resolutions/recommendation P—Plan M—Monitoring

Therapeutic selection Monitoring parameters Follow-up

SOAP note S—Subjective data of patients O—Objective data of patients

problems to find out whether the current therapy is relevant to standard therapy or not. Planning component covers the therapeutic selection, monitoring parameters (therapeutic and toxicity), patient education, follow-up, and documentation of patient profile form (Podder et al. 2021; Toklu and Hussain 2013). Benefits of Pharmaceutical Care The following are the benefits of PC: • • • • • •

It leads to decreased medication errors. It builds better relationship between patient and pharmacist. It improves compliance and adherence of the patient with the therapy. It may provide better management of chronic diseases. It may prevent adverse events in a treatment because of drug-drug interactions. It improves the knowledge, understanding, and outcomes of the patient about the therapy. • It improves the QOL of the patient (and many research studies have proved it). All these benefits can also be obtained in a hospital and community setup.

6.4

Conclusion

Pharmacists are experts in medicine and are easily accessible to patients, and hence it is natural for a patient to approach the pharmacist for immediate relief from sufferings with decide-and-ask questions to the pharmacist to guide the patient. Pharmacists, after receiving the prescription, check the prescription analysis and open a dialogue with patients; after hearing, the pharmacist is supposed to prepare a customized pharmaceutical care and administer it to the patient and is advised to contact back the pharmacist in case the situation of the patient worsens. Otherwise, the patient is called for a visit in order to check the outcomes in patients. If the patient is not showing any improvement then the pharmacist attempts to find out the cause for failure of treatment. The patients are referred to doctors or nurses. The primary

86

A. N. Nagappa and V. Naik

role of a pharmacist along with dispensing of medicine includes optimization of the therapeutic outcomes.

References Anderson C, Bates I, Beck D, Brock TP, Futter B, Mercer H, Rouse M, Whitmarsh S, Wuliji T, Yonemura A (2009a) The WHO UNESCO FIP pharmacy education taskforce. Hum Resour Health 7:45 Anderson C, Bates I, Bruno A, Futter B, Rouse M, Whitmarsh S (2009b) Pharmacy education. In: Wuliji T (ed) FIP global pharmacy workforce report. International Pharmaceutical Federation, The Hague. http://www.fip.org/healthcare_workforce. Accessed 24 Aug 2010 Barber N (2001) Pharmaceutical care and medicines management—is there a difference? Pharm World Sci 23(6):210–211 Hepler CD (2004) Clinical pharmacy, pharmaceutical care, and the quality of drug therapy. Pharmacotherapy 24(11):1491–1498. https://doi.org/10.1592/phco.24.16.1491.50950 Hepler CD, Strand LM (1990) Opportunities and responsibilities in pharmaceutical care. Am J Hosp Pharm 47(3):533–543 Lui E, Ha R, Truong C (2017) Applying the pharmaceutical care model to assess pharmacist services in a primary care setting. Can Pharm J 150(2):90–93. https://doi.org/10.1177/ 1715163517690538 National Health Accounts Cell (2009) National Health Accounts-India (2004–05)—with provisional estimates from 2005–06 to 2008–09. Ministry of Health and Family Welfare, New Delhi Penna RP (1990) Pharmaceutical care: pharmacy's mission for the 1990s. Am J Hosp Pharm 47(3): 543–549 Podder V, Lew V, Ghassemzadeh S (2021) SOAP notes. StatPearls Publishing, Treasure Island Selvaraj S, Karan A (2009) Deepening health insecurity in India: evidence from national sample surveys since 1980s. Econ Pol Wkly 44:55–60 Toklu HZ, Hussain A (2013) The changing face of pharmacy practice and the need for a new model of pharmacy education. J Young Pharm 5(2):38–40. https://doi.org/10.1016/j.jyp.2012.09.001 Whitmarsh S, Futter B, Rouse M, Bates I, Anderson C (2010) A case study in terminology: the FIP pharmacy education taskforce. Am J Pharm Educ 74(7):134. https://doi.org/10.5688/aj7407134

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Participation, Drug-Drug Interaction and Drug-Food Interaction, Prescription Analysis, PTC Activities, Formulary Management, and TDM Services A. N. Nagappa and Jovita Kanoujia

Abstract

The role of pharmacist in hospital can be divided by the activities carried out by the pharmacist. The clinical pharmacist is team member of doctors and nurses contributing to clinical decision-making. The hospital pharmacist is responsible for stocking, distribution, and management of pharmacy-related services to the hospital. Hospital pharmacy is a core member of drugs and therapeutic committee deciding inventory of medicine and surgical items for the hospital. The clinical pharmacists are specialized in patients’ counseling and engaged in patients’ education and act like a link between the patient and therapeutic. Hospital pharmacists are specialized in compounding skills by which they prepare extempore formulations and bulk formulations like normal saline and ointments to be dispensed to the inpatients and outpatients against the prescription of the doctor of the hospital. Keywords

Drug and poison information services · Ward rounds · Pharmacy and therapeutic committee · Drug information services

A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_7

87

88

7.1

A. N. Nagappa and J. Kanoujia

Clinical Pharmacy Services: Drug and Poison Information

Drug information is as important as drug itself; if you have the drug and do not have the information about the drug, it is not possible to use that drug for the benefit of the patient in the treatment of disease. Due to massive effort of scientist healthcare provider, there is enormous information available in the public domain. The data about drugs are continuously added, and the database is very large. Without proper background about health information and skills, it is very difficult to assess and search the precise information from databases. The request for information arises while treating the patients, on a specific issue or topic. Making timely availability of the relevant information/data in a specific format can help the doctors to take the appropriate decision which can save the life of a patient and improve the patient condition. This is the importance of drug information. Drug/poison information services are institutionalized, and specially trained pharmacy personnel heads a drug/poison information center. The organization of drug/poison information center and its working plays a crucial role in practicing evidence-based medicine and rational use of drugs as shown in Fig. 7.1 (Raehl et al. 1998; Christensen and Farris 2006). The first Drug Information Centre (DIC) was started in University of Kentucky, USA, in 1960. The Drug Information Centre becomes very popular, and presently 80% of the corporate and teaching hospitals have Drug Information Centre in developed countries. Drug Information Centre is headed by drug information scientist with pharmacy background. In India, Drug Information Centre was first started in the Department of Pharmacology at Christian Medical College, Vellore, Tamil Nadu. Recently, most of the hospitals are attached to Doctor of Pharmacy (Pharm D) program of a college with established drug information center in the Department of Pharmacy Practice. Drug information services became important due to increase Fig. 7.1 Workflow of DIC using evidence-based medicine approach

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

89

in number of drugs used in treatment and introduction of new drugs. The new drugs when they are introduced generally are not known to the doctors; due to this reason, doctors always depend upon the medical representative for information. Medical representative cannot be trusted as their primary interest is to meet the target of volumes on sales fixed by the marketing department. There is a huge expansion of literature about medicines. It becomes very difficult to keep an update and use medicines in a rational manner. An independent in-house drug information center is preferred over the information provided by the drug manufacturer (Grossman et al. 2020). Relaying on formulary and pharmacopeia is not sufficient to provide quality information to the healthcare provider and patient. The objective of DIC is to provide latest drug information to doctors, nurses, and pharmacist on specific issues related to the use of drugs in a particular patient. Sometimes the Drug Information Centre is asked for information by the government in order to implement a policy about a new drug, for which an application for license is pending to market the product. The DIC has to search the resources using their skills and provide unbiased information to the regulators. DIC provide a great help in the preparation of hospital formularies for using in wards for the healthcare professional in day-to-day treatments. The drug information services are engaged in advocacy regarding improving the patient compliance and provide information for the patients about informed selfmedication. The difference between informed self-medication and self-medication is when registered pharmacist initiates minor ailment treatments with OTC medication. In self-medication patient, he/she directs the pharmacist to dispense medicines. It is important to discourage the self-medication by patients as this may land the patient into serious consequences. The DIC educate the patient regarding the proper way to use medicines. Drug Information Centre is engaged in educating the healthcare provider and updating their knowledge. Drug Information Centre also engaged in continuing education programs about latest developments about drug, devices, and guidelines of new drugs use. The Drug Information Centre engages interns and students in such activities of Drug Information Centre and trains the young pharmacist. It is also important for the DIC to develop educational activities focused on patients attending community pharmacies regarding rational use of drugs. Drug Information Centre shall be preparing and distributing the concise information to be used by the healthcare professionals in the form of a drug bulletins. They can also engage in research activities like data mining and data use along with development of digital repositories and patient registries (Stoukides 1993).

7.2

Sources of Information for Drug Information Centre

The advent of big data and cloud technologies has made the storage and retrieval of information simple, cost-effective, and easy. Drug information is getting accumulated in a very big manner which not only continues but also is diverse. For example, if we look at process of drug research, there are various multidisciplinary teams all across the world that are conducting research and publishing in public

90

A. N. Nagappa and J. Kanoujia

domain. The journals are engaged in publishing the research findings. Information from published research is meant for updating the therapeutic process. If the data need to be protected by intellectual properties, the findings should be registered as a patent with patent office before publishing. The published patent has a clear information about the drug, with its background, and it declares the knowledge added by the new patent that is covered in the patent. One who wants to further research can update by going through the patent which is available free of cost in the public domain. There are some agencies who share scientific information in the public domain free of cost to encourage research and development such as PubMed central. There are also specialized database services free and paid subscriptions, for example, Medscape and Cochrane collaboration. Among paid subscriptions for drug information are Laxicom and Micromedex (Chauhan et al. 2013). The sources of information available are classified as primary, secondary, tertiary, and miscellaneous sources. Primary source of information is available through published articles in scientific journals and periodicals. The PhD theses and conference proceeding are also considered as primary source of information. One of the advantages of the primary source is it provides the latest information about drugs. The secondary source of information has been evaluated by a second party other than the researcher. The secondary source of information is subjected to critical review which gets modified and also formatted, for example, literature including review articles, systematic reviews, meta-analyses, and reference works. Secondary literature also includes indexing and abstracting services. LexisNexis is a corporation founded in 1970 involved in regulatory, legal, and risk management services. MEDLINE (Medical Literature Analysis and Retrieval System Online, or MEDLARS Online) is a bibliographic database containing biomedical and life sciences information. It provides bibliographic information from academic journals related to veterinary medicine, nursing, medicine, pharmacy, dentistry, and healthcare. Lexicomp, a database of Kluwer publishing company, provides customized, clear, concise, point-of-care drug information. It covers dosing information, drug administration, warnings and precautions, as well as clinical content, such as clinical practice guidelines. It has also updated information about IV compatibility from Trissel’s 2 Clinical Pharmaceutics Database and other tools. Micromedex is an online evidence-based database that includes “in-line” referenced information about diseases, toxicology, drugs, acute care, and alternative medicine for healthcare professionals. It helps them to make decision on clinical diagnosis and treatments. Tertiary literature references are condensed works based on primary and secondary literature, such as textbooks, encyclopedia articles, and guidebooks or handbooks. The tertiary literature provides an overview of key research findings and an introduction to principles and practices. These are the types of references most commonly used in both the pharmacy environment and classroom, for example, all pharmacopeias and formularies such as BP, USP, IP, BNF, NFI, etc. along with encyclopedia, dictionary, guides, and textbooks.

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

91

Miscellaneous information resources for drug information center are from the public and hospital bulletins, local drug laws, hospital formularies, national formularies, Internet, and phone calls to manufacturer, government, and nongovernment organizations (Hansen et al. 2004; Drug Information Center Karnataka State Pharmacy Council 2007).

7.3

Skills of Drug Information Services

Drug information services require specialized skills of speculating, what is the purpose of inquiry. A check into the details about who has asked the information and what is the purpose of asking for the information, how the information is going to be used must be done in drug information center. A brief workout is a must for drug information scientist before he/she prepare the dossier of information. The protocols for providing the drug information are modified by systemic seven-stepwise approach given in Table 7.1.

7.4

Seven Steps for Providing Drug Information Service

7.4.1

Evaluation of Drug Literature

The drug literature is available in primary, secondary, and tertiary resources. The drug information scientist should always keep himself abreast with the latest development. The information gathered worldwide gets accumulated in various types as mentioned above. The person in charge should practice information by continuously exposing him/her by reading, writing, and publishing information through active involvement. Among the skills, knowledge of drug literature and critical analysis are essential for understanding and providing the information to the healthcare providers and P&HC. Healthcare providers who are well versed with medical knowledge prefer the communication in a professional style. P&HC who are not well versed with a medical terminology and knowledge wishes the information be simple and understandable. It is important for the drug information scientist to provide high quality of information without creating any confusion. He/she should be able to identify and distinguish the quality of data, so that he/she can ignore substandard data. It is also important to realize the limitations of data available, and information should never be inflated and should have logic for the basis of available data. The information should be supported with appropriate references for cross checking openly the quality of information provided (Davidson 2015; Shields et al. 2011). Drug information inquiries usually arise in order to resolve a clinical issue or to get lead in clinical treatment. In a hospital, DIC is located in the Department of Clinical Pharmacology. The information inquiries should answered after finding out the information from a genuine resource, and one should never relay to a guess work. The information given is going to affect the treatment process and outcome. It is also important to maintain the privacy of the patient and should never disclose the patient

Step 2 Purpose of information inquiry

Where he/she heard about the drug

Whether he/she is taking the medicine. Why?

Is he/she a caregiver/ wishes to use this drug

Step 1 Details of information seeker

Healthcare professional/ P&HC

Educational background

Contact details, phone, email

–

–

–

–

Putting the information together to form a ultimate question

Step 4 Strategies should be framed with the typical algorithm for the source of information into primary, secondary, and tertiary source –

Step 3 Determination and classification of question

Table 7.1 General guidelines while responding to drug information inquiry

–

–

Quality reply should be given which takes time and insight

Step 5 Evaluate analysis and synthesis

–

Outline should be established to help for the formulation of response as per the question; it should be divided into introduction, body, and conclusion –

Step 6 The provision of formulation of information and response

Documentation of service provided for further training and improvement of quality –

Get the feedback from the information seeker whether drug information provided had met his/her request completely

Step 7 Follow-up and documentation

92 A. N. Nagappa and J. Kanoujia

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

93

related-information to a third party except when a court orders for judicial purpose. It is very important to understand that never to breach patient and healthcare provider relationship. While transiting with the patient one should be with the positive body language, otherwise it can create a suspicion or doubt in the patient mind. DIC should act as a bridge between patient and healthcare provider. Information may be withheld or denied in case DIC has enough reasons to believe; inquirer intends to misuse or abuse information provided. The guidelines for responding to drug information inquiry should be followed as given in Table 7.1 (Tefera et al. 2019). It is also important to provide the information in such a manner that the inquirer understands the information to some extent and that inquirer is able to use information for the benefits of the patient. It is very important to understand the background of the inquirer before preparing the response of the inquiry. It is equally important to reveal the source of information searched and found. DIC should not unnecessarily delay in giving a response and should inform the inquirer approximate waiting time, for providing the response. At the exit point, DIC person should ascertain whether the inquirer got the proper answer for the question he/she raised (Ali et al. 2013).

7.5

Organization of the Drug Information Center

DIC are usually located in the premises of the hospital. They may also be located in the community along the community pharmacist or may be in the office of professional organizations. DIC specialized in providing critical information about therapy, drug dossier, pharmacovigilance data, formulary data, and pharmacogenomics. It should conduct continuous education program for the hospital staff about new drugs, new therapies, and other progress in research about hospital-related issues. Its credibility and professional status depend upon its commitment to provide unbiased information to healthcare provider and P&HC. They must engage on continuous basis to enhance the skills of healthcare professionals to access and handle the drug information by activities like workshops and training programs (Beena and Padma 2005). The staff of a DIC is usually designated as drug information scientist who has degree in pharmacy and diploma in information technology. He/she is having a thorough knowledge about medicine, pharmacology of drugs, and pathophysiology of diseases. They are assisted by interns, students, and pharmacy technician. The other staff assists the drug information scientist in conducting literature search, retrieval of data along with explicit information given in RCT, systematic reviews, and meta-analysis. The other supporting staff of DIC includes personnel with library science and computer knowledge. DIC should have specific hours of regular operations; however 24
7 services are preferable. DIC should be equipped with adequate online subscription of databases. It should also have infrastructure of communication like telephone lines, fax machine, and advanced library resource. In order to keep themselves updated with recent developments, they should publish newsletters or bulletins and circulate them among the healthcare providers. Drug information bulletins are the periodicals published by drug information center

94

A. N. Nagappa and J. Kanoujia

(Alomi et al. 2018). These are the public face of the DIC. The challenge of bulletin is to make it an interesting and important publication for the healthcare providers in the hospital. The regular columns in the bulletins should contain columns about latest development in therapy, new drugs, new indication of an existing drugs, and articles written by expert healthcare professional from the hospital. Bulletins are the media to communicate the professional information and also conduct a teaching program for the hospitals staff. The bulletins also publish inter-departmental collaboration which is displayed in notice board. Bulletins are distributed in meetings of hospitals staff. There may be an update information alert of the drug interaction and adverse drug reactions. Although primarily DIC is in charge of editorial compilations, contributions should also be invited by other hospital service centers. The materials published should be educative and informative with relevance to the hospital work. The soft copies of webinars and short videos can be included in the electronic mode of the bulletins (Ghaibi and Ipema 2015).

7.6

Poison Center

Accessibility and exposure to poison in day-to-day life may be accidental or intentional. It is very important to save the life and minimize the damage to life that is caused by the poison or any therapeutic agent or household items. Sometimes the therapeutic agents may become poisonous. Previously all therapeutic drugs were to be labeled as poison for alerting the public and healthcare professional to be cautious. Nowadays there are no such labeling instructions to the public. Although therapeutic drugs help the patient in recovering of diseases, in case if the drug concentration in the blood remains above toxic dose, medicine becomes poisonous to the person. On the other hand, drug concentration remains below the effective dose; medicine may fail to produce good effect. It is important to see that the drug concentration never goes above the MTC (minimum toxic concentration) but remains within therapeutic window to ensure drug action. There are some drug actions which are independent of concentration, e.g., allergic drug reactions. Providing timely poison information can be lifesaving. Hence poison information center should be more alert to provide the poison information (Lall and Peshin 1997). The first poison information center was opened in North America as early as 1950. The international program on drug safety and drug levels is enforced strictly by the laws. The poisons stock and sale were regulated in order to avoid suicides. The World Health Organizations (WHO) is the pioneers in promoting international program on chemical safety and health. Poison information was established in 1980 to provide guidelines on the use of risk assessment to human health and environment along with safety guidelines. Further it has also published information regarding management of emergency in poisoning cases. The poison information center aims on the prevention and treatment of poisoning in collaboration with World Federation of Associations of Clinical Toxicology Centers and Poison Control Centers. European commission is working on similar lines of IPSE. Both agencies work in

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

95

collaborations to established and manage poison information centers by sharing and exchange of information (Churi et al. 2013). Poison information center provides the services based on the regulation of the country. For example, the provision of service regarding poison and managing with poisoning cases is an active help. Due to lack of information, many patients and health consumers faced casualties of poisoning. The aim of establishing poison control center is to provide timely quality information and the management of emergencies due to poisoning. It also helps in prevention of poisoning episodes. Poison control center (PCC) is having a pharmacist who helps in documenting the cases and treatment given to the victims of poisoning. PCC is having toxicologist on board specializing in toxicology. The other staff of PCC is a librarian with computer knowledge. PCC is specialized unit providing information on poisoning to the whole of community. Activities of PCC are providing toxicological information and advice management of posing cases, establishment of analytical services laboratory, toxicovigilance, research, education, and training in the prevention and treatment of poisoning. Center should be actively involved in development, implementation, and evaluation of various measures for prevention and also take up the extended responsibility of toxicovigilance. The contingency plans for poison treatment and problems of drug abuse should be prepared and kept ready to share the information by telephone on emergency 24X7 models (Ellington et al. 2008). The PCC also should provide educational programs to alert the public on how to react poisoning incident. Other responsibility of poison control center is to build a database on poisoning episode and perform observational research. The staff should be trained in handling hazardous material spillage. They should also keep a track on environmental toxicology. Toxicovigilance involves identification and evaluation of toxic risk and evaluates the major step taken to reduce or eliminate the risk (Descotes and Testud 2005).

7.7

Ward Round Participation

Ward round is a visit made by healthcare team to the bedside of the inpatients to review and follow up the progress in health condition. This practice has resolved the issue of time management for the doctors and other health providers; each ward is serviced by nursing stations where nursing professional provides nursing services to inpatients. The patients who are admitted in the hospital mostly have a serious condition and need bed rest and continued medical care. It is not possible for doctor to spend all the time with a single patient or in a single ward. However it is also not practical to provide 100% vigilance on individual patients by doctor alone. Senior doctors also have the responsibility to teach clinical skills to interns and postgraduate students. The ward rounds fulfill all these requirements. The team of doctor, nurse, and pharmacist go forward rounds and observe the inpatients and also the cases reports maintained in the wards near the impatiens bed. Doctors go through the case reports and summarize the inpatient conditions. They also look into ongoing

96

A. N. Nagappa and J. Kanoujia

treatment and observe whether the treatment is improving or deteriorating the patient condition. Critical observation prompts doctors to make a strategic change in the treatment (O’Hare 2008). During treatment doctor may request nurses and pharmacist to provide him/her with patient history and about medicines that are used by inpatients. The ward round is most successful approach for providing all types of treatments to patients in limited resources. The role of clinical pharmacist in ward round involves finding out whether the drugs prescribed and administered have an indication in the patient. Sometimes due to lack of concentration, a doctor might have prescribed a medicine without an indication. In such cases, the pharmacist should alert the doctor and nurse regarding the using of a drug without an indication. It can also happen so a doctor might have forgotten to write a prescription where there is an indication. A pharmacist should sharpen his/her clinical knowledge and discuss the matters with doctors and nurses to comprehend the motive for prescribing. There is a possibility of medication error due to inappropriate doses, duplication of medicine, or prescribing similar acting drug. For example, in hematology, for anticoagulant action, administration of NSAIDS may cause the over dosage of warfarin leading to serious bleeding and hemorrhage. Clinical pharmacist should calculate the dose of antiplatelet drug by calculating the INR values and recommends the does adjustment. In a structured ward round, healthcare team engaged in patient care meet frequently to discuss the treatment strategy. This provides a platform where communication happens and feedbacks are noticed and considered. During ward rounds, healthcare team is able to understand the patient needs and problems. The ward rounds should be patient centric and be the integral activity of patient care. The team of ward rounds should be multi-disciplinary and lead by senior doctors who gets updated patient information from patients and fellow team members who shall provide information according to their professional commitments. For example, senior nurse updates the team on present status and conducts safety checks on patients and also helps the patients in communicating their requirements. Similarly a clinical pharmacist reviews the medications and other matters pertaining to medicines, for example, adverse drug reaction and drug toxicity. Clinical pharmacist also provides discharge medication counseling to the patients. The ward rounds are classified depending on the purpose. For example, in teaching hospital, ward round aims at improving the clinical skills of interns, registrars, and specialist. Here a senior doctor along with junior doctor moves from bed to bed demonstrating diagnosis and treatment. In prior to ward rounds, interns and the junior doctors are asked to make therapeutic notes about the newly admitted patients and study case history to become acquainted with patient condition. In traditional ward rounds, all doctors attending the patient meet and discuss regarding the treatment process and review the patient’s progress. During ward rounds, medical team should visits the inpatients to review their conditions and plans the future course of treatment strategy. The objective of ward rounds is to gain an improved understating of patients’ clinical status and progress in their conditions and review investigation matching

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

97

with therapeutic goals. Another important objective of ward rounds is to summarize the patient condition and drug therapy-related factors like pharmacokinetics, bioavailability, cost of the drugs, drug-drug interaction, and drug-food interaction along with adverse drug reactions. The optimization of drug therapy management can happen during ward rounds, wherein a pharmacist may advocate and influence the doctors in drug therapy sections. He/she can be useful in the implementation of knowledge in drug monitoring and follow-up of drug therapy. Clinical pharmacist with his background is able to identify unusual drug orders or doses and alerts the doctors who can change prescription leading to reduced cost of the treatment. During ward rounds, healthcare team learns about comorbidities of the patient, issues with medication compliance, or use of alternative medicine the patient is using. Timely detection and mitigation of adverse drug reaction and drug-drug/food interactions is possible during ward rounds. Clinical pharmacist can monitor the patients who are at a greater risk of developing a serious adverse drug reaction. He/she can also check the prescribed medicines having high risks of inducing adverse drug reactions. Further the clinical pharmacist can engage with patients and learns about the patient’s allergic history. The patient on multiple medicines (polypharmacy), the assessment of prescription and drugdrug/drug-food interactions is an important action to avoid any type of adverse effect (Perversi et al. 2018).

7.8

Clinical Pharmacist Leads Ward Rounds

Although multidisciplinary ward rounds are routinely engaged in hospitals, a clinical pharmacist-led ward rounds are to be the foresight in the future. The major drawback of multidisciplinary ward round is focused on diagnosis and treatment. There is no much scope for the clinical pharmacist to intervene in the ongoing therapy. The clinical pharmacist being a member of multidisciplinary team many times is not involved properly as the focus of the team is on diagnosis and treatment. There are many lapses leading to medication errors that can be observed in wards which are ignored. The clinical pharmacist goes for independent ward round with team of interns looking for issues related to medicine. For example, calculation of doses which are administered to inpatients, indication and contraindication checking, drug interaction, and food interaction in a systematic manner can be carried out to identify many issues which need to be corrected. Correction of the errors could lead to improved quality of inpatient life. The patients/nurses might have been using medicines in a wrong manner which needs to be corrected after the identification. Hence in the future, the head of the clinical pharmacist should lead the independent ward rounds to check the rational use of the medicines avoiding errors while using the medications (Miller et al. 2011).

98

7.9

A. N. Nagappa and J. Kanoujia

Drug-Drug Interaction and Drug-Food Interaction

Drugs are used to mitigate symptom of disease along with curing the disease. Many drugs are capable of providing immediate relief from symptom of disease, and they may not be acting on the cause of the disease. For example, if there is an infection and inflammation due to infection, the treatment to relief from inflammation should not be the primary goal of treatment. Treatments of infection should be the primary goal and prioritizing of infection and inflammation should be on symptomatic basis. The control over infection shall also bring down the severity of inflammation. If the patient is known to have hypertension and diabetes, then the patient needs to take medicines for management of diabetes and hypertensions. The result of treatment should contain anti-inflammatory drugs along with medicines for hypertension and diabetes. One should not forget the risk of renal damage by the drugs used for treatment of hypertension and diabetes simultaneously. Patients are recommended large number of drugs for each indication leading to polypharmacy. The patients who administered with large numbers of drugs for a longer period of times in different indications the chances of drug-induced organ damages is more (Dirin et al. 2014). Drug-drug interaction is defined as when a pharmacological activity of a drug is altered by the simultaneously use of another drug or by presence of some other substance. For example, the activity of warfarin gets altered when aspirin is administered simultaneously and administration of tetracycline along with milk/ antacids. In the case of warfarin and aspirin, there is a danger of bleeding and hemorrhage. Tetracycline loses its antibacterial activity in the presence of milk/ antacid due to chelation of calcium ions of milk/antacid. Here the warfarin and the tetracycline are called object drug, and aspirin and milk are referred as precipitant. Drug interactions can be classified as drug-drug interactions, drug-food interactions, chemical and drug interaction, drug and diagnostic interactions, and drug disease interactions (Shafiekhani et al. 2019). The examples are given in Table 7.2. The net effect of drug interactions is either increase or decrease in compare to the effect of object drug or it may also lead to appearance of new adverse reaction or enhance adverse effect. Drug interaction sometimes is beneficial. For example, penicillin G is administered with clavulanic acid; the bioavailability and duration of action of penicillin G are enhanced. The clavulanic acid gets excreted in the urine instead of penicillin G; however in most of the cases, the drug interactions are undesirable sometimes leading to serious casualty (Yu et al. 2021). Table 7.2 Types of drug interactions

S. no. 1 2 3 4 5

Types of drug interactions Drug-drug interactions Drug-food interactions Chemical drug interaction Drug diagnostic interactions Drug disease interactions

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

99

If the patient gets treatment from different doctors for different disease, multiple prescriptions lead to polypharmacy. The drug interactions happen due to polypharmacy treatment with many drugs together. In many instances, each drug will be manifesting multiple pharmacological effects that may be the reason for drug interactions. Multiple disease and illness in a patient predispose him/her to take multiple drugs together. If the patients is not agreeing with the therapy and using the drug in irrational manner, it may lead to poor compliance leading to drug interactions. Due to aging, the patient may have altered physiological conditions leading to drug interactions. For example, many patients lose the ability to metabolize the drug like young adults leading to drug toxicity. The drug interaction may also happen due to physiochemical properties of the drug commonly known as drugrelated factors. The mechanisms of drug interaction are classified into three categories, viz., pharmaceutical interaction, pharmacokinetic interaction, and pharmacodynamic interaction. Pharmaceutical interaction happens due to physiochemical properties of drugs, for example, while mixing two or three medicines before intravenous infusion. Ampicillin, chlorpromazine, and phenobarbital may interact with the dextran IB solutions when mixed which can cause degradation leading to precipitation or inactivation of active principles. Pharmacokinetic interactions are those which affect absorption, distribution, metabolism, and excretion of the object drug by the precipitant drug, resulting in altered plasma concentration of the object drug. In absorption drug interaction, the object drug is either absorbed fast or slow and may have reduced or enhanced drug absorption (Palleria et al. 2013). The major mechanism of absorption-based interaction with examples is given in Table 7.3.

7.10

Prescription Analysis

Prescription analysis aims at identifying unethical promotion of drugs which is a serious problem. It is an approach to gather relevant and actual information from the stakeholders, like patients (Fig. 7.2). It also gives an insight on the state of affairs of irrational use of drugs. It helps in checking unethical alliances of hospitals and doctors with diagnostic centers. It provides an opportunity to assess the confirmation of the treatment with existing clinical guidelines. It also helps to get an insight into the pattern of drug usage and adherence to therapy by the patients. One can also estimate the cost of treatment and also learn about perception of the patients (Pandey et al. 2010). Prescriptions are the decision of the doctors following the diagnosis, and estimating the risk-benefit analysis of each drug on patient health is recommended for the patients. If the patient is admitted in the hospital, the nurses and clinical pharmacist can do the risk-benefit analysis. However, if the patient is an outpatient or on ambulatory care, the community pharmacist has to analyze the content of the prescription for a patient. Prescription error can arise from varieties of lapses at every step of drug purchase and use by the patient. First of all doctors who prescribe medicines to patients do not have comprehensive information about the medicines.

100

A. N. Nagappa and J. Kanoujia

Table 7.3 Absorption-based drug interaction S. no 1

Mechanisms Complexation and adsorption

Object drug Ciprofloxacin, penicillamine

Precipitant drugs Antacids, food, and mineral supplements containing Al, mg, Fe, Zn, and ca ions

2

Alteration in GI pH

Sulfonamides, aspirin ferrous sulfate

Antacids, sodium bicarbonate, calcium carbonate

3

Alteration in gut motility

Metoclopramide

4

Inhibition of GI enzymes.

5

Alteration of GI microflora

Aspirin, diazepam, levodopa, mexiletine Levodopa, lithium carbonate, mexiletine Digoxin

6

Malabsorption syndrome

Vitamin A, B12,digoxin

Neomycin

Influence on object drug Formation of poorly soluble and un-absorbable complex with such heavy metal ions Enhanced dissolution and absorption rate and decreased dissolution and hence absorption Rapid gastric emptying, increased rate of absorption

Anticholinergics

Delayed gastric emptying, decreased rate of absorption

Antibiotics

Increased bioavailability due to destruction of bacterial flora that inactivates digoxin in lower intestine Inhibition due to malabsorption

Fig. 7.2 Schematic diagram of patient and health consumes with stakeholders

They are supposed to interact with clinical community or hospital pharmacist. However instead of this doctor prefers to prescribe the medicines based on the knowledge acquired by the pharmaceutical marketing team. Using the information from the manufacturer should be avoided by the doctors. Manufacturers are accused of overdoing promotional activity leading to alteration of judgment of a doctor and writing irrational prescription. If the system does not check the content of a prescription, then there can be widespread abuse of

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

101

prescription medicines leading to many drug-induced injuries. The government and regulators being aware of this problem have pressurized doctors not to have any liaison with the pharmaceutical industries. The errors in the prescription also arise from writing prescriptions in a secret language coded with abbreviations and symbols. Only few pharmacists who are in secret liaison with doctors can decode the contents of prescriptions and dispense the medication. Although it was started with the good intension to curb the menaces of self-medication, it is misused to direct prescriptions to a particular medical shop. The prescriptions written contain various medicines with different pharmacological properties. It may happen so the patient is using different medications for a single indication. This is irrational drug abuse of prescription medicine (Nwolisa et al. 2006). Prescriptions need to be checked through the glasses of vigilant pharmacist who critically checks the prescription, dose of medicines, and any adverse drug reactions. The pharmacist with the background of medicines can easily identify the mistakes regarding dose, interactions, and indications of all the drugs as per the requirement of the patients. Many times it happens so that the medicines in prescriptions are found without any indication. For example, a patient who is suffering from cough and cold of viral infection is prescribed azithromycin (antibiotic) and paracetamol (antipyretic). The cough and cold with viral infection are not having symptoms of fever. It is irrational to prescribe antibiotic and antipyretic when there is no infection and fever. So such checking of prescriptions and referring back to prescriber are an important objective of prescription analysis. In some instances, there is a clear-cut indication for a medicine which is overlooked by the prescriber. In such instances, it becomes the duty of the pharmacist to draw the attention of the prescriber who may consider including a medicine for a skipped indication. For example, antiplatelet prophylaxis should be included for patient suffering from angina pain usually 75–150 mg of aspirin daily (low dose). Hence the prescription analysis is going to identify the cause and bring required alterations in the prescriptions. Prescription analysis is also required for optimizing the dose of a drug which can lead to identifying overdosing situations and promote the patients’ safety. The prescription analysis should be systematically carried out while dispensing the medicines (Schmidt 2019). In practice usually one can find the drug therapy problems which are given in Table 7.4 with examples. In recent time’s new technology, electronic prescriptions (e-prescription) are replacing the conventional paper prescriptions. The advantages of e-prescriptions over the paper prescriptions are discussed below. E-prescribing is getting popular in developed countries as the technology offers advantages to patients, physician, and community pharmacist. At the outset, it eliminates the prescription-based drug error due to handwriting errors and illegibility of prescription. Pharmacist can access prescription history, which minimizes the chances of wrong drug being dispensed. It supports automated clinical decision-making as it removes the guess work by prescriber as he/she has to fill out the dose, route of administration, strength of medicine, and frequency of administration. Prescriber can also check the doses and duplicate therapy as software alerts the prescriber. It has an access to drug dictionary

102

A. N. Nagappa and J. Kanoujia

Table 7.4 Potential drug therapy problems to look in prescription analysis Type of drug therapy problems Needing pharmacotherapy and not receiving it Taking or receiving the wrong drug Taking or receiving the too little of the correct drug Taking or receiving the too much of the correct drug Experiencing and adverse the drug reaction Experiencing in drug-drug or drug-food interaction Not taking and receiving the drug prescribed Taking or receiving a drug for no valid indication

Example Not treating with thiazide diuretic for premier essential hypertension Antibiotic for viral infections Low dose of ACE inhibitors in heart failures, as patient could benefit by higher dose System release antihypertensive for a patient with colostomy Beta-blockers for asthmatic patient Tetracycline and iron preparations/tetracycline with milk Failure to give prophylactic anti-angina therapy by monitoring glyceryl trinitrate (GTN) uses and angina attacks Not understood or remembered or agreed by the patients

and many other useful features assisting rational use of the drug. It also helps the healthcare providers in viewing the medication history and replaces manual reconciliation. It reduces the clerical burden of the pharmacist including filling the forms or pharmacy data and pharmacy benefit management. E-prescriptions reduce the waiting time of patients in the pharmacy. For example, as the prescriptions are sent directly to pharmacy for dispensing by the time patient arrives at pharmacy for collecting the prescription medicines, the basket of prescription medicines shall be kept ready for dispensing. Clinical alerts, drug interactions, duplicate therapy, and notifications of allergic reactions come automatically while prescribing on the screen of the prescriber (Porterfield et al. 2014; Fischer et al. 2008). Physicians can now track patient’s fulfillment of prescription by logging into the e-pharmacy database. As e-prescriptions are Transferred from clinics to pharmacy, there are no chances of losing the prescriptions. The privacy and protection feature in e-prescriptions is inbuilt, and one can check the medication adherence without the chances of misplacing the prescription. In pharmacy and clinics, e-prescription reduces administrative burdens and enables the pharmacies to dispense more prescriptions with ease. It also helps healthcare system by reducing the hospital readmission by built-in clinical alerts and duplicate therapy alerts. It addresses the issue of non-adherence and discontinuing with therapy and improves medication adherence. It is also simplifies verification status of health insurance, dispensing of medicines, and services as per the policy claims. Prescription analysis helps in mediating the irrational use of drugs; one can get an insight of overuse or underuse or misuse of prescription medicines; it can also identify the cases of polypharmacy wherein patients are consuming many medicines

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

103

at a time. It also helps in identifying and documenting inappropriate use of antibiotic and multivitamins. Prescription analysis helps in documenting the overuse of injections when alternative oral doses forms are available. One can check whether the clinical guidelines are followed while prescribing the medicines. It can also identify case of unnecessarily expensive medicines being prescribed instead of generic medicines (Abramson et al. 2011).

7.11

Therapeutic Drug Monitoring (TDM) Services

Therapeutic drug monitoring is a service provided by clinical pharmacy department on request of clinician, to learn how much of the drug administered is available in the body fluid after drug administration. Depending on the concentration of the drug in the body fluid, one can decide how much of the drug needs to be administered to build the plasma concentration within the therapeutic window (Fig. 7.3). Patient related factors affects the plasma drug concentration, one can prefer real-time plasma concentration instead of label-mentioned values. The real-time value of the plasma concentration enables them to calculate the efficacy and safety of a particular drug in individual patients. TDM may not be essential for each and every drug administered. For example, for drugs having lot of margin of safety, it may be not needed. TDM is clinical laboratory measurement of a drug with appropriate medical interpretation. It will directly influence the drug administration process and dosing schedule. The main aim of the TDM is to individualize the therapeutic regimen. It will be helpful in the management of drug therapy for curing, improvement, or prevention of disease and pathogenesis (Kang and Lee 2009). The basic necessity of TDM for any drug is to determine the relationship between the drug plasma concentrations and clinical effects. In case there is unclear relationship between the plasma concentration and its effects, TDM is of no value. If the therapeutic outcome can be precisely manifested depending on plasma 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Category 1

Category 2 Series 1

Series 2

Category 3

Category 4

Series 3

Fig. 7.3 Relationship between plasma concentrations and therapeutic outcomes

104

A. N. Nagappa and J. Kanoujia

Table 7.5 List of established TDM drugs S. no. 1 2 3 4 5 6 7 8 9

Drug Cardiac drug Cardiac drug Antibiotics Antidepressants Antiepileptic drug one Antiepileptic drug two Bronchodilators Anti-cancer drug Immunosuppressive

Example Amiodarone, digoxin, procainamide Disopyramide, procainamide, quinidine, lignocaine Gentamicin, amikacin, tobramycin Lithium, tricyclic antidepressants Phenytoin, phenobarbitone, benzodiazepines Carbamazepine, valproic acid, ethosuximide Theophylline Methotrexate Cyclosporine, tacrolimus

concentrations, then TDM is of great value. However when there is an unclear relationship on observed therapeutic outcome and plasma concentrations, it helps considerably in the management of the disease. One of the challenges to arrive at therapeutic range is how much to prescribe and guess the concentrations remained within the therapeutic window. But the target concentration is linked to a specific dose for an individual patient not for range of doses. In predetermination of target concentration, one should do the concentrationtherapeutic effect relationship with desirable and undesirable side effects. The target concentration is chosen for an individual patient to optimize not only for therapeutic effect but also for other outcomes of the drug therapy. To arrive at an optimal target concentration in individual inpatient selection of the target concentration is a first step. Prediction based on calculations about clearance and volume of distribution using the pharmacokinetic data along with findings of lab values of patients liver and renal function is important step. Calculation of the loading dose and maintenance dose to achieve the target concentration is an important step. Practically one should administer different doses and measure plasma concentration to understand the pharmacokinetic relationship in an individual patient. Simultaneously revision of the target concentration should be based on clinical assessment of the patients (Ghiculescu 2008) (Table 7.5). Therapeutic drug monitoring is indicated when there is uncertainty between dose and plasma concentration, for example, phenytoin in the treatment of epileptic seizure and epilepsy. It is also important for those drugs with the narrow therapeutic window, for example, lithium, digoxin, and phenytoin, to avoid toxic effects of drugs. In the case of the theophylline, TDM is required because the dose response curve is very steep. It is also indicated when side effects and toxicity are overlapping. For example, nausea and vomiting happen due to congestive heart failure as well as because of digitalis toxicity. In such cases, it is very much difficult to interpret the clinical evidence whether it is due to therapeutic or toxic effects. In drugs with saturable metabolism, absorption and elimination after certain concentration change from linear to nonlinear. In such condition, the prediction of the drug metabolism becomes highly unpredictable. In such circumstances, one should go for TDM. It is

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

105

also indicated for drugs with poorly defined responses or difficult to clinically relate dose with the response, for example, immunosuppressive drugs (Touw et al. 2005). It is very important to know that in kidney disease, there is an abnormal excretion pattern. In a normal person, the relationship between dose and plasma concentration is predictable, but in inpatient with kidney disease, this relationship gets altered. The TDM should be used for dosing the patients, for example, digoxin, lithium, and gentamycin. TDM is also important wherein drug interaction alters the relationship between dose and plasma concentration; for example, thiazide is known to increase plasma concentration of lithium. TDM is very useful in diagnosis of suspected drug abuse and drug toxicity cases. It can also be used in the evaluation of patient compliance; some drugs like antiepileptic, cyclosporine, and steroids require tapering of doses guiding the withdrawal of drug therapy. In such instance, TDM is indicated. Drugs that may not require TDM service are those having a large therapeutic window or index, where toxicity is not related to its plasma concentration, for example, anaphylaxis due to penicillin G. The effect of drug can be measured using functional laboratory test and where plasma concentration cannot be correlated to its clinical effect, for example, anticoagulants. The therapeutic effect of antidepressants can not be corelated with its plasma concentration. In another example, drugs like omeprazole and MAO inhibitors which act like hit-and-run drug TDM are of no use. The principles of TDM service consist of timely withdrawals of blood samples and measurement of serum/plasma drug concentration. The sample withdrawal intervals should be planned as per the dosing intervals. The loading dose and maintenance dose should be calculated. The drug administration based on pharmacological and pharmacokinetic profiles of the drug administration provides platform to initiate the TDM. Utilizing patient data like demography, clinical laboratory readings, history, and interpretations of serum or plasma drug concentration in previous admissions if available should be matched with above factors of patient, and individualized drug therapy should be tried. The process of TDM involves establishment of plasma profile of the patient following administration of predetermined dose of the drug, followed by collection of blood samples at definite intervals and determination of concentrations of drug in blood samples. Finally using the above data, one should develop plasma profile and pharmacokinetic model. The clinical effects, development of dosage regimen, and diagnosis should be able to predict the outcomes in a patient. Finally one should be able to select doses from the calculations derived from TDM and be able to provide a treatment with certainty and safety. The TDM-determined doses can be leading to the assessment of clinical response. The pharmacokinetic parameters that are of great importance in TDM are bioavailability, volume of distribution, plasma clearance, urine clearance, half-life of the drug, and protein binding of the drugs (Gross 2001). Therapeutic drug monitoring maximizes therapeutic efficacy of drugs and avoids toxicity of the drugs; it helps in identification of cause for therapeutic failures, due to noncompliance and sub-therapeutic dose. It helps in dose adjustment which is determined by the equation:

106

A. N. Nagappa and J. Kanoujia

New dose ¼ current dose
by desired Css =OldCss , TDM facilitates therapeutic effect of a drug by achieving target drug concentration. Therapeutic drug monitoring helps in establishing drug poisoning, drug toxicity, and drug abuse cases (Buclin et al. 2020).

7.12

Formulary Management

Drug formulary is a system wherein list of all medications is updated with useful information for treatments to be used by physicians, pharmacist, and nurses to assist in clinical judgments. It is also referred by paramedical in diagnosis and treatment of disease along with health promotion. Formulary system management is an ongoing process by a healthcare organization. The physician, pharmacist, and nurses along with other healthcare providers in a hospital establish the policies regarding the use of drug product along with accepted therapies. While selection of drug therapy and drug product, one should consider the criteria of cost-effective and most medically appropriate medicine have to be selected to serve the health interest of the patients coming to hospital. Formulary system management is a well designed to guide physician to prescribe the safe and effective drugs for a particular conditions. The objective of formulary management is to cut the unnecessary cost of medicines and assure acceptable quality care. It also aims at providing information on clinical uses of drug products and provides information about organization policies and procedures for prescribing the medicines in the hospital. It is also accepted that the formulary management is suitable for small and big hospital and for specialized hospitals of kidney, heart, liver, and lung hospitals. It has established approved protocols and guidelines of specific disease conditions (Scroccaro 2000). The formulary management team should work on continuous improvement to provide latest information of latest drugs or removal of old drugs from market. It helps in propagation of changes in hospital policies and procedures. Updating of formulary managements helps in information of latest clinical trial guidelines of uses and safety of drug in healthcare. Advantages of formulary management system ensure quality, and irrational use of drugs updates the healthcare providers with latest knowledge about effective drugs. It helps in reducing the cost of the treatments; the main disadvantage of formulary management is compromising the patient care limiting the doctor’s choice of medicines and prescribing authorities. Principles of drug product selection are based on scientific evidence by comparing other similar drugs; the formulary management emphasizes on scientific evidence and consideration of effectiveness, safety, and cost of a drug. Activities in formulary management include addition of newly approved drugs and deletion of the old drugs. Review of new information regarding safety and efficacy of the drugs included in the formulary. Formulary management also engages in tracking prescribing using non-formulary agent (Lehmann et al. 2007).

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

107

It is also important to prepare and review single drug with other drugs that are therapeutically competitive; in therapeutic class review, comparison and contrast of all the drugs in a single class are carried out. For example, anti-hypertensive here is focused not on a single drug. Formulary monograph is different from pharmacopoeia monograph. The pharmacopeia monographs aim at providing the legal requirement of an active pharmaceutical ingredients and official formulation, from the point of regulation and manufacture of the formulation, whereas formularies are aimed at giving ready-touse information for practitioner in healthcare settings (Campbell 2005).

7.13

Conclusion

The clinical and hospital pharmacy services are vital to achieve the best outcome and safety among the in patients and OPD patients. The skills set of pharmacist are different and depend upon the contents of services provided by the department. For example, hospital pharmacy focuses on running of a ward pharmacy and satellite pharmacy, compounding, and bulk formulation manufacturing for the in-house use of hospital. Clinical pharmacist is engaged in ward rounds, drug information services, prescription analysis, patient counseling, and discharge medication counseling.

References Abramson EL, Barrón Y, Quaresimo J, Kaushal R (2011) Electronic prescribing within an electronic health record reduces ambulatory prescribing errors. Jt Comm J Qual Patient Saf 37(10):470–478 Ali A, Yusoff S, Joffry S, Wahab M (2013) Drug information service awareness program and its impact on characteristics of inquiries at DIS unit in Malaysian public hospital. Arch Pharma Pract 4(1):9–14 Alomi YA, Alghamdi SJ, Alattyh RA (2018) National Workload Analysis of network of drug information centers at Ministry of Health hospitals in Saudi Arabia. Int J Pharmacol Clin Sci 7(4):17–25 Beena G, Padma R (2005) Assessment and evaluation of drug information services provided in a south Indian teaching hospital. Indian J Pharm 37(5):315–319 Buclin T, Thoma Y, Widmer N, André P, Guidi M, Csajka C, Decosterd LA (2020) The steps to therapeutic drug monitoring: a structured approach illustrated with Imatinib. Front Pharmacol 11:177 Campbell HE (2005) Clinical monograph for drug formulary review: erectile dysfunction agents. J Manag Care Pharm 11(2):151–171 Chauhan N, Moin S, Pandey A, Mittal A, Bajaj U (2013) Indian aspects of drug information resources and impact of drug information Centre on community. J Adv Pharm Technol Res 4(2): 84–93. https://doi.org/10.4103/2231-4040.111524 Christensen DB, Farris KB (2006) Pharmaceutical care in community pharmacies: practice and research in the US. Ann Pharmacother 40(7–8):1400–1406 Churi S, Abraham L, Ramesh M, Narahari MG (2013) Evaluation of poison information services provided by a new poison information center. Indian J Pharm 45(5):496–501

108

A. N. Nagappa and J. Kanoujia

Davidson C (2015) Drug information and literature evaluation. J Med Libr Assoc 103(1):59. https:// doi.org/10.3163/1536-5050.103.1.015 Descotes J, Testud F (2005) Toxicovigilance: a new approach for the hazard identification and risk assessment of toxicants in human beings. Toxicol Appl Pharmacol 207(2 Suppl):599–603 Dirin MM, Mousavi S, Afshari AR, Tabrizian K, Ashrafi MH (2014 Jul) Potential drug-drug interactions in prescriptions dispensed in community and hospital pharmacies in east of Iran. J Res Pharm Pract 3(3):104–107. https://doi.org/10.4103/2279-042X.141118 Drug Information Center Karnataka State Pharmacy Council (2007) Setting up of drug information centers in selected states in India. Karnataka State Pharmacy Council, Bangalore, pp 5–6 Ellington L, Matwin S, Jasti S, Williamson J, Crouch B, Caravati M, Dudley W (2008) Poison control center communication and impact on patient adherence. Clin Toxicol (Phila) 46(2): 105–109. https://doi.org/10.1080/15563650701338914 Fischer MA, Vogeli C, Stedman MR, Ferris TG, Weissman JS (2008) Uptake of electronic prescribing in community-based practices. J Gen Intern Med 23(4):358–363 Ghaibi S, Ipema HGM (2015) ASHP guideline on the Pharmacist’s role in providing drug information. Am J Heal Pharm 72:573–577 Ghiculescu R (2008) Therapeutic drug monitoring: which drugs, why, when and how to do it. Aust Prescr 31:42–44. https://doi.org/10.18773/austprescr.2008.0 Gross AS (2001) Best practice in therapeutic drug monitoring. Br J Clin Pharmacol 52:5S–10S Grossman S, Nathan JP, Ipema HJ, Ness GL, Tierno HE, Gabay MP, Calip GS (2020) Survey of drug information centers in the United States–2018. Am J Health Syst Pharm 77(1):33–38 Hansen KN, Nahata MC, Parthasarathi G (2004) Drug information. In: Rajendran SD (ed) A textbook of clinical pharmacy practice, essential concepts and skills, 1st edn. Orient Longman, Andhra Pradesh, pp 267–286 Kang JS, Lee MH (2009) Overview of therapeutic drug monitoring. Korean J Intern Med 24(1): 1–10 Lall SB, Peshin SS (1997) Role and functions of poisons information Centre. Indian J Pediatr 64(4): 443–449 Lehmann DF, Guharoy R, Page N, Hirschman K, Ploutz-Snyder R, Medicis J (2007) Formulary management as a tool to improve medication use and gain physician support. Am J Health Syst Pharm 64(5):464–466 Miller G, Franklin BD, Jacklin A (2011) Including pharmacists on consultant-led ward rounds: a prospective non-randomised controlled trial. Clin Med (Lond) 11(4):312–316. https://doi.org/ 10.7861/clinmedicine.11-4-312 Nwolisa CE, Erinaugha EU, Ofoleta SI (2006) Prescribing practices of doctors attending to under fives in a children's outpatient clinic in Owerri. Nigeria J Trop Pediatr 52:197–200 O’Hare JA (2008) Anatomy of the ward round. Eur J Intern Med 19(5):309–313 Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, De Sarro G, Gallelli L (2013) Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci 18(7):601–610 Pandey AA, Thakre SB, Bhatkule PR (2010) Prescription analysis of pediatric outpatient practice in Nagpur city. Indian J Commun Med 35(1):70–73. https://doi.org/10.4103/0970-0218.62564 Perversi P, Yearwood J, Bellucci E et al (2018) Exploring reasoning mechanisms in ward rounds: a critical realist multiple case study. BMC Health Serv Res 18:643 Porterfield A, Engelbert K, Coustasse A (2014) Electronic prescribing: improving the efficiency and accuracy of prescribing in the ambulatory care setting. Perspect Health Inf Manag 11:1g Raehl CL, Bond CA, Pitterle ME (1998) Clinical pharmacy services in hospitals educating pharmacy students. Pharmacotherapy 18(5):1093–1102 Schmidt CWP (2019) Prescription analysis. In: Pediatric oncologic pharmacy. Springer, Cham Scroccaro G (2000) Formulary management. Pharmacotherapy 20(10 Pt 2):317S–321S Shafiekhani M, Moosavi N, Firouzabadi D, Namazi S (2019) Impact of clinical pharmacist's interventions on potential drug–drug interactions in the cardiac care units of two university hospitals in shiraz, south of Iran. J Res Pharm Pract 8:143–148

7

Clinical Pharmacy Services: Drug and Poison Information, Ward Round Partici. . .

109

Shields KM, DiPietro NA, Kier KL (2011) Principles of drug literature evaluation for observational study designs. Pharmacotherapy 31(2):115–127 Stoukides CA (1993) Drug information centers in the United States. J Hum Lact 9(2):117–120 Tefera YG, Gebresillassie BM, Ayele AA et al (2019) The characteristics of drug information inquiries in an Ethiopian university hospital: a two-year observational study. Sci Rep 9:13835. https://doi.org/10.1038/s41598-019-50204-1 Touw DJ, Neef C, Thomson AH, Vinks AA, Cost-Effectiveness of Therapeutic Drug Monitoring Committee of the International Association for Therapeutic Drug Monitoring and Clinical Toxicology (2005) Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 27(1):10–17 Yu X, Chu Z, Li J, He R, Wang Y, Cheng C (2021) Pharmacokinetic drug-drug interaction of antibiotics used in sepsis Care in China. Curr Drug Metab 22(1):5–23

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication Review, Treatments of Minor Ailments, Screening and Monitoring of Chronic Disease, and Maintaining of Patient Profile A. N. Nagappa and Jovita Kanoujia

Abstract

Community pharmacy is the core of pharmacy service wherein the pharmacy profession is engaged directly with the community. Community pharmacists are considered as the public face of the pharmacy profession. They are engaged in activities like dispensing, minor ailments, referrals to hospitals, interaction with prescriber in case of need, patient counseling, and education. They are also engaged in medication review and also home medication review. They are also supposed to maintain adequate inventory of required medicine as it has direct effect on pharmacy business. The model of pharmacy may be independent or chain pharmacy. Community pharmacists have earned recognition by the quality services they provide to the patient and fame to the profession. Keywords

Dispensing of medicine · Pharmacy practice · Ideal pharmacy layout · Inventory management · Home medication reviews

8.1

Community Pharmacy Services: Dispensing of Prescription

Community pharmacy is an organization that is usually established and owned by a registered pharmacist to serve the need of the community of drug product and pharmaceutical services. It may be an independent pharmacy, may be a part of the corporate pharmacy chain, or may be a part of supermarket. There are different models of community pharmacy setups. Community pharmacy is growing, due to new drug products, increased number of patients, increase in economic growth, and A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_8

111

112

A. N. Nagappa and J. Kanoujia

demand for quality of life and finally demand for new knowledge to avoid diseases. As a result of advancement in research and technology and increase in population especially in developing countries, good facilities of healthcare are becoming less available to the public. The increased patient load in hospitals leads to a long waiting time for getting healthcare. With healthcare being expensive in developed countries, patients are looking at corporate hospitals in developing countries as an alternative. The emergence of a new flourishing business called medical tourism has been very successful (Melton and Lai 2017; Black et al. 2009). Whenever a P & HC needs healthcare assistance, he/she immediately visits community pharmacy and seeks the advice of the pharmacist. After making a preliminary observation and discussion with the patient, the pharmacist makes out whether the patient is having a minor ailment or a serious condition. If the patient is having a minor ailment, the pharmacist will advise the patient and also provide with OTC medicine for the management of the condition. In many cases, hospitalization may not be required; assessment of the patient condition as a minor ailment or major disease is carried out by the community pharmacist. The advantage of visiting a community pharmacy and seeking advice is that it is much simple when compared to visiting doctors directly and getting examined thoroughly in a hospital. In a clinic, a patient has to book an appointment and wait for his/her turn for consultation. However in a pharmacy, without any appointment one can meet the community pharmacist and get his/her problems explained and resolved. There are many new diseases which are haunting the public, and there are no well-established therapeutic treatments for such diseases. During such times, there is panic, and under such circumstances, a pharmacist helps the public by advocating preventive and prophylactic measures that protect and prevent the spread of diseases in the community (Bosse et al. 2003). Professional services rendered by the community pharmacist as a guardian of the community have earned respect and recognition in the community. The community pharmacist enjoys a special status and patronage of the community as “My Pharmacist.” In a community pharmacy, various activities and services are carried out to help the public. The core of dispensing medicines against prescriptions includes activities from filling of prescription to teaching patients how to handle and use the medicine. Other activities apart from prescription handling include patient counseling, pharmacy administration, compounding of medicines, providing of health information to P & HC, patient medication records, vaccination services, family planning services, and drug information services. Community pharmacy has emerged as the public face of pharmacy profession in modern times. The location of community pharmacy dictates its success. Location of community pharmacy should be in such a place that it should be easy for the public to visit and access the services. Location analysis before establishing a community drugstore should consider the following points: Is it near a place where most of the community people likely visit or go nearby for one or other needs? For example, is it a place near the market, bus stand, or railway station? Is it near a hospital, district, or municipal hospital where large number of patients visit for their healthcare needs? Other logistics to consider are about the total population of the community, income of

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

113

Fig. 8.1 Layout design of an ideal community pharmacy

the population, and competition for the pharmacy. Business locality, flow of traffic, expectation for special services, and type of customers may also need to be considered. Good location of the pharmacy can lead to success and selection of poor location may lead to failure of the pharmacy (Negru et al. 2010; Law et al. 2011). The layout design for a good community pharmacy is given in Fig. 8.1. In the layout design, there should be thorough consideration for exterior and interior designs. The design should appeal to the public that the pharmacy is very clean and hygienic. The design should be built in considerations for the convenience of patients and business of pharmacy. It should be having almirahs and cupboard with or without glass windows. Almirahs or cupboard should be having lock and key to prevent pilferage and pests/rodents. The pharmacy should have air-conditioning as many medicines are temperature sensitive and start deteriorating at higher temperature of more than 27
C. Biological drugs like insulin, vasopressin, erythropoietin, and vaccines need to be stored in a refrigerator between 2 and 8
C (Mathew et al. 2013). The geographic locations of a community pharmacy may be either urban or rural area. In urban areas due to high population, there is a need for more investment, and rural areas require less investment due to less business. The practical location near airports, hotels, and resorts helps the pharmacy to get business from floating population. The major factors to be considered in location analysis of a community pharmacy are logistic facilities, labor supply, electricity, safe drinking water, and nearby banking facilities. Availability of wholesalers nearby and their services may help in reducing time and investments on stocks. If the pharmacy is located near industries, residence colonies, recreation facilities, universities, and other educational facilities, the business may be limited, and accordingly one should build one’s inventory as per the demands of the community. Pharmacies can attract more number of public to visit and buy medicines. Finally larger market and non-dependency on doctors for prescription can lead to successful results in

114

A. N. Nagappa and J. Kanoujia

community pharmacies (Gregory et al. 2000). Establishing and managing a successful community pharmacy require not only pharmacy knowledge but also basic principles of financing, inventory management, and store management skills. This is important in a pharmacy unlike other general stores. Pharmacy business depends on prescription or doctors who are influenced by the pharmaceutical industry. It is also important to know that medicines are perishable and have a date of expiry which means economic loss for the pharmacy. Other overhead expenses like rent, salary to staff, electricity bills, and taxes recur expenditure of a pharmacy. One should be able to earn profits after discounting from investments and expenditure. He/she should commit and follow financial discipline with his/her vendors or wholesale suppliers. He/she should be having enough reserve money to run the pharmacy and earn a goodwill by his/her timely repayments of the bills. The turnover of products by sale is key to the success of a pharmacy. The major revenue for a pharmacy comes from the margin of profits on turnover of sales. The retail pharmacy earns a profit of 20–30% margin on the sale of prescription medicine. If the product is seasonal, then the sale may become slow, and the product remains unsold in the shelves of the pharmacy for a longer period. Unsold stock in the pharmacy increases the inventory cost of the product which may lead to financial loss to the pharmacy. Most of the finance for a pharmacy is borrowed from banks under conditions like mortgage and pledge of the personal properties (Urbonas et al. 2015). Capital is the asset in a business to produce income. It may be in the form of working capital liquid assets, securities, and bank overdraft facility, for example, cash on hand, inventories, and marketable securities. Fixed capital is properties and assets like land, building, or any other commercial place. Risk management and insurance for a community pharmacy provide securities for the business. The risk is the possibility of losing value, like loss of health, social status, emotional well-being, or financial wealth. Market risk is due to change in economic conditions and exogenous risk, like, flood, fire, or earthquake, damaging the value of the pharmacy. Community pharmacy has an investment and inventory of several lakhs of rupees. Risk to pharmacy may arise in the form of theft, natural disasters, or fire. Risk management of community pharmacy is important in order to avoid and overcome possible risk. One can buy adequate shop insurance to protect from natural calamities. Common approaches of risk management of community pharmacies include avoiding and reducing the risk. After the risk has happened one should either accept or transfer the risk; accepting the risk means taking a risk of loss where the cost of insuring loss against the risk could be greater over time than the total losses incurred (Wiśniewski et al. 2020). Transferring the risk means buying the insurance policy for unexpected accident or loss; usually general insurance is done for community pharmacy for its moveable and immoveable assets to provide risk cover. The pharmacy is supposed to buy its stocks of medicine from licensed wholesalers, C & F agents, company-authorized stockists, and company warehouses. Medical representatives and pharma marketing officials coordinate the sale of medicines to the community pharmacy. They also generate prescriptions and help in the movement of the stock. They should never be

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

115

tempted to buy medicines from unauthorized persons who are offering the goods at a discounted price. It may be a counterfeit or duplicate medicine. It is an offense to buy medicines in the open market from an unauthorized dealer. It is mandatory for the pharmacist to keep the address of the supplier and it should be produced on demand by regulatory agencies and court. The objective of purchasing should be to ensure a steady supply of medicines and not run out of stock. The patient does not like this and is not interested to visit another pharmacy to fill the prescription of nonavailable medicine. It is very much important to review the stock situation and order the medicine before it goes out of stock. It is also important that if a prescription medicine is not available, then it is loss in profit and business opportunity. In such situations, the pharmacist should try to buy the medicine in a nearby pharmacy and should try to dispense the complete prescription. This will impress the patient and wins loyalty for the pharmacy. Pharmacists should develop a strong communication network of fellow pharmacists and wholesalers. Maintaining the standards of quality improves the image of the pharmacy and attracts good number of customers leading to the success of the pharmacy. Community pharmacists should be alert and avoid duplication of order and should manage expired goods. One should check every supplied medicine for correctness of billing and date of expiry. If the supplied stock is near expiry, the pharmacist must alert the supplier and the medical representative. He/she should also maintain a very good relation with vendors who supply medicines to his/her pharmacy. Record keeping of medicines bought and sold should be maintained properly for accounting and regulatory purposes (Gammie et al. 2016; World Health Organization 2019). Community pharmacists should always buy stocks from official wholesalers. Pharmacists should never buy stocks from unauthorized sources. It may lead to stocking of counterfeit medicines. The pharmacist should always buy right quality and right quantity at the right time for a right price. The principles of purchasing state that one should buy like a poor and sell like a rich. Good purchasing practice is very important for the success of a pharmacy.

8.2

Purchasing Procedure

1. Purchase requisition: The list of products to be purchased is made based on the product flow and patient request. 2. Selection of the supplier: The right source is selected based on the quality and economic values. 3. Placing order: After requisition slip and supplier selection, the order is placed in the desired date and time. 4. Receiving and checking materials: The products received should be properly checked and verified for the condition and quantity of the products received. 5. Checking of invoice and bills: The invoice and bills of the products received should be checked and verified for quantity and billing amounts.

116

A. N. Nagappa and J. Kanoujia

6. Recording of bills: Proper record keeping of all the bills should be done for future use and audit purpose.

8.3

Methods of Purchasing Pharmaceutical Products Required by the Buyers for a Future Date

1. Purchasing by requirement: Products are purchased when necessary and in exact quantities required. 2. Purchasing for specified future period: Products are purchased for a limited time on a contract basis. 3. Purchasing from a favorable market: Products are purchased when the market is favorable or when products are available at low price. 4. Speculative purchasing: Products are purchased when the price of the products goes down and sold when the price rises. Surplus (additional) quantity is purchased to get more profit. 5. Contract purchasing: Products are purchased through direct contract, ensuring continuous supply of the products. Contract purchases have a fixed delivery date and price. 6. Purchasing small items in groups: Products are purchased in small quantities when required. It saves larger expenses. 7. Scheduled purchasing: Products are purchased in a predetermined schedule or date. In this method, suppliers keep the stock ready.

8.4

Inventory Control

Inventory control assures maximum customer service of filling prescriptions; reduces the cost on inventory investment, operational cost, and store space in the pharmacy; and finally optimizes the wastage and surplus stocks. One should strive to fill all the prescription that comes to the pharmacy. Pharmacists are responsible for procuring and stocking medicines. They should keep all the medicines that need to be dispensed. However, it is impossible to stock each and every medicine, and hence many times prescriptions go undispensed, causing loss of opportunity for the pharmacy. It is also important to estimate the residence time of ordered medicine in the shelf of the pharmacy. This is because the product which remains for a long time in the shelf of the pharmacy is the cause for concern. This would increase the cost on inventory, and if the product gets expired in the pharmacy, it causes financial loss. One cannot dispense an expired medicine, and vendor also refuses to compensate for the expiry of medicine. There should be a close built-in mechanism for procuring the medicines from stockists and wholesalers. It is always better to have a commitment with medical representative to help and reimburse in resolving expired goods in the pharmacy. This would save the pharmacy from incurring heavy losses due to expiry of medicines (Lindley and Mackowiak 1985).

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

117

Inventory management practice is a requirement for all types of pharmacy. There are good software available for subscription which helps one to do the routine work of the pharmacy in a systematic manner. The software can be installed for inventory control that may have provision for important data on dose regimen, doses, and ADR which can be useful as a ready reckoner for dispensing of the medicine. One-time entry of data of purchase, date of sale, discounts, and margins of profit need to be computed. There are a couple of approaches of inventory control which can be installed depending on the features and utility (Murphy and Yemen 1986). 1. Economic order quantity technic (EOQ): In the EOQ technique, appropriate quantity for purchasing in each lot is determined, where the total cost of holding pffiffiffiffiffiffiffi inventory is also kept minimum. The equation is EOQ ¼ 2AO where A is the C annual requirement of the product, O is the ordering cost per order, and C is the carrying cost per unit. 2. ABC analysis: In the ABC analysis, purchasing decision is based on the cost of the product and quantity of the product; products are classified into AB and C based on the cost and number of units required. A is the list of medicines which are very expensive; medicines that are moderately expensive are put in the category B, and C category comprises drugs that are very cheap. 3. Redline method: A line is drawn inside the box, and the label of reorder and inventory order is placed when the stock falls below the red line. After every withdrawal from the bin, it is recoded by the computer, and inventory balance is updated. 4. Minimax system: In the Minimax system, labels of maximum inventory and minimum inventory are set. Maximum label guarantees safety stock, and minimum label indicates reorder point. It is important to manage inventory labels to not cross the set limits of maximum and minimum labels.

8.5

Home Medication Review (HMR)

Patients who are discharged from hospitals, patients who are staying at home, and patients who are unable to visit hospitals are deprived of monitoring of disease condition. It is expected that patients themselves self-manage their condition. It is observed that many times patients are unable to manage their conditions and require a professional assistance to manage and care them. Due to the demand for health services for the above patients, HMR has evolved. HMR is a triangle service involving doctors, pharmacists, and patients. The main objective of HMR is to apply latest knowledge with practical skills of a doctor and pharmacist to provide and implement the protocol. The pharmacist and doctor shall take such steps in order to minimize the risk and improve safety for an individual patient (Papastergiou et al. 2013; Basheti et al. 2013). Patients will not be able to understand about medication-related practices and need a professional guidance. Conventionally patients should get this service during

118

A. N. Nagappa and J. Kanoujia

Fig. 8.2 Process of home medication review (HMR)

dispensing counseling sessions in the community pharmacy. But actual supervision and guidance are also needed. When a pharmacist visits patients in their own home, the patient communicates more openly and the pharmacist can observe the patient’s habits and condition closely and identify the health needs of the patients (Lau and Dolovich 2005). The key advantage of HMR is that one can directly observe the patients and their response to treatments (Fig. 8.2). If any ADR is happening in the patient, then the pharmacist can become alert and inform the patients and doctor regarding the ADR of the drug prescribed to the patient. This will optimize the use of medicines which is usually not possible in a conventional setting like doctors’ clinic or primary health centers. In a conventional setting, a patient visits and stays for a few minutes with the doctor. During this time, the doctor should see the patients and decide upon the patient condition and also look into the report and discuss with the patient for any symptoms bothering the patients. In this brief interview, the doctor has to decide upon patient medications and revise the prescription if it is necessary. Usually there will be a big queue of patients with appointments to be seen by the doctor. Under such circumstances, a doctor has to decide regarding the patient medication and explain them how to use the medicines. Many times the doctor may not be able to give all the information to the patient. In HMR service, all these shortcomings shall be handled professionally. The HMR model involves a community pharmacy, a licensed pharmacist, and general practitioner. The pharmacist must be specially trained and accredited by a regulatory agency so that the services of HMR are uniform and standard (AbuNaba'a and Basheti 2019). The objective of the HMR is to detect drug-related problems that interfere with the desired patient’s outcomes in order to optimize medicaments, which the patients receive after seeing the doctor who hands over the prescription. The prescription being a technical document contains the name of medicines, doses, dose regimen, and instruction to the community pharmacy to dispense the medication. When a patient starts using the medicines at home, the medicines start showing its effect.

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

119

Due to the individual response of patients, the latter may show varied ADR. For example, drug used in the treatment of allergy, cough, and cold may show a strong drowsiness in a patient. Drowsiness may be very strong in some patients, and they may become quite inactive during the normal working hours. Patient may not be able to do regular activities; in such circumstances, the HMR can identify and refer the case back to doctors who try to minimize the response of the patient. HMR can improve the knowledge and understanding of doctors and patients about medicines. In this model, the health of patients who have been slandered is improved; HMR encourages team spirit and collaborative care which supplements each other’s knowledge and optimizes healthcare delivery (Gilbert et al. 2002). HMR is indicated for the patients who are either using more medicines for multiple indications or supposed to take more doses in a day; this becomes important because the patient usually gets confused and is prone to commit mistakes in using medicines as per the instructions. In such circumstances, the patient is likely to feel ill again due to inappropriate doses of medicines. It is also observed that when patients are using medicines for a long time such as in diabetes and hypertension, there is a possibility of change in the patient conditions which may require review of the disease and medicines; if such change in condition is ignored, it may be harmful for the patient. It is important to have a continued observation of the patient conditions which is not a waste of resource. It is necessary to closely monitor the patients who are using very potent drugs, like digitalis and methotrexate. For example, if the patient is suffering from rheumatoid arthritis, he/she is likely to be prescribed nonsteroidal anti-inflammatory drugs for symptomatic relief of pain and inflammation. Methotrexate is a diseasemodifying agent and an antirheumatic drug. The dose regimen of DMARD needs monitoring as the toxicity of methotrexate can suppress the immune system and the patient becomes prone to infections; hence the curative effect of methotrexate and harmful effect of immunosuppression should be balanced (Bodenheimer et al. 2002). In several cases, the patients may have difficulty in managing their own medicines due to illiteracy, language barriers, or poor sight or hearing. In such circumstances, it is very essential to assist the patient and family members to administer the prescribed regimens as per the rational principles. If a patient is suffering from several comorbidities, there will be several doctors attending that patient. It is very essential to coordinate among different doctors and update the patient conditions. It is usually observed that when multiple doctors are attending a patient, there shall be a polypharmacy. In such circumstances, a pharmacist reviewing the medication and observing the patient conditions should be on alert. In this process, the pharmacist in charge also makes an observation of suboptimal response to treatment with medicines. He/she also identifies issues of noncompliance, address them only if there are any difficulties for the patient to use the therapeutic devices, and attends to it by giving counseling. HMR for chronic disease, diabetes type 2 with hypertension, or any other conditions are properly implemented in patients, and Tables 8.1 and 8.2 demonstrate the same (Van Der Wal et al. 2006).

120

A. N. Nagappa and J. Kanoujia

Table 8.1 Home medication review questionnaire for type 2 diabetes mellitus with hypertension S. no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Congestive heart failure specific questions If the patient is on dash/diabetic diet plan, do they have access to “as-required” diuretics? Is the patient able to adhere to the diet plan? Does the patient have reliable set of targets for FBS, PPBS, and systolic and diastolic blood pressure? Can the patient reliably achieve a set of targets for FBS, PPBS, and systolic and diastolic blood pressure? Is the patient adhering to fluid restriction? Is the patient adhering to salt restriction? What is his/her level of activity? How many cups of coffee/tea and caffeinated beverages and drinks does the patient have in a day? Does the patient recognize the warning signs of diabetes and hypertension, for example tingling sensation in the legs? If the patient is on thiazide diuretics (furosemide) and metformin? If the patient is on insulin and ACE inhibiters/ARBs? Does the patient complain of any dizziness or lightheadedness and do they recognize hypoglycemia and hypotension? Do they know what to do during a dizziness and lightheadedness episode? Is the patient’s blood pressure controlled to target? If the patient is on an angiotensin II receptor blocker, is there a valid reason for why an ACE inhibitor was not prescribed? If the patient is on a combination of an angiotensin II receptor blocker and an ACE inhibitor, are they having regular potassium and renal function monitoring? Does the patient have an emergency action plan in case of emergencies such as chest pain? Do they monitor diabetes mellitus and hypertension by HbA1C and BP and BMI? Do they practice adequate physical activities like walking, yoga, meditation, and pranayama? Are the patients sensitive for complications of neuropathy, retinopathy, nephropathy, diabetic fat, and infection? Have the patients been checked for dental issues, corneal examination, and evaluation of neurons and kidney functions? Do they understand the relationship between the amount of carbohydrate and common salt and the relationship between hyperglycemia and hypertension? Do they understand the importance of salad, sprout, nuts, and lentils and legumes in the management of diabetes and hypertension? Do they practice any home remedies (clove, bitter guard, garlic, cinnamon, curry leaves, and blueberries) for the management of diabetes and hypertension?

Table 8.2 Adverse drug reactions of oral anti-diabetes Class of drug Biguanides Sulfonylureas

Subclass Metformin Glyburide (glibenclamide) glipizide, glimepiride, gliclazide

Main ADR GI symptoms (20–30%): Lactic acidosis Hypoglycemia, weight gain, avoiding renal insufficiency, caution in elderly

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

8.6

121

Minor Ailments

It is very common for a health consumer to visit pharmacy whenever he/she requires health assistance such as for treatment of mild diseases like cough, cold, and fever. Community pharmacists are responsible to provide primary healthcare and provide symptomatic relief by suggesting over-the-counter medicines (non-prescription medicines) to P & HC who visit the pharmacy for medical help and advice. Community pharmacists are well aware about the signs and symptoms of illness and have the task to distinguish between minor ailment and major disease. Minor ailments indicate slight illness or emergency which is of nonserious nature. When the patient is presented in the pharmacy for the management of illness, the pharmacist observes the patient and enquires how he/she is feeling and what is the problem. The pharmacist should also ask the patient what are the symptoms and does he/she has a fever, malaise, or any other symptoms bothering. Further if the patient has got an injury, immediately first aid should be given. In case it is suspected that the patient is having an infectious disease especially viral respiratory disease like viral influenza or swine flu, one should immediately take precautions about spreading of the disease. If the pharmacist observes any deviations of health through vital signs and symptoms, he/she should be alert to refer the patient immediately to a hospital (Ayele et al. 2018). While interacting with the patient, the pharmacist should use the opportunity to promote health education for the patient. The pharmacist should be able to understand sentimental feelings of patients and their family members by respecting the beliefs of patients and family members. The pharmacist should never hesitate to provide help and assistance to family members in coping up with the situation and should mentally prepare family members to take care of the patient at home. Minor ailments can be classified as general and systemic aliments. General aliments include common accidents and emergencies which need immediate first aid; however, in this category we have injuries and falls, dog bites, burns, high fever, heat stroke, diarrhea, fainting, etc. (Table 8.3).

8.7

Management of Minor Aliments

When the patient presents himself/herself in the community pharmacy, the pharmacist should be chatting with the patient to develop confidence and feel positive. He/she may ask how the incident had happened, how the patient got the disease, and something regarding the history of the illness. This will give an opportunity for the community pharmacist to learn about patient conditions and assess the severity of the disease. The pharmacist also needs to perform a quick physical examination and should try to find the cause of the disease and assess the condition which helps in making the care plan and instruction. After providing symptomatic treatment with OTC medicines (non-prescription medicines) depending on the situations, the patient may be given paracetamol tablets if he/she is having pain and fever, cetirizine if he/she is having cold or cough, and loperamide if he/she is having diarrhea. The

122

A. N. Nagappa and J. Kanoujia

Table 8.3 Minor ailments of eye accidents, infections, poor eyesight, dry eyes, night blindness, ear, otitis media, discharge, and deafness Classification of minor ailments Eye Eye accidents Foreign bodies Infections Poor eyesight Dry eyes Night blindness Respiratory tract Allergic rhinitis Common cold Sinusitis Sore throat Cough Dyspnea Chest pain Asthma Digestive system Toothache Stomatitis Soreness in mouth Constipation Diarrhea Indigestion Vomiting Abdominal pain Intestinal Obstruction Hemorrhoids

Ear

Earache Foreign body Otitis media Discharge Deafness

CVS

Hypertension Anemia Rheumatic heart disease Burning micturition Retention of urine Urinary infection Renal stones

Urinary system

Neuromuscular system

Headache, backache Convulsions Epileptic fits

Reproductive system

Heavy bleeding Sores and discharges Breast lump Dysmenorrhea

main objective of the above interview is to decide upon whether the patient condition mandates hospital admission or not. If the pharmacist by his/her experience is able to assess the patient conditions and guide the patient regarding admissions to a hospital, it is considered as a major contribution to the healthcare system. The pharmacist shall be helping in reducing the burden on the healthcare system. We all know that hospitals are overcrowded with patients and it is in the interest of patients, doctors, and hospitals that health problems of patients get resolved by the treatment provided by the pharmacist. It would be a great help to patients as they need not get admitted in a hospital to resolve the health issue (Welle-Nilsen et al. 2011). The community pharmacist can follow certain predecided treatment protocol; for example if a patient presents with complaints of fever, at first the pharmacist shall examine vital signs like the pulse rate, respiratory rate, body temperature, and blood pressure of a patient. It should be within the normal range; if it is highly abnormal then it will indicate that the patient condition is getting very serious and needs immediate medical care. The pharmacist also gathers information about headache,

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

123

nausea, vomiting, shivering with cold, running nose, allergies, skin infection, jaundice, and jaundice fits and cough. The pharmacist should advise the patient to take adequate rest and eat light meals so that body gets complete rest. He/she can also prepare a blood slide of the patient and examine for any malarial parasite. Patient should be given paracetamol tablet every 6–8 h depending upon the symptom of fever. In case the fever exceeds 102
F then tepid sponge treatment should be initiated in order to bring down the fever. The patient should be advised to take plenty of fluids like water and fruit juices. The patient should be advised to monitor and record the pattern of fever for 2 days. If the fever still continues then the patient should be advised to go to hospital for treatment; if the patient shows up with skin rashes, then he/she may be suffering from viral infection which can spread to others. In such conditions, the patient should be isolated at home. In case of uncontrolled high fever, the patient may show symptoms of delirium, convulsion, and unconsciousness; then the patient may be suffering from hyperpyrexia which is a medical emergency, and admission to hospital should be immediate (Hammond et al. 2004; Whittington et al. 2001).

8.8

Sun Stroke

Heat stroke is also known as sun stroke, wherein a person’s body temperature exceeds 40
C or 104
F; heat stroke can kill or cause brain damage or other internal organ damage. People who are aged above 50 are more sensitive than healthy young ones. In heat stroke, a patient usually complains of cramps, fainting, and heat exhaustion. It usually results from prolonged exposure to high temperature accompanied by dehydration, which effects the body temperature control system towards failure. Other common symptoms of heat stroke include confusion, disorientation, nausea, seizures, loss of consciousness, coma, throbbing headache, dizziness, light headedness, and dry skin. Heartbeat may be pronounced or feeble or rapid with shallow breathing. The first aid for heat stroke patients is to shift them to a sheltered area, remove extra cloth, and not use ice for older patients, young patients, or patients with chronic diseases or patients with heat stroke that happened without exercise. Apply the ice packs to armpits, groin, neck, and back because these areas have blood vessels close to skin; if possible immerse the patient in a shower or tub of cold water. The patient should be encouraged to drink plenty of water and cool the skin by spray or sponge of cold water and fan (Glazer 2005).

8.9

Diarrhea

Diarrhea is the condition of having at least three watery loose motions or liquid bowel movements in a day. Persistent diarrhea can be treated by giving oral rehydration solution and loperamide. If diarrhea lasts for more than 2 weeks then one should see a doctor. Diarrhea can be caused by a variety of things that may not be related to a specified disease, for example excessive liquid diet, stress, anxiety,

124

A. N. Nagappa and J. Kanoujia

use of laxatives, or food allergies. In most of the cases replacement of lost fluid with an oral rehydration solution (ORS) can resolve diarrhea. Drugs like loperamide can also be useful in the management of nonspecific diarrhea (Casburn-Jones and Farthing 2004).

8.10

Constipation

Constipation refers to reduced bowel movements that are infrequent or hard to pass. The stool often gets very hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement. Common causes of constipation include dehydration, lack of dietary fiber, physical inactivity, or medication side effect. Drinking more water and increasing dietary fiber in food can help to resolve this issue; it is also important to do regular physical exercise and walking; one can also use laxative and stool softeners (Portalatin and Winstead 2012).

8.11

Eye Infections

Eye infections occur due to harmful microorganisms like bacteria, fungi, and virus. Infectious conjunctivitis, or pink eye, is one of the most common eye infections. It happens when blood vessels in the conjunctiva, the thin outermost membrane surrounding the eyeball, become infected by bacteria or virus. As a result, your eyes become pink or red and inflamed. It can also result from allergies or exposure to chemicals, like chlorine, in swimming pools. Conjunctivitis caused by bacteria or virus is extremely contagious. It can still spread up to 2 weeks after the infection starts. One should seek treatment if any of the following symptoms occur: reddish or pinkish tint in eyes, watery discharge from eyes that is thickest when one wakes up, itchiness or feeling like there is something constantly in your eyes, and producing more tears than usual, especially in only one eye. Treatment depends upon the type of conjunctivitis; for example if it is bacterial, then antibiotic eye drops, ointments, or oral medications can be used to help kill bacteria in your eyes. After starting antibiotics, symptoms fade in a couple of days. If it is viral, no treatment exists. Symptoms tend to fade after 7–10 days. Apply a clean, warm, wet cloth to your eyes to relieve discomfort, wash hands frequently, and avoid contact with others; if it is allergic, over-the-counter (OTC) antihistamines like diphenhydramine (Benadryl) or loratadine (Claritin) help relieve allergy symptoms. Antihistamines can be taken as eye drops, and anti-inflammatory eye drops can also help with symptoms. Naphazoline eye drops can help get rid of congestion in the eye to get relief from bacterial conjunctivitis; however, only redness is cured not the infection; there is no treatment for pink eye due to a viral infection. There are antibiotic eye drops for treatment of red eye, caused by bacterial infection, for example chloramphenicol eye drops and eye ointments.

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

125

Other types are infectious keratitis when cornea gets infected. Cornea is the clear layer that covers the pupil and iris. Keratitis results from either an infection (bacterial, viral, fungal, or parasitic) or an eye injury. Keratitis means swelling of the cornea and is not always infectious. Endophthalmitis is a severe inflammation of the inside of the eye resulting from a bacterial or fungal infection. Candida fungal infections are the most common cause of endophthalmitis. Blepharitis is an inflammation of eyelids, the skin folds covering eyes. This type of inflammation is usually caused by clogging of the oil glands inside the eyelid skin at the base of your eyelashes. Blepharitis may be caused by bacteria. A sty (also called a hordeolum) is a pimple-like bump that develops from an oil gland on the outer edges of eyelids. These glands can get clogged with dead skin, oils, and other matter and allow bacteria to overgrow in the gland. The resulting infection causes a sty. Uveitis happens when uvea gets inflamed from infection. Uvea is the central layer of the eyeball that transports blood to your retina—the part of the eye that transmits images to brain. Uveitis often results from immune system conditions, viral infections, or eye injuries. Uveitis does not usually cause any long-term problems, but can lead to vision loss if a severe case is not treated. Cellulitis of the eyelid, also known as periorbital or preseptal cellulitis, is an infection of tissues around the eye. The infection can be caused by a minor trauma to the area around the eye, such as an insect bite. It can also occur as a result of another infection, such as sinusitis. Cellulitis of the eyelid causes redness and painful swelling of the eyelid and the skin surrounding eyes. The condition occurs much more often in children than in adults. Ocular herpes happens when the eye is infected by the herpes simplex virus (HSV-1). It is often just called eye herpes. Eye herpes is spread by contact with someone who has an active HSV-1 infection, not through sexual contact (that is, HSV-2). One should visit an ophthalmologist for treatment of conditions described above, except conjunctivitis which a community pharmacist can treat as a minor ailment (Wood 1999; Caldwell et al. 1992).

8.12

Earache

Pain in the inner or outer ear may interfere hearing ability, which is often caused by excess fluid and infection. Common causes of ear pain include wearing a tight head ware, using poorly fitting headphones, sleeping on head surface, ear piercings, grinding teeth, or accidental insertion of a head object in the ear. Treatment usually involves compressing on the ear with a warm moist cloth. OTC anti-inflammatory drugs can help in relief of pain and discomfort. A cold pack can help in relief of pain in an earache. Sometimes garlic or onion juice in coconut oil may be useful. If there is a middle-ear infection caused by respiratory infection there can be fluid buildup behind the eardrums where bacteria can colonize and breed. In such conditions, treatment of respiratory tract infection and middle-ear infection with an antibiotic can resolve the problem (Worrall 2011).

126

8.13

A. N. Nagappa and J. Kanoujia

Hay Fever (Allergic Rhinitis)

Hay fever (allergic rhinitis) accounts for ten million cases per year. The cluster of symptoms of hay fever is a runny nose, itchy eye or mouth or skin, sneezing, congestion or stuffy nose, and fatigue. Hay fever is triggered due to outdoor allergens such as pollens from plants and indoor allergens such as pet hair or dander, dust mites, and mild irritants like cigarette smoke, diesel exhaust, or perfume. There are two types of hay fever: seasonal and perennial; seasonal hay fever symptoms can occur in spring, summer, and early fall. It is usually caused by airborne spores of mold and pollens from plants. Perennial symptoms occur throughout the year and are caused by sensitivity to dander, dust mite, cockroaches, mold, and pet hair. Management and treatment involve identifying and avoiding the allergens that trigger symptoms. Avoid using window fan that can drop pollens into the house. Wearing the sunglasses and pollen mask can prevent exposure of pollens to the eye and nose. It is also important not to hang washed cloth outside to dry. This may lead to pollens clinging to towels and cloths. Avoid rubbing the eyes which will irritate and make the symptoms worse (Solelhac and Charpin 2014). For indoor exposure of allergens one can close the windows and use the air conditioner in home and car. Checking the air conditioner for cleanliness and absence of allergens is an important precaution. In bedrooms, using bedsheets and pillows which are mite-proof and washing the bed cloths with boiling water once in a week are effective approaches to get rid of dust mite. In order to check the mold, one should keep the humidity between 30% and 50% and clean the bathroom, kitchen, and basement on a regular basis. On exposure to pets, one should wash hands and if allergic to household pets he/she should avoid exposure to animal allergens; closing of the air vents of bedrooms can help in avoiding exposure to allergens, and replacing the floor carpet with hardwood, tiles, or linoleum can provide relief. OTC medications are used in the management and control of symptoms of allergic rhinitis. Intranasal cortical steroids are sprays which can control symptoms of allergic rhinitis. Antihistamine and decongestants are for symptomatic relief. One should avoid the use of antibiotics and nasal surgery as it is not an infection nor is it a physical deformity. However, hay fever may occur due to occupation known as occupational rhinitis; in such circumstances, change in occupations is recommended.

8.14

Corns and Calluses

Corns and calluses are thick, hardened layers of skin that develop due to friction and pressure. Corns are smaller than calluses having a hard center surrounded by inflamed skin. They tend to develop on parts of feet, top and sides of the toes, and between the toes. They can be found on weight-bearing areas and can be painful when pressed. Calluses usually develop on the sole of the feet especially under the palms and knees. Calluses are not painful and are larger than corns; it happens due to the repetitive action of pressure and friction in the legs. They develop by wearing ill-fitting shoes and shoes without socks and playing instrument or using hand tools,

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

127

despite severe friction. They can be prevented by wearing correct size shoes with socks and wearing padded gloves while using hand tools. One can trim away the thickened skin or use corn caps containing 40% of salicylic acid (clear away; Mediplast corn caps) (Singh et al. 1996).

8.15

Contact Allergic Dermatitis

Contact dermatitis is a red, itchy rash caused by direct contact with a substance or an allergic reaction to it. The rash is not contagious or life threatening, but it can be very uncomfortable. Many substances can cause such reactions, including soaps, cosmetics, fragrances, jewelry, plants, poison, ivy, nickel used in cell phones, eye glass, frames, zippers and belt buckles, nail polish, latex, and cement. In order to reduce aching and soothe the inflamed skin, identifying and avoiding irritant allergen is the first step. Applying an anti-itching cream or lotion to the affected area and taking an oral anti-itching drug (antihistamine, cetirizine) can be helpful. An application of cool wet cloths and avoiding scratching can give some comfort (Nguyen and Yiannias 2019).

8.16

Cough

Cough is a sudden forceful hacking sound to release air and clear an irritation in the throat or airway. It can be due to irritants like smoking or improper swallowing of food and liquids. It may also be due to viral, bacterial, or fungal infection affecting the nose, throat, and airways. Self-treatment includes drinking liquids to clear the obstructing substances or using lozenges, cough drops, and vaporizers which may help to soothe a cough. Cough medicine may help in giving mild relief. It is better to refer to a doctor if the patient has a fever above 100
F, yellow or green phlegm, and wheezing. The condition may be serious if the patient cannot speak due to chocking and is having difficulty in breathing and swallowing, and also cases where stains of blood are found in phlegm and there are persistent night sweats, fever, and weight loss. In a dry cough phlegm is not produced, but it still exhausts the patient due to repetitive coughing. To get rid of dry cough one should drink good amount of water and drinking hot drinks like soups and menthol cough drops helps. Taking steamy shower can give a good relief. Drugs like dextromethorphan, a cough reflex suppressant, can give some relief. Making a hot drink by adding honey and swallowing slowly can be soothing to the irritated throat (Morice et al. 2006). To get rid of dry cough one can try a humidifier; decreasing the allergen in the room and managing gastroesophageal reflux disease (GERD) can give some relief. Drinking tea with honey, gargling with saltwater, and quitting smoking can help.

128

8.17

A. N. Nagappa and J. Kanoujia

Dandruff

Dandruff is a skin condition that mainly affects the scalp. It is caused due to a clump of skin cells due to oil from scalp and appears as white flakes. It can be caused by a number of things like dry skin, sensitivity to hair cosmetics, or eczema or seborrheic dermatitis. There can be an overgrowth of yeast or fungus causing dandruff. Dandruff cannot be cured but can be controlled. To reduce the shedding of dead skin cells from scalp which is a natural occurrence, one should keep the scalp wet with hair oils like coconut oil. When the scalp is deficient in oil content, it becomes dry and starts to shed as minute flakes of dead skin cells. The best way to get rid of dandruff is to use an antidandruff shampoo which reduces shedding of flakes and gives relief from itching, redness, and dry scalp (Nowicki 2006).

8.18

Dysmenorrhea (Premenstrual and Menstrual Pain)

Dysmenorrhea is the menstrual cramps which are caused by uterine contraction. Primary dysmenorrhea refers to common menstrual cramps, and secondary dysmenorrhea is due to disorder in the reproductive organs. Primary dysmenorrhea is common menstrual cramps that are recurrent and are not due to other diseases. Pain usually begins in one or 2 days before the onset of menstrual cycle often when bleeding initiates. Pain is felt in the lower abdomen, back, or thighs. Pain can be mild to severe which can last for 12–72 h. It can be accompanied by nausea, vomiting, fatigue, and diarrhea. Menstrual cramps become less painful as women age. It may stop completely if the woman has a baby. Because the symptoms are so similar, adenomyosis is often misdiagnosed as uterine fibroids. However, the two conditions are not the same. While fibroids are benign tumors growing in or on the uterine wall, adenomyosis is less of a defined mass of cells within the uterine wall or infections. Here the menstrual cramps begin earlier in menstrual cycle and last longer; pain is not accompanied by nausea, vomitting, fatigue, and diarrhea. Over-the-counter medicines such as ibuprofen, mefenamic acid, or naproxen can be used at regular doses starting the day before the menstruation begins. Treatment involves using heating pads where the pain is felt; heating pad improves blood circulation and helps in clearing accumulated pain mediators; OTC medication prevents the synthesis of pain mediators. Alternative medicines known to help patients are melatonin, vitamin E, fennel oil, dill oil, chamomile oil, cinnamon, Damask rose, rhubarb, guava, and uzara (Proctor and Farquhar 2006).

8.19

Dyspepsia (Indigestion)

Indigestion, also known as dyspepsia, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier than expected when eating. Overeating or food intolerance/taking medicines on an empty stomach

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

129

may manifest as upper abdominal discomfort described by the patient as a burning sensation, bloating, nausea, or feeling full quickly after starting to eat. Using antacids may help in relief; eating smaller meals, chewing the food thoroughly, reducing body weight, and avoiding fatty foods and carbonated beverages are long-term measures to get relief from dyspepsia. Functional and undifferentiated dyspepsia have similar treatments. Drug therapy decisions are difficult because trials include heartburn in the definition of dyspepsia. This has led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn. Traditional therapies used for this diagnosis include lifestyle modification, antacids, H2-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy (Talley and Vakil 2005).

8.20

Fungal Infections of the Skin

Fungal infections are also called mycosis; most of the fungal infections involve keeping the affected area clean and dry and applying topical antifungal drugs. Fungal infection of the skin responds to over-the-counter antifungal creams and lotions. Fungal infection happens if the immune system is weak. Over-the-counter treatment in the form of creams can be applied for yeast infections of the skin. Vaginal boric acid can be used to treat yeast infection in women. The application of tea tree oil is practiced as the traditional medicine as well as consumption of probiotic supplements, natural yogurt, coconut oil, garlic, and oregano oil (Meis and Verweij 2001).

8.21

Gastroesophageal Reflux Disease (GERD; Heartburn)

GERD is also known as acid reflux, and is a long-term condition in which stomach contents rise up into the esophagus, resulting in either symptoms or complications. Symptoms include the taste of acid in the back of the mouth, heartburn, bad breath, chest pain, vomiting, breathing problems, and wearing away of the teeth. Complications include esophagitis, esophageal stricture, and Barrett’s esophagus. Gastroesophageal reflux is a chronic condition in which stomach contents sometimes flow backward, up into the esophagus. The digestive juice from stomach which is rich in hydrochloric acid causes wound and pain in the esophagus; GERD is a more serious chronic form of reflex disorder. GERD is also called acid indigestion, acid reflex, acid regurgitation, heartburn, and reflex. GERD can interfere with daily living but most of the people get relief from lifestyle modifications, home remedies, and medical treatment. Symptoms of GERD comprise fallowing symptoms of frequent heartburn regurgitation, sore throat, and difficulty in swallowing due to feeling of a lump substance in the throat, damaged teeth, chest pain, and bad breath (Gyawali and Fass 2018).

130

A. N. Nagappa and J. Kanoujia

A number of OTC drugs are available to treat GERD and its symptoms; these are antacids (quick but mild relief), magnesium hydroxide calcium carbonate, H2 blockers (ranitidine and famotidine), proton pump inhibitors, pantoprazole, and omeprazole.

8.22

Hemorrhoids

Hemorrhoids also called as piles are a condition in which veins in the rectum are swollen and inflamed, causing discomfort and bleeding in the anus. Depending on the location they often result in unrelenting discomfort, pain itchiness, and bleeding. It may be caused due to straining during defecation or might be associated with obesity and pregnancy. High-fiber diet stool softeners like docusate sodium with several brand names are available in the market; they are also known as emollient laxatives which work by lowering the absorption of water in the intestine, thereby increasing the volume of water in the stool; this makes stool easy to pass as it is soft due to high water content. Types of over-the-counter (OTC) preparations for constipation include bulk-forming laxatives, for example, methylcellulose (Citrucel) and psyllium hydrophilic mucilloid (Metamucil); stool softeners such as Colace and Surfak; and lubricant laxatives such as mineral oil (liquid petrolatum) (Acheson and Scholefield 2008). Household remedies include ice packs to relive local inflammation and pain, and a sitz bath in which a person sits in a tub of warm water for 10–20 min to reduce itching and irritation. Epsom salts or baking soda is added to reduce inflammation. Witch hazel may decrease bleeding and prevent infection by acting as an astringent. Aloe vera gel, vitamin E oil, and coconut oil can help soothe and shrink minor external hemorrhoids. Diet should contain soluble fibers which helps in relieving constipation and preventing hemorrhoids. One can consume 25–30 g of fibers daily; excellent sources of fiber include beans, legumes, dried fruits, fresh vegetables, green peas and beans, fresh fruits (avoid bananas), prune juice, and whole grains like barley, bran, brown rice, and whole-grain bread; for pain relief one can use naproxen and ibuprofen. Hemorrhoid creams containing shark liver oil act as a natural vasodilator; it helps in reducing bleeding and pain during defecation. Rectogesic ointment containing 0.2% nitroglycerin is used to relieve pain and discomfort of mild-to-moderate hemorrhoid.

8.23

Herpes Simplex (Cold Sores)

Cold sores are also called herpes simplex; it is a viral infection caused by herpes simplex around the board of the lips; oral herpes causes tiny, fluid-filled lesion called cold sores or fever blisters which usually recur. It is easy to diagnose as the patient complains of sore lips and tingling lips with ulcers. Burning sensation, blister rashes, and red ulcers can be seen in the skin area of the lips. Nursing care is used to monitor supportive care for improvement. Medication can speed up healing and reduces

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

131

recurrence. Compressing the affected areas with cool compress helps in relieving pain in muscles and joints and helps in reducing inflammation by a soothing effect. Medication used in cold sores consists of antiviral drugs which reduce recurrence of cold sores. Antiviral drugs (docosanol or benzyl alcohol) are used as topical preparation. Lemon balm helps to reduce swelling and redness. Topical application of aloe vera gel helps in controlling inflammation and soothing. Sometimes sunscreen cream can reduce cold sore, for example, SPF-30. Prescription medicines include acyclovir, valacyclovir, famciclovir, and penciclovir (Whitley and Baines 2018).

8.24

Impetigo

Impetigo is also known as school sore; it is a highly contagious skin infection that causes red sore on the face. It mainly affects infants and children. Impetigo usually appears as a red sore on the face especially around nose and mouth and on hands and feet. The sore bursts and develops honey-colored crust. It is mostly caused by Staphylococcus aureus bacteria. Topical antibiotic ointments and creams usually clear up impetigo in 7–10 days. It can also clear on its own in 2–4 weeks without antibiotics, but there is a risk of developing complication. A home treatment comprises cleaning and soaking with warm water and soap; removal of the crusts exposes the bacteria beneath. It should be done regularly; antibiotic ointment should be applied and then the source can be covered lightly with gauze or bandage. Bathing with bleach or hypochlorite or hydrogen peroxide helps to disinfect the skin (Sahu and Mishra 2019).

8.25

Mild Acne

Mild acne is the most common minor form of acne appearing as bumps and black heads on face. They may also be papule or pustule. Mild acne is treated with topical medication such as azelaic acid, salicylic acid, or benzoyl peroxide. Topical antibiotic ointments like erythromycin, metronidazole, and clindamycin are also used to treat mild inflammatory acne. To get the best treatment for acne one should understand whether acne is mild, moderate, or severe and also recognize whether there is any inflammation in the acne (Kraft and Freiman 2011).

8.26

Mild Headache

Mild headache symptoms are not very severe and do not need immediate medical attention. Symptom of mild headache is a dull, squeezing, or band-like pain that affects both sides of the head above eyebrows. These headaches can come often and at predictable intervals; tension-type headache is the most common form of mild headache. Usually OTC pain killers like ibuprofen, aspirin, or paracetamol can give relief from mild headache. Patients should be advised to drink plenty of fluids.

132

A. N. Nagappa and J. Kanoujia

Conditions that cause mild headache include inflammation of blood vessels in and around the regions of the brain, which can occur before a stroke. It may be due to infections such as meningitis, abnormal intracranial pressure (low or high), brain tumor, or traumatic brain injury. Pharmacists should be able to distinguish mild headache from other conditions mentioned above. Usually if it is due to tension, it can be resolved by mild analgesic like aspirin or paracetamol.

8.27

Mild-to-Moderate Eczema

Eczemas are a group of skin rashes which become dry and flaky in children. In adults they are seen as scaly leathery patches which are usually itching. Initially it will be a mild and moderate itch, which is not very severe, but gradually becomes more severe and inflamed. Itching is so severe that patients continue to scratch the area until they bleed. It can appear anywhere in the body, especially in neck, inner elbow, and behind knees. Eczema is not contagious. It cannot spread to others. Its origin is either genetics or environmental factors. Eczema flares up when an irritant or allergen challenges the immune system making the skin cells to behave abnormally, leading to eczema flare-up. There is no cure for eczema; however there are treatments for patients depending on the age and severity. Treatments include OTC remedies, prescriptions of topical preparation, phototherapy, immune suppressants, and biologic drugs (Wong et al. 2017). There are also natural and alternative treatments available for the treatment of eczema. One can use moisturizing creams which helps in reducing symptoms such as rashes, redness, and itch. It may also contain medicines to prevent skin infections. Bathing is the most effective way of treatment of dry skin. One can pacify the symptoms by soaking in a warm bath and taking a shower followed immediately by moisturizing of the skin within 3 min. It can also be treated by cleaning with vinegar, salt, oatmeal, or baking soda. Skin becomes itchier when it is dry and lacks moisture which can be managed by an appropriate moisture agent. Ointments with high oil content such as petroleum jelly and mineral oil are good for treating eczema as they can calm down the skin and retain moisture of the skin by sealing. Creams are the second choice although they contain less oil but they have moisture. Lotions are primarily made of water; when applied they quickly evaporate leaving a layer of oil and sealing the moisture in the skin. Topical prescription medications include corticosteroids, PDE-4 inhibitors, topical calcineurin inhibitors, and skin barrier creams. Calcineurin inhibitors are medicines which inhibit the action of calcineurin. Calcineurin is an enzyme that activates T cells of the immune system. T cells (also called T-lymphocytes) are a type of white blood cells that play a key role in cell-mediated immunity. Phototherapy comprises exposing the skin with a special machine emitting ultraviolet rays onto the skin. This helps to reduce itching and inflammation, increase vitamin D production, and kill the bacteria. Coconut oil reduces the chance of infections by Staphylococcus aureus bacteria when applied to the skin. Sunflower oil acts as a barrier helping to retain moisture since it has antiinflammatory properties as well. Cardiospermum ointment is prepared from the plant

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

133

extract of Cardiospermum halicacabum Linn. It reduces inflammation and kills bacteria on the skin; topical vitamin B12 is also very much effective in combating the symptom of eczema.

8.28

Mild Urticaria (Hives, Bug Bites, and Stings)

Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques (wheals) on the skin that appears suddenly—either as a result of the body’s reaction to certain allergens or for unknown reasons. Hives usually cause itching, but may also burn or sting. Urticaria/hives is an outbreak marked by transient appearance of smooth slightly elevated papules or plaques that are red in color accompanied by severe pruritus. Most cases of urticaria are of short duration and self-limiting. Acute urticaria sometimes may lead to anaphylaxis or angioedema which needs immediate treatment. Drugs used for urticaria are antihistamines. Acute urticaria may be due to food allergy, drug allergy, physical contact with allergenic (occupational exposers), insect bites, and hypersensitivity to an ingested, inhaled, or percutaneous accumulation of substance, for example, latex or stinging of beehives (Yadav and Bajaj 2009).

8.29

Minor Joint Pain

First symptoms of minor joint pain and joint stiffness seem like a minor pain but if it persists one should see a doctor for an evaluation. Minor joint pain is usually insignificant which does not require any attention. Arthritis symptoms are classified as mild, moderate, and severe. Symptoms of mild arthritis could be from several different conditions like osteoarthritis, rheumatoid arthritis, gouty arthritis, systemic lupus erythematosus, and systemic sclerosis. This mandates evaluation by a doctor; patients may delay seeing a doctor thinking that symptoms are mild; they start taking self-medication with OTC painkillers. For mild osteoarthritis, paracetamol can give relief to pain. If it is not giving relief, then NSAID is recommended. There are many nondrug treatments that can be beneficial for minor arthritis pain; staying active with especially aerobic and muscle-strengthening exercise is helpful; if the patient is overweight, losing weight can reduce minor joint pain.

8.30

Minor Muscle Pain

Muscle strain is a pulled muscle that occurs when a muscle is overstretched or torn. Strain can be a cause of pain and may limit movement within the affected muscle group. Mild-to-moderate strain can be treated at home with ice, heat, and antiinflammatory medications. The affected area of the body where pain is experienced can be given rest. Taking an OTC medication and applying ice to the affected area can relieve the pain. Depending upon the cause, muscle pain can be mild, moderate, or severe; an accompanying symptom is fibromyalgia.

134

8.31

A. N. Nagappa and J. Kanoujia

Minor Sleep Disorders

Sleep deprivation is not a specific disease but usually a symptom of poor health. It is becoming more common due to sleep apnea, insomnia, narcolepsy, restless leg syndrome, aging, and psychological illnesses, like depression, stroke, and other psychosomatic disorders. Most of the people under stress suffer from sleep deprivation. Treatment for sleep deprivation is based on its severity. It is better to try non-medication treatments with home remedies, before switching to drugs. Home remedies for sleep deprivation include relaxing, taking a warm bath, or reading some book before going to bed; meditating and allowing the mind to drift peacefully to sleep can also be tried (Abad and Guilleminault 2003).

8.32

Nasal Congestion

Nasal congestion, also called as stuffy nose, is due to the accumulation of excess of fluid and mucus in the nasal passages; it may be triggered by infection, tobacco smoke, or sometimes perfume. Other causes may be due to anatomical variation leading to stacking of the object in the nose or dried mucus. Self-treatment includes using a humidifier or rinsing inside of the nose with lukewarm saline solution to provide relief from nasal congestion. If the symptoms are triggered by allergy, then it can be managed by taking antihistamines. One should see a doctor if the congestion persists for more than 10 days. If there is a greenish discharge with fever and sinus pain with blood-tinged mucus discharge, then there can be an infection. If babies younger than 2 months are having nasal congestion with fever, one should see a doctor immediately. A clear nasal discharge following head injury or any breathing difficulty warrants a serious condition (Benninger 2009).

8.33

Nausea

Nausea is an uneasy sensation with an urge to vomit. Common causes of the symptom may not be due to a disease, for example, motion sickness while traveling in car and air. Taking medicines on an empty stomach or eating too much or too little can also cause nausea. Drinking too much alcohol can lead to nausea. Self-treatment includes resting, eating bland foods, and avoiding food, perfume, smoke odors, and stuffy rooms. For traveling sickness, OTC medicines may help to relieve symptoms. One should seek medical care if feeling nausea, losing appetite for a month, and suddenly losing body weight accompanied with nausea. If one gets nausea along with chest pain, severe headache, or abdominal pain, then there can be other reasons. One should go for medical checkup in case of blurred vision, fainting, confusion, dry mouth, weakness, and infrequent urination with nausea.

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

8.34

135

Nicotine Dependence

Nicotine dependence, also called as tobacco dependence, is an addiction caused by nicotine. Here the patient cannot stop using the nicotine as it produces physical and mood-altering effects with temporary satisfaction. There is an urge to continue smoking and difficulty in leaving the habit leads to nicotine dependence. Smoking is a risk factor for many diseases like asthma, COPD, angina, peripheral vascular disease, stroke, heart attack, skin damage, infertility, erectile dysfunction, insulin resistance, premature sudden death, and cancer. Treatments for nicotine replacement therapy consist of nicotine patch, gum, lozenge, inhaler, and nasal sprays. For treating nicotine dependence there are drugs which act on nicotine receptors. For example, varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Varenicline acts by interfering with nicotine receptors in the brain and removing the pleasant sensation of smoking. Clonidine is used as a last resort for nicotine dependence; bupropion hydrochloride acts by releasing dopamine and norepinephrine. It is often prescribed along with nicotine patch (Polosa and Benowitz 2011).

8.35

Oral Fungal Infection (Thrush)

Oral fungal infection, also called as oral thrush, occurs due to yeast infection inside mouth or on tongue. This is also known as oral candidiasis or pharyngeal candidiasis. Sometimes it can be problematic due to weak immune system. Symptoms of oral thrush are occurrence of creamy white bumps on the tongue, inner cheeks, and tonsils; mild bleeding occurs when bumps are scraped. Pain at the site of bumps due to dry cracked skin at the corners of the mouth causes difficulty in swallowing. Oral thrush happens when C. albicans fungus grows out of control. People with diabetes, anemia, or HIV are at risk for oral thrush. Persons who are using dentures are likely to get oral thrush and also patients who had an organ transplant; medical treatments comprise antifungal drugs and home remedies include brushing the teeth with soft toothbrush, avoiding scrapping of lesions, cleaning the dentures, and maintaining appropriate blood sugar levels in diabetes. Use of lukewarm saltwater to rinse mouth can control oral thrush; one should mix half teaspoon of salt in eight ounces of warm water. Eating plain curd can help to restore and maintain infection under control (Elles et al. 2017).

8.36

Oral Ulcers (Canker Sores)

Mouth ulcers or oral ulcers (canker sores) develop as a small painful lesion in the mouth or base of the gums. The main symptom is the painful sore in the mouth making it difficult to eat and talk. Multiple factors can cause canker sores like injury to the mouth, acidic or spicy food, vitamin deficiency, hormones, stress, or autoimmune disorders. Most canker sores require no treatment and heal on their own. For

136

A. N. Nagappa and J. Kanoujia

relief of pain and to improve healing, one can use saltwater or baking soda for rinsing. Applying small amount of milk of magnesia on canker sores can give relief. Honey is also used to treat mouth ulcers. Drugs like ibuprofen and paracetamol can help in pain management; coconut oil can reduce swelling that causes the pain. When sores rub against the teeth unbearable pain is experienced. In order to treat cracking and dryness of lip sore, applying petroleum jelly can be useful. Apple cider vinegar helps to kill bacteria that are irritating the sore; mixing one teaspoonful of acid apple cider vinegar in one cup of water and keeping it in mouth for one minute can help (Tarakji et al. 2015).

8.37

Threadworms and Pinworms

Threadworms are also known as pinworms that are small parasitic worms that infest large intestine. The worms are white and look like small pieces of thread. A person will remain infectious for a long time as these worms lay eggs on the skin around the rectum. Home remedies include raw garlic, coconut oil, and raw carrots; they cause itching leading to intense scratching, resulting in skin infection. In order to prevent pinworms, the anus area can be washed in the morning as they lay eggs at night. This can reduce the number of pinworm eggs in the intestine. Changing of the underwear and bed linen daily reduces the number of eggs. One has to wash hands thoroughly as the eggs can enter the GIT through the anal-mouth route. Eating garlic can kill and prevent female pinworms from laying eggs. There will be disturbance of sleep, mild nausea, and itching of the anal area; when there is a severe infection one may feel loss of appetite, intermittent abdominal pain with sleeping difficulty, and weight loss. The medication for pinworm includes mebendazole (100 milligrams to be taken and repeated in 2 weeks), pyrantel pamoate (OTC medication and repeated in 2 weeks), and albendazole (400 mg repeated in 2 weeks).

8.38

Urinary Tract Infection (Uncomplicated)

Urinary tract infection is also called UTI or bladder infection. The infection can occur in any part of the urinary system like kidneys, bladder, or urethra. In UTI one may experience pelvic pain, increased urge to urinate, painful urination, and blood in the urine. In case of kidney infection, the patient may feel back pain, nausea, and vomiting with fever. Treatment through medications like penicillin and other antibiotics kills the bacteria and resolves the infection. Cranberry juice is found to be useful in controlling the UTI. One has to drink lot of water and eat foods high in vitamin C and drink less coffee and alcohol and eat less spicy food. Baking soda can act as a remedy for UTI; one has to dissolve half to one teaspoonful baking soda in water and drink on empty stomach (Rowe and Juthani-Mehta 2014).

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

8.39

137

Vaginal Candidiasis (Yeast Infection)

Candidiasis vulvovaginitis is a yeast infection of the vagina. Candidiasis in the vagina is commonly called a “vaginal yeast infection.” Other names for this infection are “vaginal candidiasis,” “vulvovaginal candidiasis,” or “candidal vaginitis.” Symptoms of vaginal candidiasis include vaginal itching or soreness, pain during sexual intercourse, pain or discomfort when urinating, and abnormal vaginal discharge. There can be an inflammation, intense itchiness, and thick and white discharge from the vagina; there can be pain in the vagina which gets intense during urination or sexual intercourse. Risk factors are pregnancy, people on birth control pill, patients with HIV, weakened immune systems, and people on antibiotics. Candida normally lives inside the body (mouth, throat gut, and vagina) and on skin without causing any problems. Treatment with antifungal medicines includes fluconazole vaginal pessary or single dose of fluconazole by mouth.

8.40

Xerophthalmia (Dry Eyes)

Xerophthalmia is a progressive eye disease caused by vitamin A deficiency. The symptom includes abnormal dryness of the conjunctiva and cornea of the eye with inflammation and ridge formation. Lack of vitamin A can dry out tear ducts and eyes; if ignored it can develop into night blindness leading to serious damage to cornea. Foods like fish liver, meat, eggs, and dairy products are rich in vitamin A. For vegetarians, green leafy vegetables, carrots, yellow and orange fruits, red palm, and carotenes are rich sources of vitamin A. Beta-carotene is an antioxidant that converts to vitamin A and plays a very important role in health. It is responsible for the red, yellow, and orange coloration of some fruits and veggies. Beta-carotenes are converted into retinol which can be a source of vitamin A (Dole et al. 2009).

8.41

Warts (Excluding Facial and Genital)

Warts are caused by viruses in the human papillomavirus (HPP) family. Warts are small hard benign growth on the skin caused by a virus. Types of warts include common flat pigmented and plantar warts; black dots in the wart are blood vessels that can lead to bleeding; most warts disappear in 1–5 years without any medical treatment. Treatments of wart include salicylic acid, duct tape, cryotherapy, surgery, laser treatment, electrocautery, photodynamic therapy, and cantharidin and antigen shots (Lipke 2006).

138

8.42

A. N. Nagappa and J. Kanoujia

Screening and Monitoring of Chronic Disease and Maintaining of Patient Profile

Diseases like diabetes, hypertension, and cancer begin in humans without any symptoms. Timely diagnosis of cancer in early stages is beneficial to treat and cure before it spreads to other parts of the body. Most of the diseases start showing early symptoms which are generally ignored by the patient. However, when the disease is highly aggravated then the patient feels the necessity of visiting a doctor. The awareness and forthright thinking about health are absent in the majority of people. Public do not pay any attention to health till they become seriously ill or fall sick. Most of the diseases can be cured if patients are diagnosed before it becomes a serious condition. Early diagnosis and treatment offer freedom from complication regarding admission to a hospital. For example, complications of diabetes like retinopathy, nephropathy, neuropathy, and diabetic foot are preventable and can be managed with diminished morbidity. Another good example is the case of cervical cancer and breast cancer, wherein patients report to the hospital in the late stage of cancer when it is very difficult to treat. There must be a system of trained professionals who are engaged in continuous screening of these diseases. The public health facility for screening can be at a community pharmacy and other healthcare facilities like primary health centers. Screening centers for chronic diseases like diabetes, hypertension, and obesity can be established in community pharmacy settings. Motivation and sensitization of public to volunteer for screening is a challenge. The public attitude towards health is at its low as many of them suffer from a myth of perfect health. Health can be perfect when one practices correct lifestyle and diet. As people are careless and least motivated to take interest in their healthcare, they continue to suffer from poor health due to sedentary lifestyle. In such situations the community pharmacist is able to provide backup and motivation. Monitoring patients to adhere to treatment and making patients responsible for their own health are among the major responsibilities of a community pharmacist. Drug-taking habits of prescribed medicines and documenting the outcome of the therapy shall be adding value to the treatment. This can only happen in inpatients; however it is very difficult to pay such keen observation for outpatients and patients on ambulatory care. Patient compliance and adherence to therapy are key to the patient’s satisfaction and outcome. Here the gap in service can be filled by community pharmacy. Community pharmacist provides the services of screening and monitoring of chronic diseases. He/she can also maintain patient data in electronic health records. The electronic health record system containing all the health-related information in the electronic format as given in Fig. 8.3 can be a good support for providing pharmaceutical care services.

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

Fig. 8.3 Diet and exercise chart

139

140

8.43

A. N. Nagappa and J. Kanoujia

Patient Profile Sheet for Pharmacy Practice

Patients can avail this service in a community pharmacy by paying a designated service fee. The form contains patient demographic details, medication history, laboratory results, and details about diet and exercise. This information helps pharmacists, doctors, and nurses to know the health status of patients and provide further health services to patients in a hospital. It is safe and error free, saves time of the doctor, and makes treatment initiation without further delay. Unless the patient himself/herself demands the electronic heath record, it cannot be shared with any other persons. However, this data needs to be shared with police, court, or any other government agencies who are in search of information as per the court directions.

8.44

Conclusion

Newer changes in the method of pharmacy functioning are challenging the existence of conventional pharmacy practice. The chain pharmacy, brand pharmacy, and e-pharmacy are offering better services to patients. Despite competition, the community pharmacy practice and services are unshaken. Personal interaction and consultation are the strong foothold of conventional community pharmacy.

References Abad VC, Guilleminault C (2003) Diagnosis and treatment of sleep disorders: a brief review for clinicians. Dialogues Clin Neurosci 5(4):371–388. https://doi.org/10.31887/DCNS.2003.5.4/ vabad AbuNaba'a Y, Basheti IA (2019) Assessing the impact of medication management review service for females diagnosed with depression and anxiety: a randomized control trial. J Eval Clin Pract 26(5):1478–1489. https://doi.org/10.1111/jep.13314 Acheson AG, Scholefield JH (2008) Management of haemorrhoids. BMJ 336(7640):380–383. https://doi.org/10.1136/bmj.39465.674745.80 Ayele AA, Mekuria AB, Tegegn HG, Gebresillassie BM, Mekonnen AB, Erku DA (2018) Management of minor ailments in a community pharmacy setting: findings from simulated visits and qualitative study in Gondar town, Ethiopia. PloS One 13(1):e0190583. https://doi.org/ 10.1371/journal.pone.0190583 Basheti IA, Qunaibi EA, AbuRuz S, Samara S, Bulatova NR (2013) Home medication reviews in a patient care experience for undergraduate pharmacy students. Am J Pharm Educ 77(8):173. https://doi.org/10.5688/ajpe778173 Benninger M (2009) Diagnosis and management of nasal congestion: the role of intranasal corticosteroids. Postgrad Med 121(1):122–131 Black E, Murphy AL, Gardner DM (2009) Community pharmacist services for people with mental illnesses: preferences, satisfaction, and stigma. Psychiatr Serv 60(8):1123–1127 Bodenheimer T, Lorig K, Holman H, Grumbach K (2002) Patient self-management of chronic disease in primary care. JAMA 288:2469–2475 Bosse N, Machado M, Mistry A (2003) Efficacy of an over-the-counter intervention follow-up program in community pharmacies. J Am Pharm Assoc 52(4):535–540

8

Community Pharmacy Services: Dispensing of Prescription, Home Medication. . .

141

Caldwell DR, Verin Hartwick-Young R, Meyer SM, Drake MW (1992) Efficacy and safety of Lodoxamide 0.1% vs. Cromolyn sodium 4% in patients with vernal keratoconjunctivitis. Amer J Ophthalmol 113:632–637 Casburn-Jones AC, Farthing MJ (2004) Management of infectious diarrhoea. Gut 53(2):296–305. https://doi.org/10.1136/gut.2003.022103 Dole K, Gilbert C, Deshpande M, Khandekar R (2009) Prevalence and determinants of xerophthalmia in preschool children in urban slums, Pune, India—a preliminary assessment. Ophthalmic Epidemiol 16(1):8–14 Elles DR, Karki N, Marshall MW (2017) Oral fungal infections: diagnosis and management. Dent Clin N Am 61(2):319–349 Gammie T, Vogler S, Babar Z-U-D (2016) Economic evaluation of hospital and community pharmacy services. Ann Pharmacother 51:54–65. https://doi.org/10.1177/1060028016667741 Gilbert AL, Roughead EE, Beilby J, Mott K, Barratt JD (2002) Collaborative medication management services: improving patient care. Med J Aust 177:189–192 Glazer JL (2005) Management of heatstroke and heat exhaustion. Am Fam Physician 71(11): 2133–2140 Gregory PM, Malka ES, Kostis JB, Wilson AC, Arora JK, Rhoads GG (2000) Impact of geographic proximity to cardiac revascularization services on service utilization. Med Care 38(1):45–57 Gyawali CP, Fass R (2018 Jan) Management of Gastroesophageal Reflux Disease. Gastroenterology 154(2):302–318 Hammond T, Clatworthy J, Horne R (2004) Patients’ use of GP and community pharmacists in minor illness: a cross-sectional questionnaire-based study. Fam Pract 21:146–149 Kraft J, Freiman A (2011) Management of acne. Can Med Assoc J 183(7):E430–E435. https://doi. org/10.1503/cmaj.090374 Lau E, Dolovich LR (2005) Drug-related problems in elderly general practice patients receiving pharmaceutical care. Int J Pharm Pract 13:165–177 Law MR, Dijkstra A, Douillard JA, Morgan SG (2011) Geographic accessibility of community pharmacies in Ontario. Health Policy 6(3):36–46. https://doi.org/10.12927/hcpol.2011.22097 Lindley C, Mackowiak J (1985 Jan) Methods of inventory control. Am J Hosp Pharm 42(1): 122–128 Lipke MM (2006) An armamentarium of wart treatments. Clin Med Res 4(4):273–293. https://doi. org/10.3121/cmr.4.4.273 Mathew EM, Rajiah K, Sharma KK (2013) Consumer's perception on design and layout of consumer medical information leaflets on obesity and lipid lowering drugs. J Clin Diagn Res 7(12):2800–2802. https://doi.org/10.7860/JCDR/2013/6468.3762 Meis JF, Verweij PE (2001) Current management of fungal infections. Drugs 61(Suppl 1):13–25 Melton BL, Lai Z (2017) Review of community pharmacy services: what is being performed, and where are the opportunities for improvement? Integr Pharm Res Pract 6:79–89. https://doi.org/ 10.2147/IPRP.S107612 Morice AH, McGarvey L, Pavord I, British Thoracic Society Cough Guideline Group (2006) Recommendations for the management of cough in adults. Thorax 61(Suppl 1):i1–i24. https:// doi.org/10.1136/thx.2006.065144 Murphy J, Yemen S (1986) Computer-assisted inventory control utilizing ABC inventory analysis and EOQ in a hospital pharmacy. Can J Hosp Pharm 39(6):159–163 Negru DS, Diaconescu M, Petculescu AM, Bild V (2010) Community pharmacy--ideal location to screen and monitor hypertensive patients. Rev Med Chir Soc Med Nat Iasi 114(3):904–909 Nguyen HL, Yiannias JA (2019) Contact dermatitis to medications and skin products. Clin Rev Allergy Immunol 56(1):41–59 Nowicki R (2006) Współczesne leczenie łupiezu [Modern management of dandruff]. Pol Merkur Lekarski 20(115):121–124. Polish Papastergiou J, Zervas J, Li W, Rajan A (2013) Home medication reviews by community pharmacists: reaching out to homebound patients. Can Pharm J 146(3):139–142. https://doi. org/10.1177/1715163513487830

142

A. N. Nagappa and J. Kanoujia

Polosa R, Benowitz NL (2011) Treatment of nicotine addiction: present therapeutic options and pipeline developments. Trends Pharmacol Sci 32(5):281–289. https://doi.org/10.1016/j.tips. 2010.12.008 Portalatin M, Winstead N (2012) Medical management of constipation. Clin Colon Rectal Surg 25(1):12–19. https://doi.org/10.1055/s-0032-1301754 Proctor M, Farquhar C (2006) Diagnosis and management of dysmenorrhoea. BMJ 332(7550): 1134–1138. https://doi.org/10.1136/bmj.332.7550.1134 Rowe TA, Juthani-Mehta M (2014) Diagnosis and management of urinary tract infection in older adults. Infect Dis Clin North Am 28(1):75–89. https://doi.org/10.1016/j.idc.2013.10.004 Sahu JK, Mishra AK (2019) Ozenoxacin: a novel drug discovery for the treatment of impetigo. Curr Drug Discov Technol 16(3):259–264 Singh D, Bentley G, Trevino SG (1996) Callosities, corns, and calluses. BMJ 312(7043): 1403–1406 Solelhac G, Charpin D (2014) Management of allergic rhinitis. F1000 Prime Rep 6:94. https://doi. org/10.12703/P6-94 Talley NJ, Vakil N (2005) Practice parameters Committee of the American College of gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol 100:2324–2337 Tarakji B, Gazal G, Al-Maweri SA, Azzeghaiby SN, Alaizari N (2015) Guideline for the diagnosis and treatment of recurrent aphthous stomatitis for dental practitioners. J Int Oral Health 7(5): 74–80 Urbonas G, Kubilienė L, Kubilius R et al (2015) Assessing the effects of pharmacists’ perceived organizational support, organizational commitment and turnover intention on provision of medication information at community pharmacies in Lithuania: a structural equation modeling approach. BMC Health Serv Res 15:82 Van Der Wal MHL, Jaarsma T, Moser DK, Veeger NJGM, Van Gilst WH, Van Veldhuisen DJ (2006) Compliance in heart failure patients: the importance of knowledge and beliefs. Eur Heart J 27:434–440 Welle-Nilsen LK, Morken T, Hunskaar S, Granas AG (2011) Minor ailments in out-of-hours primary care: an observational study. Scand J Prim Health Care 29(1):39–44. https://doi.org/ 10.3109/02813432.2010.545209 Whitley R, Baines J (2018) Clinical management of herpes simplex virus infections: past, present, and future. F1000Res 7:1726. https://doi.org/10.12688/f1000research.16157.1 Whittington Z, Cantrill J, Hassell K et al (2001) Community pharmacy management of minor conditions – the “care at the chemist” scheme. Pharm J 266:425–428 Wiśniewski M, Religioni U, Merks P (2020) Community pharmacies in Poland-the journey from a deregulated to a strictly regulated market. Int J Environ Res Public Health 17(23):8751. https:// doi.org/10.3390/ijerph17238751 Wong I, Tsuyuki RT, Cresswell-Melville A, Doiron P, Drucker AM (2017) Guidelines for the management of atopic dermatitis (eczema) for pharmacists. Can Pharm J 150(5):285–297. https://doi.org/10.1177/1715163517710958 Wood M (1999) Conjunctivitis: diagnosis and management. Commun Eye Health 12(30):19–20 World Health Organization (2019) The legal and regulatory framework for community pharmacies in the WHO European region. WHO Regional Office for Europe, Copenhagen Worrall G (2011) Acute earache. Can Fam Physician 57(9):1019–e322 Yadav S, Bajaj AK (2009) Management of difficult urticaria. Indian J Dermatol 54(3):275–279. https://doi.org/10.4103/0019-5154.55641

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription, Extempore Preparation, Nuclear Medicine, Narcotic Drug Storage and Dispensing A. N. Nagappa and Jovita Kanoujia

Abstract

Hospital pharmacy services came into prominence due to necessity of big multibedded hospital with super specialty operations. The teaching hospital, corporate hospital with multiple services, has its unique requirements which cannot be met by pharmacies outside the hospital. The hospital pharmacy services also includes supply of anticancer drugs, nuclear medicine along with narcotics the steady treatment. One of the important services managed by the hospital pharmacy is ward pharmacy and satellite pharmacy. The hospital pharmacy plays an important role in the economy of hospital as it is one of the major avenues of earning profit for the hospital. Keywords

Extempore formulations · Drugs and therapeutic committee · Inventory management · Hospital formulary · Ward pharmacy and satellite pharmacy

9.1

Hospital Pharmacy Services

Hospital pharmacy service is available within premises of hospital. They are in charge for providing medications for treatments ordered by the doctors for inpatients. Hospital pharmacies closely work with hospital administrations and provide proper inputs of medicine requirement for inpatient treatment. Based on the suggestions of the hospital pharmacy, hospital administration forms the procurement policy and builds up the buffer stocks of medicines. Hospital pharmacies are different from community pharmacy in terms that they don’t have to sell medicines A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_9

143

144

A. N. Nagappa and J. Kanoujia

for the public like in community pharmacies. They are the employees of the hospital. Their main job is to provide the medicines to the nurses based on the medication order written by the doctors. They must control inventory of medicine and provide logistic support for therapeutic team. They are also involved in dispensing the drugs and have to stand by all the drug-related laws. The regulatory bodies ensure the appropriate management of drugs in the hospital by conducting inspections. They have to assure that all the regulations, terms and conditions stated in the license are followed and the administration of hospital pharmacy is under the supervision of a registered pharmacist. Hospital pharmacy is an institutional pharmacy unlike community pharmacy which is a business organization (Abousheishaa et al. 2020). The hospital pharmacy supplies the demand for medicines by central pharmacy, satellite pharmacy, ward pharmacy and nuclear pharmacy. Hospital pharmacies have to supply medicine to the nurses on indent of prescription. The central pharmacy is headed by chief pharmacist. The chief pharmacist has to organize the activities in pharmacy to ensure steady supply of medicines for inpatients. Chief pharmacist should maintain good inventory of all the medicines required in the hospital. Pharmacists are also involved in maintaining the stock register, managing the expiry register on daily basis. The supply of medicines to intensive care unit (ICU) is directly from the pharmacy, and medicines for non-ICU patients need to be bought by the patient or patient’s attender and given to the nurses for administration purpose. For this sake, central pharmacy also runs drugstore, wherein registered pharmacist is engaged in dispensing of medicine written in prescription by the doctors. Drugstore also provides medicine for discharge patients wherein hospital pharmacist is supposed to engage in discharge medication counselling. He may also ask the help of clinical pharmacist to provide medication counselling for the patients getting discharged from the hospital. In order to bring pharmacy near the patients and nurses, hospital pharmacy may also create a satellite pharmacy. Satellite pharmacy is an extension of central pharmacy established to help patients and nurses to get the supply of medicines near their wards. It is also going to reduce the rush of crowd in central pharmacy. Ward pharmacy is a part and can also parcel the medicines for emergency wards, trauma centre and ICU. Here the ready stocks of essential medicine are kept for immediate use. In ward pharmacy, although pharmacist is responsible for dispensing, there is no need of pharmacist being engaged in dispensing. The pharmacist has to visit the ward pharmacy and check the stock of unutilized medicine and fill the stock with utilized medicine from time to time (preferably morning, afternoon and night). The pharmacist can also be called to supply medicine if demanded by nursing staff and doctors. Hospital pharmacy is supposed to handle huge quantities of variety of medicines every day. These medicines are to be allocated to the intensive care units as well as wards as per the inpatients’ medication protocols. Bigger hospitals may adopt automated pneumatic transport system to help the efficient distribution of medications. The hospital pharmacy is also accountable to provide sterile medications which are manufactured in the licensed unit of hospital. They can manufacture IV fluids and reconstituted sterile injections to be used for inpatients only. They also undertake the manufacture of bulk ointments and liquid orals.

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

145

Hospital pharmacy should apply and obtain license for compounding or manufacturing of medicine. For example, they are supposed to compound medicines and prepare neonatal antibiotics and chemotherapy (Morecroft et al. 2015; Gould et al. 2013). It is also the work of hospital pharmacy to prepare and supply neonatal antibiotic injections and intravenous formulations which have to be prepared on the request of doctor/nurse in the hospital. This is a complex task requiring specialized training of personals, quality assurance and appropriate facilities with skills of manufacturing. Some hospitals or pharmacies outsource the services to other nearby compounding pharmacy. Nuclear pharmacy is a part of hospital pharmacy engaged in dispensing of radiopharmaceuticals. Many hospitals are outsourcing the management of nuclear pharmacy which is having a risk of radiotoxicity for the pharmacist engaged in running of the pharmacy. The radiotherapeutic and radiodiagnostic handling can cause occupational hazard to pharmacists. Cytotoxic drugs are hazardous toxic chemicals that need special care while handling the medicines. Pharmaceutical compounding is another service provided by hospital pharmacies. It involves the preparation of particular pharmaceutical product as per the customization of a patient. While preparing such pharmaceutical product, pharmacist should take necessary precautions not to add unnecessary flavours or additives which aim to alter the taste or texture. However the purpose of compounding is to make medicines more suitable to a particular patients considering patient requirement. In order to meet patient needs, pharmacist can compund the tailor-made formulation without allergic substance to avoid sideeffects. Bulk formulations like disinfectants, hand sanitizers and surgical spirits are the daily requirements of the hospital. These preparations are for hospital use only and are not for sale for the public as per the conditions laid in the license for hospital pharmacy (Watson et al. 2021). Hospital administrator (Fig. 9.1) controls the operating of hospital pharmacy and empowers the chief pharmacist to establish and manage the hospital pharmacy department. He/she establishes the Department of Pharmacy which has three major service areas in the hospital. Professional and clinical services are headed by professional clinical pharmacist. Professional and clinical services again catergorized in nuclear pharmacy, ambulatory care, unit dose dispensing, home care services, IV administrable division, and sterile products division. The educational and technical services involve the drug information and poison control services provided by specialists. The pharmaceutical and clinical research division engages in assay and quality control activities. Professional services provided by pharmacists attributed to their skills and knowledge to take an active role in patient health, through effective interaction with both patients and other health professionals. Pharmacists provide patient care in their practice optimizing therapy outcomes, as well as promoting health, wellness and disease prevention. The concept of clinical pharmacy is important for pharmacists as they deal with patients. Community pharmacists usually serve ambulatory patients, and institutional pharmacists care for both ambulatory and inpatients. Pharmacists provide extended clinical services such as assessment of health status,

146

A. N. Nagappa and J. Kanoujia

Fig. 9.1 Organization of hospital pharmacy

drug information, independent or supplementary prescribing and administration of certain vaccines. Pharmacists extend their cognitive services to other healthcare professionals in terms of providing drug information or pharmacotherapy services. To address these expanding practice responsibilities, pharmacy education must keep up with and achieve advanced educational outcomes. Nuclear pharmacy service (NPS) involves establishing a pharmacy exclusively for stocking, compounding and dispensing of radioactive pharmaceuticals and cytotoxic anticancer drugs, which are used in cancer chemotherapy and

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

147

radiodiagnostic. The nuclear pharmacy is located in the vicinity of the cancer wards. The nuclear medicines and cytotoxic dugs are having high potential to cause cancer to pharmacist engaged with radiopharmaceuticals. The individual pharmacist should be periodically assessed for exposure. If the exposure limit exceeds the safety limit, immediately another pharmacist should replace the one who is exposed to radiation above safety limit. The pharmacist working should wear appropriate metallic aprons which protect them from exposure to harmful radiations. The use of robots in handling of radiopharmaceuticals and cytotoxic agents is desirable as it protects pharmacist from injuries by exposure to radioactive drugs and cytotoxic drugs. The pharmacist should also alert the public not to frequent the nuclear pharmacy as it can destruct their health. They should follow the regimens and doses of nuclear medicines, and in case of enquiry, they should be able to answer in a professional manner (Saha 1984).

9.2

Unit Dose Dispensing (UDD)

The unit dose dispensing system is used for medication distribution. It is the method of controlling and dispensing of medications in healthcare settings. Advantages of unit dose drug dispensing involve reduction in the occurrence of medication errors. It also decreases the total cost of medication-related activities. UDD helps in generating more accurate patient billings for drugs. Studies indicate that unit dose systems are more safe, economical and efficient for the patient as compared to other drug distribution methods. A unit dose (unit-of-use) drug distribution system is in place for all dosage forms to provide patient-specific, individually packaged medications, which minimize nurse/caregiver drug product manipulation (e.g., cutting in half) in order to arrive at the correct dose prior to administration. Such manipulation could result in less patient harm and consume valuable caregiver resources. These unit doses of medication are also dispensed with individually labelled bar code packaging to enable nurse scanning of the medication at the bedside just prior to medication administration (Aldhwaihi et al. 2016).

9.2.1

Ambulatory Care and Home Care

Increased hospitalization costs and length of stay in hospitals seem to be very expensive and cause large discomfort to the patient. If patient after stabilization in the hospital wants to get treated at home, then such type of care is called ambulatory care or home care. In ambulatory care or home care services, medical care is provided on an outpatient basis which includes observation, diagnosis, treatment, consultation, rehabilitation and intervention services. This care can be combined with advanced medical technology with pharmaceutical care. The pharmacist who is designated by the hospital needs to visit the patient at their home and provides the pharmaceutical care. He/she checks the prescription and interacts with the patient to

148

A. N. Nagappa and J. Kanoujia

learn about outcomes of current therapy. Further pharmacists ask regarding the problems of the patient due to disease or medication. He documents the patient conditions and saves in the hospital records for further reference and treatment (Goodrich and Gorry 1980).

9.2.2

Intravenous Admixtures

Intravenous admixtures are combination of one or more sterile products added to an IV fluid for administration. Intravenous admixtures must be sterile and free from pyrogens since it will be directly administered into the body. Aseptic technique is a must to prepare the mixed intravenous admixture products. The preparation of parenteral admixture usually involves the addition of one or more drugs to large volume solutions such as intravenous and nutrient fluids. Premixed IV admixtures offer the advantages of preparation time savings, assurance of properly reconstituted drugs, lengthy expiration dating and appropriate labelling. However, not all drugs will be available in the form of IV solution. Hospitals may be forced to use several types of IV containers and administration sets (Plumridge and Maher 1993).

9.2.3

Sterile Product Production Unit

All medicines are not available in the market as per the need of patients. There is a requirement for making customized medicine for a patient. In hospital pharmacy, hospital pharmacists and trained pharmacy technicians compound sterile products for patients such as total parenteral nutrition and other medications given intravenously such as neonatal antibiotics and chemotherapy. This complex process requires specialized trained personnel to do quality assurance of products with appropriate facilities. Some hospital pharmacies simply outsource high-risk preparations, and some others involve the companies that specialize in compounding of high-risk formulations. For meeting this demand, sterile product production units are functional as a part of hospital pharmacy (Liu and Wosinska 2017).

9.2.4

Medication Administration

Pharmacists are involved in the administration of medications across hospital settings. Nurses are also involved in both the dispensing and preparation of medications (in a similar way as pharmacists do), such as crushing pills and drawing up a measured amount for injections. Apart from nurses, physicians, patients, certified medication technicians and family members also involved in administration

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

149

of medications. The “rights” of medication administration include right patient, right drug, right time, right route and right dose. 1. Clinical pharmacy services Hospital pharmacists are specialists in the field of drugs and actively participated in patient care by viable utilization of designated assets at the hospital level. They work closely with nursing and medical staff to make sure hospital patients receive the best treatment, advising on the dose selection and type of administration. They provide compliance aids, influenza vaccinations, prescription check, compounding prescriptions, smoking cessation support, medication delivery and renewing a prescription. Meds-to-Beds is a free service that offers education about medication and delivers prescriptions and over-the-counter medications to patients before they leave the hospital. The Anticoagulation Case Management Service (ACMS) provides anticoagulation care to patients that have established primary care with a physician provider. Patients that have been referred to the pain management clinic have the benefit of working with providers in a teambased setting. The pharmacotherapy clinic specializes in the care and management of diabetes, high blood pressure and high cholesterol. Pharmacists in this clinic work with patients more intensively in between physician visits to more closely manage these illnesses in addition to providing patient education (Hawksworth and Chrystyn 1998). 2. Educational and technical service The hospital pharmacy being a part of the hospital is responsible for development of skilled human resources for better outcome of treatments provided in the hospital. One cannot expect a nurse or doctor being proficient in pharmacy. Even the paramedical staff doesn’t have the practical knowledge about handling and administering the medicines. Hospital pharmacy should take up the responsibility of providing precise information about drugs, as this would sensitize the staff to acquire the required knowledge which they can use during the practice. They should be ready with pre-prepared educational modules which can be used to update the knowledge of doctors and nurses. Medication error is due to improper knowledge of doctors and nurses, who try to acquire the knowledge by medical representative of a pharmaceutical manufacturer. Pharmaceutical manufacturers are accused of providing incomplete information about medicine. Hence, the hospital pharmacist should always be ready with latest information for the practice of medicine. The pharmacy devices are used in the hospital for various activities like administration of drugs to patients. For example, use of metered dose inhalers for treatment of asthma. The hospital pharmacist should be able to resolve any technical issues regarding drugs and formulations in hospitals. 3. Drug information and poison control service division There are many enquires that are raised by the hospital staff, doctors, nurses, students and patients about drugs, dose and its administration. The enquiry may be oral during ward rounds, telephonic from ICU and written format. Enquiry may be initiated through what App or SMS message. It is important to document all the enquiries and make a database and archive the enquiry. If the enquiry is

150

A. N. Nagappa and J. Kanoujia

from ICU or emergency ward, it should be given the highest priority. The doctors and nurse are making decisions based on the content of the information provided. Hence, the drug information scientist who has worked in DIC can figure out and comprehend the information so that doctors or nurse is able to use the information. Nowadays many people consume poison in fit of depression. Their condition is very serious, as they would have consumed poison with an intention to commit suicide. When the patient is brought to the hospital, doctors and nurses become busy in restoring the vital parameters of life. They also want to establish the poison the patient has consumed. They may require a healthcare professional who can recognize the poison consumed by the patient. Then after establishing the poison consumed, the doctor may be interested to learn what the specific antidotes for the consumed poison. For answering such questions precisely, pharmacist should be trained and skilful as the information provided can be a matter of life and death for the patient (Hahn and Poison Control Centers 2009). 4. Education and training division The education and training division should be headed by a senior pharmacist. In hospital pharmacy, pharmacist should be ready to provide services that are demanded from the doctors in various aspects of the medicine. Pharmacists are accountable for dispensing prescription medicines to patients in the proper doses explaining how and when to use these medications. There may also deliberate possible drug, drug/food interactions with patients to ensure they use the prescription responsibly. At many pharmacies, pharmacists are also empowered to give advice on minor ailments and treat them with over-the-counter medicines. Pharmacists might also offer help to patients on nutrition, exercise, stress management and other general health issues. The pharmacy profession is ever changing. The hospital pharmacy is responsible for providing continuous education program and evaluates the performance of pharmacist on the basis of how much the patients have been able to apply newly learned knowledge. The pharmacists should have access to the journals, books and databases available on the Internet. The continuous update of the knowledge is very much important for providing quality of services which is related to outcomes of treatments (Chaghari et al. 2017). 5. Professional staff development (PSD) The competency of hospital pharmacy staff is very critical to provide quality services as per the expectations of fellow healthcare professionals and peers. Reinforcing professional ethics and motivating the staff for dedicated services is a requirement for hospital. The PSD should significantly include development of communication skills, training to handle patient enquires, apart from compounding and dispensing. There should be a separate budget allocation reserved for professional staff development program. These programs should be conducted after assessing the need and should be made compulsory for all pharmacists to undergo. It is better to link the participation of PSD with performance appraisal (Gesme et al. 2010).

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

151

6. Residency training program Hospital pharmacy is also involved to train the new pharmacist with appropriate skills available continuously for services. Many hospitals have established residency training program division, in which they engage the interns to learn the basic services and skills under the supervision of a registered pharmacist. The programs should be structured in such a way that the interns expose to all major department of the hospital. The intern gets confidence and practices the skills and knowledge acquired during his/her pre-residency education. The residency is supervised by the senior pharmacist, who corrects the interns and alerts them regarding common mistakes that happen during the routine practice. Residency is an intermediate stage in between the student and professional. During residency, the intern gets an opportunity to observe the professional practice very closely and acquires the knowledge and skill to become confident independent practitioners. The residency programs undergo rotation in order to cover entire departments of the hospital in view to expose entire gambit of professional practice (Barajaz and Turner 2016). 7. Computerized pharmacy operation division • Pharmaceutical and clinical research division: The corporate hospitals, teaching hospitals and hospitals of particular disease like cardiac, renal and cancer hospitals have the responsibility to conduct clinical trials which are important for drug development and new drug approvals. The hospitals usually have established their own pharmaceutical and clinical research division. They are also supposed to run a pharmacovigilance centre in hospitals. The role of pharmaceutical and clinical research division is to accept the clinical trial order from pharmaceutical industry and conduct them as per the approved protocol from human’s ethics committee. The logistics, recruiting the volunteers and establishing the laboratory infrastructure are the responsibility of the pharmaceutical and clinical research division (Holm et al. 2015). • Drug kinetics and bioavailability laboratory: In the treatments of critically ill patients admitted in ICU, IICU and cancer ward where dosing of patient plays a critical role, it is important to measure the plasma concentration of the drug and inform the therapeutic team for dose calculation. As per plasma concentration drug report, the doctors can decide about when to administer the next dose and how much dose has to administer. The study of live kinetics data is important which acts as guide for patient safety and efficacy of the therapy. Therapeutic drug monitoring (TDR) is finding the live concentration of plasma concentration of drugs at designated intervals in order to monitor patient condition. Depending on live concentrations, the drug may manifest toxicity or efficacy or no action. TDR plays an important role in clinics as the decisions regarding dosing and monitoring of ADR/toxicity depend on the live plasma concentrations. Some drugs require TDM as they have narrow therapeutic index like digitalis glycosides. Drugs like phenytoin or lithium may cause toxicity depending on plasma concentration. The indications for drug monitoring have widened to include efficacy, compliance, drug-drug interactions,

152

A. N. Nagappa and J. Kanoujia

toxicity avoidance and therapy cessation monitoring. All these services are provided by drug kinetics and bioavailability laboratory. • Purchasing and inventory control division: The financial management is very much important in any corporate or teaching hospitals. The pharmacy involves large number of products of various prices and requirements. There may be drug shortages in the market. It is very much essential to provide steady supply of medicines 24X7. The medicines are usually having date of expiry between 2 and 3 years from the date of manufacture. Keeping with the above conditions, pharmacist/staff should be able to initiate a program. The full participation with computer software is needed to manage purchasing and inventory control. Any disruption in the functioning of purchasing and inventory control can cause disarray in total hospital services. Purchasing and inventory control division is the lifeline of the hospital (Berger et al. 2007; Lamarre et al. 2009). • Departmental service division: The aim of this service division in pharmacy is to plan and coordinate departmental activities (out- and inpatients), develop policies (e.g., narcotics records can be kept for 1–3 years), schedule personnel and provide supervision (rotation and holidays), coordinate administrative needs of the pharmacy and therapeutics committee (selection of drug essential list for each hospital department according to needs) and supervise departmental office staff (laboratory boy, technicians and clerks). The departmental services of hospital pharmacy include filling all the medical orders with in stipulated time for the whole hospital. The pharmacist in the service division should be ready to make drug baskets of individual prescriptions and also ward pharmacy. They have to also engage simultaneously in the billing process as the patient or his/her attendants need to be informed regarding the total amount spent on the patients on daily basis. • Investigational drug study division: Investigational drug study division is also known as pharmaceutical research division. Investigational drug study division is to cooperate with the medical research staff of projects involving drugs. It also involves inpatient service division which provides medications for all inpatients of the hospital on a 24-h per day basis (rotation system). This division should have trained skilled professionals who are able to address the needs of clinical research and well equipped with knowledge about protocols of investigational drug study requirements such as formulation and plasma concentration measurements. They must be also well versed with bioavailability studies.

9.2.5

Ward Pharmacy Services

Ward pharmacy services include patients’ drug supply and therapy for inpatients in a hospital; the clinical pharmacist is supposed to visit each ward and each patient once in a day. In the ward round, the pharmacist gets an opportunity to have dialog with

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

153

the patient and involve in the clinical care. Pharmacist makes his/her own clinical notes and shares the information with the doctors and nurses and also with the patient to make the treatment simple and easy. The pharmacist should check patient’s drug therapy in their daily visit to ensure the timely taking of medicines by the patient as per the prescription, pharmacist must also monitor drug charts for miss doses, supply issues, omissions of medicines and reinforce important instructions again each medicine. Other services include dispensing services by preparing the medication for the inpatients and some outpatients and patient being discharged from the hospital. They provide a check on all medicines by talking to doctors and nurse to ensure the safe and effective use of medicines; prescription is checked for their appropriateness in turns of therapeutic utility, dose frequency and duration of treatment. Drug in-charge for in-patients can advise the doctor to amend the prescription to meet the needs of the patient. Pharmacist should follow the change in the drug therapy and provide medicine supply as per the updates in the prescription. Pharmacist also should check missed doses, lapsed supply and omission and endorses important instructions against each medicine prescribed regarding appropriate administrations. Patient counselling and how to use medication especially at the discharge stage and the final counselling are important to ensure safety and quality use of medicines [1819].

9.2.6

Clinical Trials

Pharmacists are also supposed to participate in the ongoing clinical trials in the hospital; all trial protocols are assessed by the local research ethic committee to ensure that trials shall be harmless and will improve the knowledge about the medicines. The pharmacist being a staff of the hospital is supposed to participate as an expert in medicines and give the inputs require by the local research ethic committee. They can also review the protocol and check the medicine doses, and the pharmacist should closely observed reactions of the patients to drugs while participating in the clinical trials. They should also take the responsibility of supply of medicines and dispensing during clinical trials. The drug assay and establishment of PK/PD parameter, bioavailability and first pass effect, rate of elimination from liver and kidney to be determined in clinical trial.

9.2.7

Compounding and Extempore Preparations

Dispensing and compounding were the primary responsibility of the pharmacist since oriental times. The medicines started to be available due to the discovery of new molecules, and these new molecules were basic drugs which cannot be consumed as such they need to be formulated as tablets, capsules, mixtures and ointments. The medicines are also having obnoxious taste, flavour and other organoleptic properties. In many instances, they are required on very small quantities, so

154

A. N. Nagappa and J. Kanoujia

in order to make them suitable for administration, one should overcome the above properties so that the patient can be administered with the drugs. The calculations of doses were also a major challenge, initially drugs were made extemporaneous such as powder dosage form in which several pharmaceutical aids were added. In powders, several pharmaceutical aids were added. For example, in order to increase the bulk of the powder inert substances like lactose or calcium powder were used; further handmade tablet, triturates, and capsules were prepared. Many medicines were also administered in the liquid dose form using purify water to dissolve drugs; the act of making a suitable medicine for consumption with an active pharmaceutical ingredient into dose form is called compounding (Falconer and Steadman 2017). The nick name compounder was given to pharmacist who becomes expert in making medicines suitable for consumption using active pharmaceutical ingredient. Rapid industrialization and manufacturing of unit doses forms has led pharmacist to the giving up of compounding. However, despite the availability of unit doses forms, there were a series of drawbacks in the medicines: the one cap fits all takes away the freedom to calculate dose for an individual patient and administer, some medicines need to be prepared fresh just before consumption, and due to the aforementioned reasons the compounding of medicines is again set for comeback in the practice. The patient centric care is one of the major reasons for reviving the compounding and making the medicines suitable for an individual patient. Pharmacy compounding is the art and science of preparing personalized medications for patients. Compounded medications are made based on doctor’s prescription in which individual medicines are mixed together in order to have exact strength and dose form required by the patient. The common reason for compounding drugs is to provide a form and method of delivery that will work for a particular patient. For example, young children and senior patients may have difficulty in swallowing the tablets and capsules. Similarly some people are unable to take oral medicines due to disturbance in absorption; in such cases, administering the drug in the form of suppository or transdermal gel is preferred. Compounding is also used to reduce the pill burden by combining two or three medicines together into a dose form. Some patients may be allergic and intolerance to the contents of the tablet. For example, tartrazine and lactose may have problems if the dosage form has made with these two ingredients. In such patients, one can prepare the medicines without allergic or intolerance substance. It can also be useful when company stops making particular formulation due to change in the market situation or due to lack of profit. Extemporaneous compounding is done on the prescription of an individual doctor seeking a drug that is otherwise unavailable in the market (Marriott et al. 2016).

9.2.8

Nuclear Pharmacy

Nuclear pharmacy is a branch specially involved in the application of radioactive substance in diagnosis and treatment of disease. Nuclear pharmacy is also known as radiopharmacy. It generally involves the practice of combining radionuclide label

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

155

with a pharmaceutical component to determine the localization of the drug in a patient. Radiopharmaceuticals act as prodrugs which need to be activated to have a therapeutic effect. The radiopharmaceutical carries an occupational risk for the pharmacist due to exposure to radiations. Due to their risk, nuclear pharmacy is heavily regulated to protect unnecessary exposure to the patient and staff. Most of the diagnostic investigations in radiopharmacy are performed by using technetium99 m. Therapeutic nuclear medicine is commonly used in the treatment of hyperthyroidism and thyroid cancer as well as treatment of many other cancers (Callahan 1996).

9.2.9

Narcotic Drug Storage and Dispensing

Narcotic drugs and psychotropic substances are the therapeutic agent and also abused for recreational purposes. As these drugs are highly regulated, their availability is restricted due to some of the antisocial elements and terror groups. These groups are misusing the narcotic and psychotropic substances illegally by supplying the drugs to youths and college students. They do it so, because a lot of money can be earn very easily. Despite of very heavy corporate punishment, the criminal still engages in the protection, procurement, distributions and sale of these drugs to the public and large clandestinely although it is illegal to do so. Danger of these narcotic drugs and psychotropic substances has spread its tentacles across the world; however in order to have a strict control over the drugs syndicate International Narcotics Control Board (INCB) has taken several strict steps (Bazhan et al. 1988). INCB is the independent and quasi-judicial monitoring body. It involves in the implementation of rules governed by the United Nations international drug control conventions. It was established in 1968 in accordance with the Single Convention on Narcotic Drugs, 1961. In India, the Narcotic Drugs and Psychotropic Substances Act, 1985, commonly referred to as the NDPS Act, is an act passed by the Parliament of India that prohibits a person to produce/manufacture/cultivate, possess, sell, purchase, transport, store and/or consume any narcotic drug or psychotropic substance. Narcotic drugs or addictive drugs are likely to be abused by youngsters. These substances are also capable of altering the mood, behavior and usually induces insomnia. They are also used as primary drugs in the management of pain. The drugs storage room for narcotic substance should have high security with adequate lighting, temperature control below 25 C degree C*, proper selves with lock and keys. The drug storage room is having container to return of unwanted medicine with water supply and soap dispenser and paper tower holder. The narcotic cupboard should be separated and should have independent locking system. Pharmacist who dispenses narcotic medicines should maintain records of input or output and should use red ink for addition or deletion on the narcotic records. Each documented receipt of delivery should be signed by licensed nurse for receiving the drugs (McLellan 2017).

156

A. N. Nagappa and J. Kanoujia

9.2.10 Conclusion Hospital pharmacy can be described as miniature industry within the hospital premises. It is engaged in activities of inventory of medicine and also manufacture of formulations required for the hospital. Bulk formulations like ointments, intravenous venous fluids like normal saline and DNS are manufactured in the hospital itself. Hospital pharmacy saves lot of money for the hospital.

References Abousheishaa AA, Sulaiman AH, Huri HZ, Zaini S, Othman NA, Bin Aladdin Z, Guan NC (2020) Global scope of hospital pharmacy practice: a scoping review. Healthcare 8(2):143 Aldhwaihi K, Schifano F, Pezzolesi C, Umaru N (2016) A systematic review of the nature of dispensing errors in hospital pharmacies. Integr Pharm Res 5:1–10. https://doi.org/10.2147/ IPRP.S95733 Barajaz M, Turner T (2016) Starting a new residency program: a step-by-step guide for institutions, hospitals, and program directors. Med Educ Online 21:32271. https://doi.org/10.3402/meo.v21. 32271 Bazhan SV, Blank BL, Gerov SV (1988) Khranenie iadovitykh i narkoticheskikh lekarstvennykh sredstv v apteke gospitalia [storage of poisonous and narcotic drugs at the hospital pharmacy]. Voenno-meditsinskii zhurnal 8:57 Berger EJ, Jazayeri D, Sauveur M, Manasse JJ, Plancher I, Fiefe M et al (2007) Implementation and evaluation of a web based system for pharmacy stock management in rural Haiti. AMIA Annu Symp Proc 2007:46–50 Callahan RJ (1996) The role of commercial nuclear pharmacy in the future practice of nuclear medicine. Semin Nucl Med 26(2):85–90 Chaghari M, Saffari M, Ebadi A, Ameryoun A (2017) Empowering education: a new model for in-service training of nursing staff. J Adv Med Educ Prof 5(1):26–32 Falconer JR, Steadman KJ (2017) Extemporaneously compounded medicines. Aust Prescr 40(1): 5–8. https://doi.org/10.18773/austprescr.2017.001 Gesme DH, Towle EL, Wiseman M (2010) Essentials of staff development and why you should care. J Oncol Pract 6(2):104–106. https://doi.org/10.1200/JOP.091089 Goodrich TJ, Gorry GA (1980) The process of ambulatory care: a comparison of the hospital and the community health center. Am J Public Health 70(3):251–255. https://doi.org/10.2105/ajph. 70.3.251 Gould O, Buckley P, Doucette D (2013) What patients want: preferences regarding hospital pharmacy services. Can J Hosp Pharm 66(3):177–183 Hahn A, Poison Control Centers (2009) In: Wexler P, Gilbert SG, Hakkinen PJ, Mohapatra A (eds) Information resources in toxicology. Academic Press, Amsterdam, pp 701–710 Hawksworth GM, Chrystyn H (1998) Clinical pharmacy in primary care. Br J Clin Pharmacol 46(5):415–420. https://doi.org/10.1046/j.1365-2125.1998.00818.x Holm MR, Rudis MI, Wilson JW (2015) Medication supply chain management through implementation of a hospital pharmacy computerized inventory program in Haiti. Glob Health Action 8: 26546. https://doi.org/10.3402/gha.v8.26546 Lamarre D, Bertrand M-È, Giroux D, Nordlund JJ, Ertle J, Charles AJ (2009) Compounding dermatologic preparations in developing countries. Dermatol Ther 22:560–563 Liu W, Wosinska ME (2017) The landscape of contract manufacturing of sterile injectable drugs: who is making what, where, and for whom. Ther Innov Regul Sci 51:471–479. https://doi.org/ 10.1177/2168479017696269

9

Hospital Pharmacy Services: Ward Pharmacy, Compounding of Prescription,. . .

157

Marriott JF, Wilson KA, Langley CA, Belcher D (2016) Pharmaceutical compounding and dispensing, 2nd edn. Pharmaceutical Press, London McLellan AT (2017) Substance misuse and substance use disorders: why do they matter in healthcare? Trans Am Clin Climatol Assoc 128:112–130 Morecroft CW, Thornton D, Caldwell NA (2015) Inpatients' expectations and experiences of hospital pharmacy services: qualitative study. Health Expect 18(5):1009–1017 Plumridge RJ, Maher MPAM (1993) Justification of a pharmacy intravenous admixture service in an Australian hospital. Am J Hosp Pharm 50(3):463–466. https://doi.org/10.1093/ajhp/50.3.463 Saha GB (1984) Nuclear pharmacy. In: Fundamentals of nuclear pharmacy. Springer, New York Watson CJ, Whitledge JD, Siani AM, Burns MM (2021) Pharmaceutical compounding: a history, regulatory overview, and systematic review of compounding errors. J Med Toxicol 17(2): 197–217. https://doi.org/10.1007/s13181-020-00814-3

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940, Pharmacy Act 1948, Pharm D Regulations, Bridge Course for Pharmacist, Pharm Drugs and Magic Remedies Act, Pharmacy Practice Regulations 2015, and Jan Aushadhi Scheme

10

A. N. Nagappa and Jovita Kanoujia

Abstract

Ethics and regulations are very important parts establish and nurture professional environment in a community. The ethics provide guidance for one to understand and differentiate what is right and wrong professional practice. They are maintained by professional bodies who are responsible for assuring the compliance by its members. Regulations are required to be followed; otherwise, the regulatory bodies and the public will question the illegal practice and may be punished if found guilty in the court of law. The major charter of ethics is the code of ethics published by pharmacy profession. Regulations are maintained by Drugs Control Department of center and state. Keywords

Code of ethics · Drugs and Cosmetics Act 1940 · Pharmacy Act 1948 · Pharmacy Practice Regulations 2015 · Drugs and Magic Remedies Act 1954

10.1

Ethics and Regulations

Ethics and law are interrelated in a sense that they are having a social purpose of directing and encouraging right conduct among professionals. Profession of pharmacy is directly responsible to protect patient’s health by providing quality medicines and ensuring quality use of medicine. It is well known that every drug A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_10

159

160

A. N. Nagappa and J. Kanoujia

is risky and carries a burden of side effects on patients. Realizing the potential of danger on health, the governments have framed strict laws and established regulatory bodies to monitor a system of ensuring quality of medicines and its rational use. On the contrary, the manufacturer of drugs and its dispensers (community pharmacist) play an important role in handling of drugs. Every aspect of manufacture and dispensing cannot be monitored 24/7; hence, there is a need to give training for positive human behavior and attitude to the professionals. The professional ethics are the guidelines to adopt and practice to gain the trust of the community. The danger of medication errors in the treatment of disease is major issue among healthcare providers. Ethics attempts to achieve its objective of right conduct without the intervention of regulations. Ethics are to be practiced with great commitment so that patient and health consumers develop a sense of trust and confidence. The pharmacist practicing the ethics limitlessly is easy to distinguish in the community. She/he is valued high with respect for the services rendered. The code of ethics proclaims “a pharmacist should not betray or neglect the interest of patient and health consumer (P & HC) even her/his own life is in danger.” The relationship of pharmacist and the patient can be equated with the relationship of a mother and her child. For a young mother, who has become mother for the first time, there is no one to guide or direct her how she should take care of her child. It is her dedication and commitment to provide the best care that make her to learn and provide care for her child. Automatically the inbuilt love and affection for the child drive her to care of her child in all aspects. Ethics unlike law needs to be influenced by professional organizations, in the interest of self-profession and patients. If one does not care for ethics, she/he is easily branded, and the public shall avoid such pharmacist as the person is not trustworthy any more. If the profession comes to the support or remains silent of unethical practices of a member and does not try to prevent such behavior, gradually the public shall lose confidence in the profession itself (Salari et al. 2013). Let us look into the status of pharmacist in developing country and developed country like India and the USA, respectively. Due to the implementation of proper system and regulations, the constant monitoring of the professional activities is in place. Such a system is progressive as one has to maintain dignity and respect in the professional circle and public as well. The services provided by pharmacist should be rewarded by either patients, Insurance companies or by government itself. The pharmacist’s main income does not come from sale of prescription medicine alone, whereas in developing economies all kinds of rules and regulations are enforced but they are not strictly enacted. As a result of this, the pharmacist is not giving any importance to professional practice. They are mainly engaged in selling medicines without care or concern for the public. In a developing country like India, anybody can buy a prescription medicine easily from a medical store. We can say that anyone can buy medicine. It is illegal to sell a prescription medicine to patient without a proper prescription. Due to carelessness in the implementation of law, patients are buying prescription medicines and thus are exposed to the dangers of the irrational use of medicine. For example, topical steroids are abused as beautifying cosmetics. Such unabated abuse has led to the patient succumbing to steroid toxicity and complications of steroids. Is it not the responsibility of the pharmacist and

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

161

professional organization to curtail the use of topical steroid and protect her/his patients? These kinds of attitude and behavior of pharmacist have made the public to think that pharmacist is a drug trader, not a healthcare professional (Resnik et al. 2000). The law attempts to achieve its purpose through the power of constitutions applying judiciary and administrative institutions. For example, if anybody violates law or commit any offence, she/he shall be punished for their offence of violating the law. The law executes control and directs individuals to be obedient and should not allow anyone to cause any harm to the public knowingly or unknowingly. For example, the pharmacist is considered guilty and liable for punishment if he dispenses prescription medicine without a prescription, because as per the Drugs and Cosmetic Act of 1940 it is clearly mentioned that any pharmacist should not dispense prescription medicines without a prescription. This rule has a purpose to control pharmacists and patients in indulging self-medication which is unprofessional and harmful for the health of the public. Ethics are supposed to be unrecorded and practiced voluntarily for the sake of all stakeholders. There should be no force or any compulsion on individuals to be abided by ethical practice and morally up righteously. If ethics are neglected and one behaves in an unethical manner, she/he is likely to become noticed in the community and profession leading to outcasting from the community, whereas the laws and ethics are mandatory to be followed and practiced voluntarily (Pray 2006). Mainly pharmacy profession has a responsibility of making quality medicines and supervising the use of medicines in a rational manner. The manufacturing of medicines relates with industry, and the use of medicine is concerned with the distributions as well as dispensing of medicines. As medicines are having date of expiry, the industry is keen on promoting the consumption of manufactured medicine. On the other hand, dispensing of medicines is dependent on prescription given by a doctor. Doctor has to prescribe the medicine after diagnosing the patient and has to apply professional preference before choosing a medicine for a patient. If wrong medicines were prescribed, then adverse drug reactions which carry a potential to cause serious injuries for patient and health consumer result to serious outcomes. It is the wish of the government that the citizens of the country should remain healthy. It is also true that medicines should be used in case the patient has a disease or condition for achieving good health. Apart from medicine, one should also give importance to healthy lifestyle, balanced diet, and constant monitoring of the conditions. However, in developing countries the health care professionals are focused on treating the patients by prescribing the medicines for a symptomatic relief. The public in developing countries believes that if we get into an illness, then medicines are there to resolve. Confusion and myths rule the public, healthcare provider, as well as manufacturer which are promoting the sale of medicine instead of health and quality of life for patients. The laws and regulations regarding healthcare delivery are continuously updated, and new laws are enacted to provide seamless healthcare delivery. The primary objective of providing health safety and good outcomes of treatments are the commitments of the government (Dessing 2000).

162

10.2

A. N. Nagappa and J. Kanoujia

Pharmacist Oath

Every pharmacist is supposed to take an oath as per the pharmacy regulatory bodies. The Pharmacy Council of India established under the Pharmacy Act of 1948 has framed the oath of pharmacist. The oath for pharmacists commits and guides the pharmacist to understand and practice the pharmacy profession ethically and legally. Pharmacist oath motivates the new pharmacist to understand and practice ethics of the profession. It also affirms pharmacy professionals about the role and responsibility of pharmacist who is being an integral part of the healthcare team. In the pharmacist oath, one pledges to uphold the laws and standard of his/her profession. He makes a promise to take active interest and commits to do his/her best of services toward patient care. She/he shall provide services to patients by means of providing pharmaceutical care and counseling to the patient. Further, she/he shall put continued efforts to do research and manufacturing of new medicines of standard quality to help the suffering patients. She/he should maintain the decorum of the profession and never indulge in revealing the confidential information about a patient to anyone else except when demanded by the court for its proceedings. She/he should continuously take interest in development of her/his knowledge in order to serve P & HC in the best possible manner. She/he should also be associating with local and national professional organizations in order to keep oneself abreast with current happenings and development in profession. Developing a friendly network with fellow pharmacist is in the interest of business, career, and profession. One should consider the pharmacist as a fraternity engaged in service of patients. Mutual understanding and cooperation are essential to provide quality of services. There is no room for unhealthy competition among pharmacists, and by their elegant behavior and practice, the public should develop trust and respect for individual and profession. The pharmacist who dedicates her/his time and resources for the betterment of health shall be rewarded with recognitions, respect, and remuneration. He/she finally accepts to be punished if he/she violates the oath. As a pharmacist, he/she must follow etiquettes of professional diligence and fellowship. He must not criticize any doctor or nurse in public. He should not comment or show any disrespect to fellow healthcare provider. She/he must understand that healthcare delivery is a teamwork and other fellow healthcare providers share a common goal of providing acceptable therapy for the needy patients. He must also get in collaboration with doctor or nurse to exploit the patients by clandestine agreements. The pharmacist oath practice in India is shown in Table 10.1 (Smith and Dinkins 2015). The detail discussion of ethics of pharmacist is discussed below, under the following headlines.

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

163

Table 10.1 The specimen oath of pharmacist I swear by the code of ethics of pharmacy Council of India, in relation to the community and shall act as an integral part of health care team I shall uphold the laws and standards governing my profession I shall strive to perfect and enlarge my knowledge to contribute to the advancement of pharmacy and public health I shall follow the system which I consider best for pharmaceutical care and counseling of patients I shall endeavor to discover and manufacture drugs of quality to alleviate sufferings of humanity I shall hold in confidence the knowledge gained about the patients in connection with my professional practice and never divulge unless compelled to do so by the law I shall associate with organizations having their objectives for betterment of the profession of pharmacy and make contribution to carry out the work of those organizations While I continue to keep this oath unviolated, may it be granted to me to enjoy life and the practice of pharmacy respected by all, at all times! Should I trespass and violate this oath, may the reverse be my lot!

10.3

Pharmacist in Relation to His/Her Job

The pharmacy is a licensed premise under the Drugs and Cosmetics Act 1940 wherein a registered pharmacist provides services such as dispensing of medicine, patient education, and consulting. The pharmacist should be a registered pharmacist in a state pharmacy council. The conduct of pharmacy should be such that there is no risk/error or contamination of the medicines while dispensing and handing over prescribed medicine to the patients. The area should be adequate enough to conduct the activities of pharmacy services. Pharmacy services include compounding and preparing the prescription basket after receiving the cash for dispensing. There should be patient counseling area, reference section, and other amenities for providing professional services. The impression of the premises should be such that it reflects the professional character. It should have proper signs, notices, and descriptions to guide the public for the conduct of the transactions. The pharmacist should always present herself/himself as clean and neat. They should always wear white apron. There should be a place for display of documents in a conspicuous place wherein the public can get to know the pharmacist names, qualifications, and registration certificates. It should also have a notice board to inform about various schemes and programs which are served in the premises, for example, government scheme of directly observed therapy (DOT) for tuberculosis (TB), human immunodeficiency virus (HIV), and other government health programs. It is illegal to perform pharmacy services in the absence of pharmacist. Hence, pharmacist should be available for service and provide pharmaceutical services as mentioned in the notice board. The prescription medicines are to be stocked securely under the custody of a registered pharmacist in a licensed premise. The regulations for pharmacy profession can be disseminated into industrial practice and pharmacy practice. As this book is about pharmacy practice, laws

164

A. N. Nagappa and J. Kanoujia

relating industrial practice shall not be discussed. For better understanding of industrial practice, one should look for bare acts and professional resources. For example, we shall be discussing in great detail the aspects of drug distribution and sale of medicines of the Drugs and Cosmetics Act of 1940 leaving the discussion of manufacturing of drugs (Simpson 2017; Miyares 2013; Beresford et al. 2017).

10.4

Handling of Prescriptions

Prescription is a physician’s order for the preparation and administration of a drug or device for a patient. A prescription has several parts, which include the superscription or heading with the symbol “R” or “Rx,” which stands for the word recipe (meaning, in Latin, to take); the inscription, which contains the names and quantities of the ingredients; the subscription or directions for compounding the drug; and the signature which is often preceded by the sign “s” standing for signa (Latin for mark), giving the directions to be marked on the container. Pharmacist is supposed to interact with patient and health consumer while dispensing prescriptions. Etiquette of handling prescriptions involves inviting the clients with a body language of encouraging them and making the clients comfortable. The pharmacist should not show any expression of alarm or astonishment after seeing the prescriptions. This may lead P & HC to think that the doctor who has written a prescription might have made a mistake. They may even doubt the capacity of the doctor. Pharmacist should not unnecessarily behave in a manner which erodes the patient trust and may cause anxiety in the mind of patients. They should never disclose any information to the P & HC which might have been intentionally withheld in the interest of patient. The role of the pharmacist is to work in liaison with doctor and nurse. She/he should never add or overlook or substitute any medicines or alter the composition of a prescription, without the consent or knowledge of the doctor. She/he should not change the prescriptions and discuss with the doctor confidently and try to convince the doctor regarding the suggestions. In case the pharmacist wants to change the prescription, he can discuss with and convince the doctor. After getting the consent, she/he may change the prescription. This is very important to know that the doctor after concluding the diagnosis of the patient conditions should prescribe the medicines. If there is a chance of incompatibility or a case of overdoses, the prescription should be changed by the prescriber following the feedback given by the pharmacist to the doctor. While refilling the prescriptions, the pharmacist should be guided by the instructions of doctor. Pharmacist should understand that the doctors are the frontrunners and pharmacist and nurses are engaged to facilitate the healthcare delivery to the patients (Dyasanoor and Urooge 2016; Velo and Minuz 2009).

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

10.5

165

Handling of Drugs

Pharmacist should be careful about dispensing and the possibility of misuse of prescription medicines. There are many drugs which are abused by the P & HC. Many drugs are abused for recreation. These might lead to drug addiction and presenting fake prescriptions in order to procure drugs for abusive purpose. In case there is a doubt of drug abuse, he/she can refuse the dispensing. All possible care should be taken while compounding a prescription. Extra care should be taken while reading the quantity prescribed. He/she must not commit mistake while weighing and measuring the ingredients. He/she must take correct proportions and should avoid visual guess. He/she should never fill the prescriptions of spurious and substandard drugs (Botermann et al. 2016).

10.6

Training New Pharmacist

The chief pharmacist exhibits role model qualities in front of subordinates and intern. She/he should never indulge in unethical practices and should not create doubt of integrity in front of trainee pharmacists. Trainee pharmacists are future practitioners; if they observe any wrong practices, they are likely to catch up and adopt the practice when they become practitioners. It is the obligation of every senior pharmacist to train apprentice pharmacist. The internship should be aimed at exposing the interns with skills of pharmacy practice and dispensing. It is professional obligation to train trainee pharmacist and see that the trainees acquire sufficient competence to fulfill the expectations of profession (Knoer et al. 2016).

10.7

Pharmacist in Relation to Her/His Trade

Pharmacist should never charge more money from innocent patients. She/he should also take care regarding the quantity and quality of medicine dispensed. Pharmacist should update her/his knowledge and skills for providing the services and medicines at affordable price. She/he should also charge the patients/insurance/government a professional fee benefiting the labor and skill. Pharmacist should be in a constant learning mode and acquire the knowledge about new drugs and advancement of therapy using the new drugs. Doctors and nurses prefer to get information from the community pharmacist rather than a marketing representative. When patients are paying for the medicine in an out-of-the-pocket model, then the pharmacist should try to balance between pharmacy charges and the patient interest. Further, she/he should not involve in cut-throat competition with other pharmacists in the community. It is unethical to give trade discounts, prizes, and gifts in exchange of business. She/he should also refrain himself from any tempting offers given by manufacturers in order to sell the medicines for profit. While purchasing the drugs for dispensing, she/he should always buy the medicines from authorized genuine distributor and avoid and discourage the buying of medicine from suspicious distributors. This is

166

A. N. Nagappa and J. Kanoujia

important to protect the costumer’s health of the pharmacy. The possession, distribution, and sale of spurious or substandard drugs are unethical and illegal. The hawking of medicines should not be attempted such as selling the medicines door to door. This practice can lead to handing over therapeutic drug to patient which may lead to misuse (Goel et al. 1996). Pharmacist should never be overenthusiastic in selling medicines or medical devices in an undignified manner. She/he should never advertise and display any wording which is offending to any group or individuals further in order to impress and increase sales. She/he should not make any exaggerated statements and claims which are misleading. The pharmacy should never offer to refund money or conduct competitions and offer prizes. This type of sale promotion is common in jewelry shops and consumer durables. Such practices shall erode the professional image and reputation of pharmacy in due course. While making reference to a medical practitioner or hospital or nursing home, she/he should do it in the interest of patient. She/he should not have any secret liaison or kickback arrangement for reference of a patient to a particular doctor, hospital, or nursing home. It is very much offending to promote and recommend medicines for patients who approach pharmacy for drugs to improve sexual weakness, premature aging, or loos of virility (Goode et al. 2019). The scope of pharmacist is changing from traditional services like compounding and dispensing to healthcare provider. The pharmacist is indulging in pharmaceutical care, and service like vaccination, diabetic care, and obesity management is permitted by law. In view of this provision, they should not compete with doctor or nurses. They should work in harmony with fellow pharmacist and other healthcare providers to avoid ill feelings. Pharmacist should keep his/her knowledge abreast with developments regularly as a member of local, national, and international professional organizations. He should participate in continuing education program conducted by council and professional societies. In many countries, the pharmacist is required to qualify in licensing examination, and based on the performance, pharmacist license is renewed. This system is to ensure minimum standards of practice. As a law-abiding citizen and member of the community, she/he should restrain from doing things which destroy and cause harm to the society as well as profession. She/he should not be afraid to face and prevent a miscreant from doing harm to the society and profession. She/he should be a model civilian to be followed by others in matters of health and sanitation. She/he should not smoke or chew tobacco products in public purview and in front of patients. This would give a wrong message to the public who shall think as the pharmacist himself is smoking and chewing tobacco, it may not be harmful to health (Kehrer et al. 2013).

10.8

Pharmaceutical Jurisprudence

The government’s major responsibility is to establish functional legal system to ensure safe, reliable healthcare delivery system. The healthcare delivery is being a part of teamwork which involves three different professions. It is very necessary to

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

167

establish a stable and cooperative environment which is conducive to practice and deliver services. The pharmacy profession is engaged in making formulations of medicines and developing a system of efficacy with medicine safety as drugs are like double-edged sword. The prescription drugs should be kept away from public; at the same time, medicines should be made available for the patients and healthcare professionals for use. In order to resolve these issues, the government has enacted several laws and regulations. The important laws of drug are discussed in the context of India (Stevens 1963). In pre-independent era, there were no laws and regulations to control import, manufacturing, distribution, and sale of drugs in India. The quality of medicines available in the country was not trustworthy; obviously, substandard drugs were in circulation. The British rule has initiated an inquiry under the leadership of Col R. N. Chopra. He reported the status of healthcare and quality of medicine. Col Chopra made a thorough investigations and submitted the report which was published in an Indian medical gazette on January 1932 (PP29). Report in Indian medical gazette led to the passing of the Drugs and Cosmetics Act 1940 and rules under the Drugs and Cosmetics Act 1945, which was extended to whole of British India. The objective of the inquiry was to do a survey and report on to what extent the drugs and cosmetics in the market are purely used as medicines. The report made observation and stated that many medicines contain no medicine or it contains chalk powder or turmeric powder instead of medicines. At that time, there were no pharmaceutical industries in India, and all medicines were imported, distributed, and sold in British India. The committee has to recommend about indigenous medicines that were used in the country such as Ayurveda, Unani, and Siddha medicines. The report was also expected to suggest necessary laws to develop the profession of pharmacy to train the qualified pharmacist. This report has led to the enactment of Drugs and Cosmetics Rules of 1940 and Pharmacy Act of 1948. There was a lot of false information about drugs being published in print media by unscrupulous merchants to lure innocent public to use medicine. In order to curb such advertisements, Drugs and Magic Remedies Act 1954 was enacted.

10.9

Drugs and Cosmetics Act 1940 and Drugs and Cosmetics Rules 1945

The aim of Drugs and Cosmetics Act 1940 and Drugs and Cosmetics Rules 1945 was to control the import, manufacturing, distribution, and sale of drugs and cosmetics through licensing. The license was given to the qualified pharmacist in order to prevent entry of substandard drugs in the market. To control and supervise the associated activities, proper administrative body was established. Similarly, rules were enacted to regulate the manufacturing, distribution, and sale of Ayurveda, Unani, and Siddha medicines (Roderick et al. 2014). Organizational chart of drug administration is given in Table 10.2. The allopathic medicines carry a risk of adverse drug effect which can harm patient’s health. They need to be prescribed after evaluation of risk benefit analyses

168

A. N. Nagappa and J. Kanoujia

Table 10.2 Organizational chart of drug administration Drug administration Advisory Drug technical advisory board Drug consultative committee

Analytical Central drug labs Drug labs in states Government analyst

Executive Licensing authority State drug control department Drug inspectors

Fig. 10.1 Movement of allopathic drugs from wholesaler to patients

for a patient by a registered medical practitioner. Allopathic medicines are of chemical origin and are capable of having intense effect on the health of a person. The patients/public are supposed to use these medicines by recommendation of a doctor through a prescription. These medicines are in the custody of wholesalers, C & F agents, and retail pharmacist. The retail pharmacist who is registered pharmacist is licensed to dispense medicines to patients on recommendation by doctor/nurse through prescription. This is essential to prevent drug-induced harm to the patients and public. The pharmacist by her/his knowledge, skill, and practice is supposed to ensure patient education and counseling while dispensing the medicines. Fig. 10.1 graphically represents the movement of allopathic drugs from wholesaler to patients.

10.10 Pharmacy Act 1948 Pharmacy Act Bill 1947 led to the Pharmacy Act 1948. Prior to 1947, pharmacy was practiced by anyone who has no background or educational training about drugs and medicines. If someone is proficient in basic English, she/he ventured into selling of medicine to the public. There was poor quality of pharmacy services, and due to it, great harm was happening to the health of the patients and health consumers, in the absence of trained and qualified pharmacist. Educational facilities do not exist in the country, and pharmacists have to go abroad to get qualifications of pharmacy. The objective of Pharmacy Act 1948 is to establish educational facilities and

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

169

institutions to develop pharmacy profession in the country. Central and state pharmacy councils are established to make provision for registration of pharmacist who have completed pharmacy qualifications like diploma in pharmacy, bachelors in pharmacy, and PharmD and undergone stipulated training. Initially, pharmacist shall register in a state pharmacy council. Each state pharmacy council shall be sending the details of registered pharmacists to the central council to include its names to registered pharmacists. To frame the standards for educations and training for the pharmacist, every state in India should establish state pharmacy council. State pharmacy council is supposed to maintain first registration of registered pharmacist. Registered pharmacist is eligible to practice pharmacy in retail pharmacy, pharmacy, central pharmacy, and satellite pharmacy. Periodically, state pharmacy council shall be sending the list of registered pharmacists to the central council where they maintain list of registered pharmacists in the country. The registered pharmacist should always carry certificate of registration and be shown in the licensed premises during pharmacy practice. The central pharmacy council is accredited to recognize the qualifications of foreign pharmacist and give them an equivalence certificate after evaluation and allow them to practice pharmacy profession (https://legislative.gov. in/sites/default/files/A1948-8.pdf).

10.11 Pharm D Regulations In 2008, Pharmacy Council of India introduced Pharm D Regulations 2008. Pharm D Regulations aim at education and training pharmacist to work as competent clinical hospital and community pharmacist. Pharm D Regulations were approved by the Ministry of Health and Family Welfare, Government of India, which notified the gazette of India Part IIII, Section 4, no. 19 dated 10 May 2008. The PharmD qualification is a 6-year program after 10 + 2 in science with major subjects like physics, chemistry, mathematics, or biology. Diploma in pharmacy candidate is eligible to do regular PharmD, while individual with bachelor in pharmacy is eligible to do a 3-year PharmD postbaccalaureate. PharmD has to complete 1 year of internship which is the final year of PharmD. The last year in PharmD or PharmD PB involved 1 year internship in 300 bedded hospitals. The hospital should have, apart from general medicine, Four specialty departments like nephrology, gynecology, cardiology and pediatrics. The rotation in general medicine along with other three departments is the components of internship. The PharmD qualification is considered equivalent to postgraduate and is eligible for taking admission in PhD. The syllabus of 6 years makes the students to take up upon clinical services as a clinical pharmacist in hospitals. They are supposed to cover 200 hours of working in each year starting from second, third, fourth, and fifth year. Every student shall spend half a day in the morning hours for ward rounds on a daily basis as part of clerkship. Theory teaching may be scheduled in the afternoon. The project work allows the students to develop scientific temperament of data collection and reporting skills in the area of community, hospital, and clinical pharmacy.

170

A. N. Nagappa and J. Kanoujia

Internship should focus on specific objectives to provide patient care in cooperation with doctor and nurses along with other inter-professional healthcare team. An intern shall participate with therapeutic team as a clinical pharmacist by bringing knowledge which improves the patient safety and efficacy of treatments. The interns should offer services of clinical pharmacy and try to get accorded by doctors. Initially, in the beginning, doctors are likely to avoid interns as they think the clinical pharmacist intern is interference in their practice (Deshpande et al. 2012; Pharmacy Council of India 2008). Interns should be able to understand and adapt to legal, ethical social, cultural, economic, and professional issues pertaining to the patient care. They should also be sensitive in the matters of pharmaceutical behavioral, administrative, and clinical knowledge which may have influence on therapeutic outcomes. It is expected that an intern shall be able to manage and use resources of the healthcare system in cooperation with patient and healthcare team. Intern should participate in logistics to provide access to the medicines by improving distribution channels. Intern shall be taking active interest in patient education and counseling as well as motivating in promotion of health improvement. She/he should also promote wellness and disease prevention with the participation for the sake of learning and helping in the national health program. The public health is an effective tool to provide healthcare to masses. The pharmacist should take the leadership in national schemes, such as AIDS prevention, pulse polio, and malaria eradication programs. They should develop leadership skills in organizing and delivering health and family welfare services in the community. Overall, they must have proficiency in communication with P & HC.

10.12 Bridge Course for Pharmacist The Pharmacy Act of 1948, as on today, has a provision to register diploma in pharmacy as registered pharmacist. The registered pharmacists are employed as pharmacist in government and private hospitals. The registered pharmacists are also self-employed in their own medical stores. They are also employed as registered pharmacist in medical stores. The knowledge and skill levels of diploma in pharmacy are not adequate enough to provide pharmaceutical care to the patients. Keeping in view of this, the Pharmacy Council of India (PCI) has launched BS in Pharmacy and pharmacy practice operations in order to upgrade the knowledge and skill levels of practicing pharmacist. A new program was introduced by the Government of India by gazette notification Bachelor of Pharmacy (Practice) Regulations 2014 under Sect. 10 and Sect. 18 of the Pharmacy Act 1948. The pharmacist in the country is presently engaged in drug store management and retail marketing of drugs. In order to update the quality of services, the PCI has launched this program. Currently, registered pharmacists work in the government sector and in retail pharmacies. They are mainly engaged in drug store management and dispensing; these two activities are not enough to provide rational drug therapy. Pharmacist’s contribution in the matters of rational

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

171

use of drugs and healthcare management along with prevention of ADR and providing patient safety as well as quality outcomes of bachelor of pharmacy (practice) is essential. This course is being offered to registered pharmacists who are working as in-service pharmacist and retail pharmacist. They are supposed to do this course along with their job; the classes are likely to be conducted on Saturdays and Sundays. They have to study all the basic healthcare sciences and social sciences which are essential to take up the pharmacy practice. Syllabus includes pathophysiology, pharmacotherapeutics, pharmacy practice, applied pharmaceutics, social pharmacy, and pharmaceutical jurisprudence.

10.13 Drugs and Magic Remedies (Objectionable Advertisements) Act 1954 Drugs and Magic Remedies (Objectionable Advertisements) Act 1954 is an act of the parliament of India with controls over advertising of drugs in India. It prohibits advertisements of drugs and magic remedies that claim to have magical properties and cheat the public to get money illegally. The Act defines “magic remedy” as powers to cure, diagnose, prevent, or mitigate a disease in humans or animal. It also includes such devices that are claimed to have power to influence structure or function of an organ in humans or animals. It bans talisman, mantra, amulet, or any other object which is claimed to have miraculous power. The law prohibits advertising of drugs and remedies for inducing miscarriage or preventing conception in women, improving or maintaining the capacity for sexual pleasure, correction of menstrual disorders, and curing, diagnosing, or preventing any disease or condition mentioned in an included schedule. Medicines are to be controlled and should not be advertised like consumer items. Medicines are to be used with discretion as they are capable of doing harm if used by the common man to treat her/his disease, in selfmedication. In the absence of the Drugs and Magic Remedies Act (D & M), many unscrupulous traders and businessmen were cheating the public by stating exaggerated claims of cure of diseases. In India, P & HC are innocent and believe the information advertised in mass media like print, TV, and radio. The advertisement aimed at selling dangerous medicines by cheating need to be curbed. The D & M Remedies Act of 1954 provides legal sanction to punish fake medicine seller with fake claims. This Act although is in enforcement doesn’t have in administrative backup like Drugs and Cosmetics Act of 1940 and Pharmacy Act of 1948 (Ayyanar et al. 2018).

10.14 Pharmacy Practice Regulations 2015 After getting independence in 1947, there was an urgent need to meet the drug scarcity issue and also a concern about drainage of money out of the country for the import of drugs. To address this issue, the Government of India took several

172

A. N. Nagappa and J. Kanoujia

decisions to create an environment for growth of the pharmaceutical industry. The public sector industries like Hindustan antibiotics, Indian drugs, and pharmaceuticals limited and state government-based industries like Karnataka Antibiotics and Pharmaceuticals Ltd. and Rajasthan Antibiotics and Pharmaceuticals Ltd. were started. The India Patents Act 1970 was enacted and had product patent, ignoring the process patent. This encouraged indigenous pharmaceutical industries to produce the patented product by reverse engineering and changing the process of manufacture. India has emerged as a hub of cheap medicines in the world. The government, although enacted proper laws and regulations to ensure patient safety, didn’t enforce the existing laws in its true spirit. Due to this laxity, the community pharmacy did not grow. The pharmacist was only interested in selling medicines. Pharmacist never took keen interest in patient’s safety. Hence, unlike in developed countries, one can buy a prescription medicine just by asking. Irrational use of medicine is very rampant. Unethical mindset has become acceptable. The profession of pharmacy is at its low. The pharmacy services are unheard in the country. In India, after enacting Pharm D Regulations 2008 and Bachelor of Science (Pharmacy Practice) Regulation 2014, it was the responsibility of the government to prepare the platform for PharmD and Bachelor of Science (Pharmacy Practice) career opportunities. Conventionally, pharmacists were engaged in manufacturing, distribution, and sale of medicines. The sale of medicine was limited to handing over pre-manufacture unit packs to the P & HC. During education, pharmacists are oriented to provide patient counseling and other services and never dared to take up the pharmacy practice service to the institutional level. Otherwise, the importance of pharmacist in the pharmacy just remained merely as legal requirement than a professional necessity. Many retail pharmacy outlets across the country started functioning even in the absence of registered pharmacist. Even today, public perceptions about a pharmacist are very low. Similarly, other healthcare providers don’t know much about the role of a pharmacist in healthcare delivery. The Pharmacy Practice Regulations 2015 was enacted by the Government of India in 2015. The Pharmacy Practice Regulations 2015 aimed at enhancing the status and practice opportunities for pharmacy profession in the India. These regulations are the first comprehensive changes introduced to the outdated provisions in the laws governing the pharmacy. New sets of regulations in 2015 lay down a uniform platform of pharmacy ethics, responsibilities of pharmacist toward patient, job profile of a pharmacist, role of a community pharmacist, drug information of pharmacist, etc. The new age pharmacists are expected to interact with patients, doctors, and nurses and engage in educating the patients in a collaborative care model. The thrust of pharmacy practice in developed countries has shifted from product-centric to patient-centric with the implementation of modified drug laws backing patient safety. The pharmacy profession in India has not yet received the status and respectability. It does not provide services. Pharmacists remained more as an invisible community, occasionally seen at the retail pharmacy counters handing over medicines prescribed by the physicians.

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

173

Eliminating the role of a pharmacist from healthcare system had very bad consequences on healthcare delivery. In the absence of effective prescription audit system and with unquestionable authority to prescribe, the doctors tend to neglect patient’s interest and indulge in overprescribing for monetary gains from pharmaceutical companies. This dangerous trend in healthcare practice prevails despite warnings by the Medical Council of India on erring doctors. Pharmacist at a retail counter has a key role to play here to help the patients. The role and responsibility of a pharmacist should be strictly implemented so as to ensure timely intervention for the benefit of patients. The current laws do not empower the pharmacists for such interventions. With the new regulation coming into force now, the relevant provisions both in the Pharmacy Act and D & C Act need to be synchronized to avoid any contradiction. Here, we must see the economic status and earnings of the pharmacist also. The pay structure and earnings in business are of low standard compared to other healthcare providers. The retail pharmacist’s only source of income is margin on sales. There is no respect or value for the services rendered. This has demotivated the retail pharmacist to remain away from learning and providing pharmacy services to patient and health consumers. The Pharmacy Practice Regulation (PPR) 2015 defines pharmacy practice as interpretation, implementation, evaluation, and dispensing of prescriptions and drug order. Pharmacy practice is the active participation of a pharmacist in the selection of drugs and devises in a clinical situation as per the law. She/he is empowered to do drug administration, review drug regimen, and engage in patient-related research of drug and social pharmacy. Provision of the act legally empowers a pharmacist for providing patent counseling and other services required by the patient. She/he is also supposed to provide patient counseling and comfort the patient. She/he is legally authorized for compounding medicines and also labeling of medicine in a hospital setup for the use of medicine for the hospital patients. Her/his responsibility of proper storage of drugs and devises along with maintenance of records of medicines is an important responsibility in a hospital. There is a need for customized dose of medicines which are ordered by the doctors for a particular patient. It happens so in medical practice that the doctor may demand the particular dose which may not be available under regular manufacture medicines. In such circumstances, the pharmacist should be able to compound and provide medicine as required by the doctor. The scope of compounding is regaining its importance as the doctors are becoming patient-oriented. Compounding is extended to supply of extemporaneous preparations by the doctors. The main advantages of extemporaneous medicines are to be freshly prepared and consumed. There is no need for any preservatives as they are consumed immediately. Compounding involves preparation, mixing, assembling, and packaging and labeling drug or devices. PPR 2015 defines dispensing as interpretation, evaluation, supplying, and implementation of a prescription including preparation and delivery of medicines or devices to patient and attendant of a patient in a container with a suitable label for administrations or use in a patient. The pharmaceutical care embodies drug therapy

174

A. N. Nagappa and J. Kanoujia

and patient care services which are intended to achieve positive outcomes for a therapeutic intervention. It also focuses on patient safety along with minimization of patient’s symptoms and also slowing the progression of the diseases. The aim of the pharmaceutical care is to check whether the patient is receiving the medicines as per the requirement. Is there a case of overutilization or underutilization of the medicines? Are there any instances of therapeutic duplication? For example, in India, there are more than one lakh branded medicines which are registered, and these medicines invariably contain roughly 800–900 active pharmaceutical ingredients. One serious issue the pharmacists and patient community facing today in India is the direct selling of medicine by the prescriber himself because of a controversial provision in drug laws. The condition for the provision was made due to shortage of registered pharmacists to dispense in the country immediately after independence. It provided a chance to doctors to sell medicines directly to patients, eliminating the role of a pharmacist from healthcare management. In the absence of effective prescription audit system and with unquestionable authority to prescribe, the doctors tend to neglect patient’s interest and indulge in overprescribing for monetary gains from pharmaceutical companies. This dangerous trend in healthcare practice prevails despite warnings by the Medical Council of India on erring doctors. Pharmacist at a retail counter has a key role to play here to help the patients. For this, there is a need to redefine the role and responsibility of a pharmacist so as to ensure timely intervention for the benefit of patients. There is a need for evaluation of prescription for therapeutic duplication, due to the availability of online updated databases like Lexicomp and Micromedex. It is possible to identify drug-disease interaction and drug-drug interactions and prevent a casualty before it happens. Here, the pharmacist is supposed to discuss this matter with the prescriber and suggest her/him to correct the prescription in the interest of the patient. Pharmacist is also supposed to identify incorrect drug doses or duration of drug therapy. Another area of importance is drug allergy episodes wherein a pharmacist maintains the allergic history of individual patient. In case she/he comes across such an incident, she/he alerts the prescriber along with the patient about happening of allergy interaction. Pharmacist can even suggest the patient to wear a hand band alert. Pharmacist with her/his background and experience should be able to identity episode of artificial shortage of drug, clinical abuse, and clinical misuse. He must ensure steady supply of quality medicine for her/his patients in the community. The clinical abuse of prescription medicines is another major challenge pharmacist is facing nowadays in pharmacy practice. Especially the handling and selling of codeine containing cough syrups, tramadol containing narcotic analgesic. There may be some unscrupulous doctors who may be involved in clinical misuse of medicine, for example, abuse of antibiotics. There may be a secret in understanding between doctor and pharmaceutical industry to prescribe antibiotics even for fever, cough, and cold. The pharmacist should raise an alarm and resist such prescription (https://www.pci.nic.in/pdf/Pharmacy%20Practice%20Regulations.pdf).

10

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . .

175

10.15 Jan Aushadhi Scheme Prices of medicine are fixed by manufacturer depending on the situation. When a manufacturer introduces a new medicine with much improved therapeutic benefits, the manufacturers first ensure the infringement of the medicine by registering them as patent. The manufacturer keeps the price at a higher end as he is in hurry to achieve economic stability and recover the money spent on research. Manufacturer may not be interested in patients who cannot afford medicine due to poverty. After the expiry of the patent, the generics are launched which are supposed to bring down the prizes. However, drugs again are sold as combination formulation, which again are made expensive. The governments are aware of this issue and tried their best to control the medicine prices. They have enacted the Drugs Prices Control Order (DPCO) under Sect. 3 of the Essential Commodities Act 1955. This has enabled the government to declare a selling price for essential and lifesaving medicines (as per a prescribed formula). In India, the patients usually buy medicines in out-of-the-pocket model as the health insurance and reimbursement for medicines are not popular. It is very disheartening to know that despite of the Drug Prices Control Order, medicines are still expensive and patients feel difficulty in meeting the medicine cost. In India, a lot of brands of medicine are available in the market with similar formulations. The prescribers are writing expensive brands to patients, despite of less expensive medicine availability, and patients are endorsed as well as made to use expensive medicine. The pharmaceutical marketing is able to push the expensive brands by influencing the doctors. There are several reforms and amendments in pipeline to streamline the healthcare delivery to be more transparent and accountable, such as the amendments in Drugs and Cosmetics Act regarding banning of medicines sold by prescriber. The law regarding prescribing medicines in generic names and legalizing the substitution of expensive brand with affordable medicine by pharmacist in consultation of prescriber should be followed. These reforms are aimed at making the treatment and cost of medicines under control. Patients with chronic disease like diabetes mellitus, hypertension, asthma, and cardiac disease need to take medicines for several years to live long. Due to ignorance of patients and nonavailability of pharmacy services, the patients are being exploited. The mutual partnership of pharmaceutical industries and prescribers for selling drugs by hoodwinking the drug price control regulations is going to end sooner. The National Pharmaceutical Pricing Authority (NPPA) is an independent body of experts under the Minister of Chemicals and Fertilizers launched in the year 1997. The NPPA’s main objective is to implement and enforce the provisions of the Drug Prices Control Order for regulating the medicine prices. Drug Prices Control Order was first enacted in 1995 and recently in 2017. As per the provision of DPCO 2013, only the prices of drugs mentioned in the National List of Essential Medicines were monitored and controlled by the NPPA. NPPA notified the 348 medicines with specified dosage and strength to monitor the price. Pharmaceutical market in India is categorised as branded and generic market, where doctor prescribe the branded medicines to be consumed by the patient, rather than the generic medicines. Despite of low-cost

176

A. N. Nagappa and J. Kanoujia

generics, doctors prefer to prescribe leading brands which are expensive. Expensive drug brands are also preferred by the patients as they have faith in their doctors. Hence, the patients have no choice to switch over to low-cost equivalents of the expensive brands. The government’s concern is for the patients who cannot afford expensive brand medicines. To take medicine price issue head on, the government came out with the Jan Aushadhi scheme. Medicines are made available at affordable price, medicines belonging to chronic diseases are identified, and the Bureau of Pharma Public Sector Undertakings of India (BPPI) has been established under the Department of Pharmaceuticals, Government of India, with the support of all the public sector units for co-coordinating procurement, supply, and marketing of generic drugs through Pradhan Mantri Bhartiya Jan Aushadhi Pariyojana Kendra (PMJK). PMJAK is a central government initiative launched by the Department of Pharmaceuticals, Government of India, to provide quality medicines at affordable prices to the patients through dedicated medical shops known as Pradhan Mantri Bhartiya Jan Aushadhi Kendra. Pradhan Mantri Bhartiya Jan Aushadhi Pariyojana Kendra (PMBJAK) has been set up to provide generic drugs, which are available at lesser prices but are equivalent in quality and efficacy as expensive branded drugs (Mukherjee 2017; Thawani et al. 2017). Medicines in India are available at different prizes with the range of 30 to 200 percent difference as shown in Table 10.3.

10.16 Conclusion Ethics are well-defined principles that guide professionals to establish a profession in the society. It talks about right things to do and wrong things to avoid. New professionals and students are asked to take oath upon entering the profession. There are adequate laws and regulations which are enough to control the offenders of law. Ethics guide the pharmacist to take a stock of correct behaviors and motivate the pharmacist to adherence to establish the dignity of the profession. Moreover, regulations are meant to be strictly adhered. Any violations are to be punished in the court of law.

10

Vial and wfi Vial and wfi Vial and wfi 10 10 10

Cefixime 200 mg film-coated tablet IP

Cefoperazone 500 mg + sulbactam 500 mg IP Cefoperazone 1 g inj. IP

Cefotaxime 250 mg + sulbactam 125 mg inj

Ceftriaxone 1 g + tazobactam 125 mg inj

Ceftriaxone 250 mg inj. IP

Cephalexin 500 mg capsule IP

Ciprofloxacin 500 mg film-coated tablet IP

Levofloxacin 500 mg film-coated tablets IP

04

05

06

08

09

10

11

12

13

07

3

Azithromycin 500 mg film-coated tablet IP

03

Vial and wfi Vial

10

Amoxicillin 500 mg + clavulanic acid 125 mg film-coated tablets Amoxicillin 500 mg capsule IP

02

Unit 2 mL vial 6

Medicine Amikacin 250 mg inj. IP

S. no. 01

Table 10.3 Discrepancy in medicine prices in Indian market

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Therapeutic group Anti-infective

35.74

22

51.34

11.8

44.46

18.59

31.2

31.61

44.63

25.98

26.25

52.24

Jan Aushadhi/lowest price (INR) 11.35

Open market price/brand name (INR) 37.00 (bloc in) 120.00 (abclox-cv) 72.15 (Acmox) 75.00 (Aicin) 150.00 (Acfix) 200.00 (Acmetum) 244.00 (Cefaperacin) 24.00 (Augtax) 118.80 (Baricef-t) 30.00 (Aacef) 157.22 (Ceff) 75.00 (Abact) 89.00 (ab-cin)

Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . . (continued)

53.26

53

105.88

18.2

74.34

5.41

212.8

168.39

105.37

49.02

45.9

67.76

Difference in price 25.65

10 177

Ofloxacin 200 mg film-coated tablets IP

Vancomycin 500 mg iv infusion IP

Calamine lotion 100 mL

Povidone iodine 7.5% solution IP

Glibenclamide 5 mg tablets IP

Glimepiride 2 mg tablets IP

Gliclazide 80 mg tablets IP

Insulin inj. IP 40 IU/mL

Metformin hydrochloride 500 mg tabs

Pioglitazone 30 mg tablets IP

Telmisartan 40 mg IP + amlodipine 5 mg tabs Diltiazem table 30 mg

15

16

17

18

19

20

21

22

23

24

25

26

Medicine Meropenem 1 g inj. IP

S. no. 14

Table 10.3 (continued)

10

15

10

10 mL vial 10

10

10

Vial and wfi 100 mL bottle 500 mL bottle 10

Unit Vial and wfi 10

Antihypertensive

Antihypertensive

Antidiabetic

Antidiabetic

Antidiabetic

Antidiabetic

Antidiabetic

Antidiabetic

Anti-infective

Anti-infective

Anti-infective

Anti-infective

Therapeutic group Anti-infective

7.8

15.16

11.55

4.4

118.61

16.86

2.89

5.00

105.44

19.52

90.82

14.8

Jan Aushadhi/lowest price (INR) 255.41

Open market price/brand name (INR) 3255.00 (Adi-penem) 72.00 (biofast) 389.00 (Vancomate) 175.44 (Allsuth) 155.00 (Alphadine) 18.50 (Diolin) 45.00 (diagraph) 66.50 (Euclide) 145.00 (Actrapid) 40.00 (Alnamet-SR) 43.10 (G-tase) 83.32 (Amlopres-tl) 22.70 (dilticard) 14.9

68.16

31.55

35.6

26.39

49.64

42.11

13.5

49.56

155.92

298.18

57.2

Difference in price 2999.59

178 A. N. Nagappa and J. Kanoujia

Propranolol tablets IP 40 mg

Ramipril 5 mg + hydrochlorothiazide 12.5 mg tablet IP Metoprolol 25 mg tablets IP

Spironolactone 25 mg tablets IP

Ramipril 5 mg tablets IP

Telmisartan 40 mg tablets IP

27

28

29

30

31

32

10

10

15

10

10

10

Antihypertensive

Antihypertensive

Antihypertensive

Antihypertensive

Antihypertensive

Antihypertensive

7.61

6.93

24.06

3.98

9.1

4.95

36.00 (Albeta-sr) 118.00 (Cardiopril-h) 34.00 (Actocard) 30.00 (Aldactone) 82.43 (Cardace) 69.33 (Arbitel) 61.72

75.5

5.94

30.02

108.9

31.05

10 Ethics and Regulations: Pharmacist Oath, Drugs and Cosmetics Act 1940,. . . 179

180

A. N. Nagappa and J. Kanoujia

References Ayyanar R, Boyanagari M, Shankar M (2018) Enforcement of the drugs and magic remedies (objectionable advertisements) act, 1954, in the state of Andhra Pradesh: situational analysis and lessons learnt. J Pharm Health Serv Res 9(1):47–52 Beresford L, Dagenais R, Hong J, Louie S (2017) Should institutional pharmacy managers maintain an active clinical practice? The “pro” side. Can J Hosp Pharm 70(1):47–48 Botermann L, Krueger K, Eickhoff C, Kloft C, Schulz M (2016) Patients' handling of a standardized medication plan: a pilot study and method development. Patient Prefer Adherence 10:621–630. https://doi.org/10.2147/PPA.S96431 Deshpande PR, Farooq KK, John DM, Rao EJ (2012) Pharm D: a new concept in India. J Pharm Bioallied Sci 4(1):84–86. https://doi.org/10.4103/0975-7406.92746 Dessing R (2000) Ethics applied to pharmacy practice. Pharm World Sci 22:10–16 Dyasanoor S, Urooge A (2016) Insight into quality of prescription writing - an institutional study. J Clin Diagn Res 10(3):ZC61–ZC64. https://doi.org/10.7860/JCDR/2016/18011.7472 Goel P, Ross-Degnan D, Berman P, Soumerai S (1996) Retail pharmacies in developing countries: a behavior and intervention framework. Soc Sci Med 42(8):1155–1161 Goode JV, Owen J, Page A, Gatewood S (2019) Community-based pharmacy practice innovation and the role of the community-based pharmacist practitioner in the United States. Pharmacy 7(3):106. https://doi.org/10.3390/pharmacy7030106 Kehrer JP, Eberhart G, Wing M, Horon K (2013) Pharmacy's role in a modern health continuum. Can Pharm J 146(6):321–324. https://doi.org/10.1177/1715163513506370 Knoer SJ, Eck AR, Lucas AJ (2016) A review of American pharmacy: education, training, technology, and practice. J Pharmaceut Health Care Sci 2:32. https://doi.org/10.1186/s40780016-0066-3 Miyares MA (2013) The attending pharmacist: roles and responsibilities. Hosp Pharm 48(9): 713–714. https://doi.org/10.1310/hpj4809-713 Mukherjee K (2017) A cost analysis of the Jan Aushadhi scheme in India. Int J Health Policy Manag 6(5):253–256. https://doi.org/10.15171/ijhpm.2017.02 Pharmacy Council of India (2008) Pharm D: Regulations 2008. The Gazette of India, No. 19, Part III, Section 4 Ministry of Health and Family Welfare (Pharmacy Council of India) 2008. May 10, pp. 1–97. http://pci.nic.in/PD-Files/PharmD-Revised-A.pdf. [Last cited on 2011 May 27] Pray WS (2006) Ethical, scientific, and educational concerns with unproven medications. Am J Pharm Educ 70:141 Resnik DB, Ranelli PL, Resnik SP (2000) The conflict between ethics and business in community pharmacy: what about patient counseling? J Bus Ethics 28:179–186 Roderick P et al (2014) India should introduce a new drugs act. Lancet 383(9913):203–206 Salari P, Namazi H, Abdollahi M, Khansari F, Nikfar S, Larijani B, Araminia B (2013) Code of ethics for the national pharmaceutical system: codifying and compilation. J Res Med Sci 18(5): 442–448 Simpson SH (2017) The roles we have as hospital pharmacists. Can J Hosp Pharm 70(1):3–4. https://doi.org/10.4212/cjhp.v70i1.1620 Smith MG, Dinkins MM (2015) Early introduction to professional and ethical dilemmas in a pharmaceutical care laboratory course. Am J Pharm Educ 79(10):156. https://doi.org/10.5688/ ajpe7910156 Stevens C (1963) Pharmaceutical Jurisprudence. Nature 198:819. https://doi.org/10.1038/198819a0 Thawani V, Mani A, Upmanyu N (2017) Why the Jan Aushadhi scheme has lost its steam in India? J Pharmacol Pharmacother 8(3):134–136. https://doi.org/10.4103/jpp.JPP_38_17 Velo GP, Minuz P (2009) Medication errors: prescribing faults and prescription errors. Br J Clin Pharmacol 67(6):624–628. https://doi.org/10.1111/j.1365-2125.2009.03425.x

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance, Pediatrics, Geriatrics, Women During Pregnancy, Cancer, Pain Management, and Nutrition

11

A. N. Nagappa and Jovita Kanoujia

Abstract

Pharmacy comprises of a variety of molecules with potential of action on the living body. The optimization of the use of medicines needs careful consideration of drug-related factors matched with patient-related factors. The customization of therapy for a patient in dynamic fashion is the objective of specialty pharmacy services. Pharmacovigilance is keeping the track of adverse drug reaction (ADR) of drugs and alerting the regulatory bodies to review the approval of the use of existing drugs. The principles of drug usage in special populations are discussed in this chapter. Keywords

Specialty pharmacy services · Pharmacovigilance · ADR reporting · Special populations

11.1

Specialty Pharmacy Services (SPS)

Specialty pharmacy services is a growing sector dedicated for research, managing speciality medicines and to treatment cost. Specialty pharmaceutical is used for the treatment of diseases with unique nature, such as rheumatoid arthritis and cancer, and innovative management approaches are needed to utilize the resource and bring down the costs by identifying the loopholes and lacunae in existing services. It attempts to integrate the existing system taking account of current procedures and logistics and optimizes the utilization. It synchronizes care management and managed care contracting between hospitals and independent physicians. It may also A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_11

181

182

A. N. Nagappa and J. Kanoujia

establish relationship with community pharmacies, chain pharmacies, and health maintenance organizations (HMO). HMO offers a healthcare service via a network of healthcare professionals with coverage for a wider range of preventive healthcare services. HMO is a type of health insurance plan that usually limits coverage to care from doctors who work for or contract with the HMO (Shay et al. 2015). Specialty services are in demand as the patient condition, requirements, and therapeutic management are dissimilar from common patients’ requirements. Patients from special population like pediatrics, geriatrics, and pregnant woman have altered physiology from general populations. The requirements of doses are different due to different pharmacokinetic and pharmacodynamic profile. Specialty healthcare services are a requirement but not a luxury. A specialty pharmacy is identified as a model of care and the type of services it provides to patients. Specialty pharmacies are different from traditional pharmacies in relation to disease management and patient care. Specialty pharmacies are dedicated to proficiently deliver medicines with special handling, storage, and distribution requirements. It requires standardized protocol that permits economies of scale. Economic and clinical outcomes can be improved by practicing the specialty pharmacies for patients with complicated disorders. Close contact and efficient management of disease is the important part of specialty pharmacy by providing patient education and encouraging medical adherence to make sure appropriate use of medication (Schwartz et al. 2010). SPS is also involved in handling high-cost specialty drugs in a sophisticated manner. In developed countries, specialty pharmacy is a service dedicated in filling of prescriptions for chronically ill patients require costly injectable, biotech, and oral medications. These specialty medications are useful for the treatment of diseases like human immunodeficiency virus (HIV), hepatitis C, rheumatoid arthritis, multiple sclerosis, etc. and require special handing. There is consultant clinic for patients, in which detailed patient history is documented regarding drug, food, pollens, and environmental allergies. Patients are also asked to provide medication history for the last 6 months, whether they are prescribed/administered any hormone products or herbal medicines. Furthermore, they are also inquired about using any nutraceuticals, vitamin supplements, and OTC medicines. For example, patient are checked for thyroid function and asked if they had undergone bone density scan or not. Daily activities like physical activities and daily average intake of water consumption are recorded. The dietary restraint regarding salt, carbohydrates, milk product, drug, and meat practiced by the patient is taken into account (Schwartz et al. 2010).

11.2

Case Study of a Specialty Pharmacy Service for Woman Clinics

For women, information regarding general medical exam, pelvic exam, and any abnormal Pap smear test is collected. Information regarding the menarche, the first menstrual period, and the last period is asked for. Information regarding the bleeding

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

183

in terms of day’s amount and presence of clots, pain, or cramping during periods and other times is also documented. Family history of cancer or osteoporosis is taken; how many pregnancies and living children and birth control methods along with mammograms are also collected. For a woman, flowing data is collected about hot flashes, dizziness, night sweat, headaches, sleeplessness, infrequent fatigue, stress, irritability, anxiety, depression, mood swings, confusion, memory loss, forgetfulness, muscle spasms, joint pains, backache, acne, new facial hair, frequent urinary tract infection, vaginal dryness, frequency urination, etc. (Hu et al. 2020).

11.3

Case Study of a Specialty Pharmacy Service for Men Clinics

For men’s health, pharmacists are there to assist patients and their doctors with compounded formulation of bioidentical harmony which may not be available in the open market. Specially hormone replacement therapy requires a pharmacist to work with patients and doctor in a customized manner. The pharmacist shall review personal medical history. The symptoms of patients is bothered with review of lab reports, and lifestyle and nutrition are discussed. Moreover, a compressive report is made for a patient and shall be discussed with the doctor who internally uses the information to counsel and update the patient to choose and comply with the treatment. Saliva and blood spot test kits are available for testing the hormone levels of the patients. The following hormones are tested to assist the adrenal function and reproductive health: cortisol, estradiol, estrone, progesterone, and testosterone. Consultation for man involves similar hormone level testing and discussing the health conditions of the patients, and the medical and social histories of men and women are collected by self-reported questionnaire including whether particular medication conditions exist in a patient or not, for example, high cholesterol, diabetes mellitus, high blood pressure, tobacco use, osteoporosis, benign prostatic hyperplasia, asthma, alcohol use, insomnia, erectile dysfunction, cancer, malnutrition, cancer, etc. Another important activity of specialty pharmacy service includes flowing areas of compounding of prescription as requested by physician, evaluation of adrenal/ thyroid dysfunction, dentistry, dermatology, wound care, palliative care, pain management, sports medicine, pediatrics, veterinary care, podiatry, and service regarding orphan medicines. There can be collaborations and consultations with doctors, dentists, and other healthcare professionals. The specialty pharmaceutical services aim at working closely with fellow healthcare providers and patients in a careful manner so that the healthcare delivery is optimized for best safety and outcomes.

184

11.4

A. N. Nagappa and J. Kanoujia

ADR Reporting and Pharmacovigilance

The World Health Organization had defined adverse drug reaction as “unwanted reaction of drug at normal dose used in humans for the treatment, diagnosis and prophylaxis of disease.” ADRs may occur after a single dose or extended administration of a drug or may be from the combination of two or more drugs. Drugs are exclusive bioactive molecule from biological, mineral, or chemical origin. They can interact with the biosystems and bring a change in the ongoing biological processes. For example, in fever, the body temperature elevated higher than the normal temperature causing discomfort in an individual. If it is not controlled, fever will cause severe damage to organs like the brain, kidney, and heart. There is a need to control the upsurge of body temperature. Commonly used drugs like aspirin or paracetamol are used for controlling high fever. The fall down of elevated body temperature provides relief from discomfort of the fever. Aspirin is also known for undesirable drug actions like gastric distress and bleeding tendency. Aspirin may speed up the pathway of lipolysis and glycolysis resulting in hyperpyrexia due to increases in the production of carbon dioxide (Kalaiselvan et al. 2015). Similarly, paracetamol can also cause liver toxicity, especially in older patients, resulting to damage of the liver. Paracetamol is known for its wide margin of safety in children and adults. It also affects many tissues and organs when taken overdose. Paracetamol may cause a feeling of nausea, abdominal ache, and tiredness. Long time exposure may lead to liver dysfunction with yellowing of the skin, confusion, and blood clotting problems. Paracetamol can also cause lactic acidosis, pancreatitis, kidney failure, and low blood sugar. Aspirin and paracetamol are used by a large number of people as OTC medicines and also prescription medicines for analgesic and antipyretic drugs. Several times people report with ADRs. It is necessary to document the ADRs in a systematic manner and review the signals periodically to know the status of safety of medicine in the population. Every medicine has a potential threat of ADR. It is the dose that determines whether the drugs administered is going to do beneficial effects or harmful effects. It is also important to distinguish the safety evaluation in clinical trials is very limited as the number of the subject in clinical trials is very small and the number of people who is going to use is infinite. Some of the ADRs occur in three episodes in 1 lakh or one million. In such cases, there should be a system of continuous observation of reporting and documentation when ADRs occur in the course of using the medicines. After World War II, the great Industrial Revolution spurred for economic growth and development. The development in science and technology heralded the era of modern living and management of health and other social needs. Especially in the Europe, there was an industrial revolution wherein several pharmaceutical industries were set up. The epidemic of diseases like bacterial infectious diseases started hunting the publics. In order to control the human suffering and death, there were needs of new drugs. Hence, the drug discovery and research became a prominent activity of the industry. Further, in order to patronize the activities, commercialization of drugs and health services was developed to support the nonstop activities.

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

185

Many new molecular entities were synthesized, for example, sulfa drugs, arsenic compounds, and various antibiotics like streptomycin and tetracycline were added to therapeutics. One of the main questions was regarding the safety of new drugs in human while used for treating diseases. Various animal models were established to test the safety of new drugs. Ultimately, it led to the founding of therapeutic index of individual drug which consisted of efficacy and toxicity together. There were many occurrences of adverse drug reactions (ADRs) while using these drugs. This led to mandating the necessity of watchfulness of long-term safety issues of the drugs in the humans. Drugs also caused variety of ADRs not only in patients who use them but also in children born with them, for example, thalidomide induced teratogenicity (Kalaiselvan et al. 2014). The public learned a hard lesson that the safe-looking drugs are not so safe and can cause genetic injuries and cancers. Watching and keeping an eye over the ADRs of drugs became a mandatory activity insisted by the government and drug regulatory agencies. The Government of India begins pharmacovigilance activity in the Department of Pharmacology in AIIMS, New Delhi. However, this activity was persuaded with an academic interest. Hence, it has remained confined among academic circles. In the last decades, the Government of India took keen interest and made a series of rules and regulations with an objective of serious monitoring of ADR profiles of used in prescription drugs. The GOI established the National Pharmacovigilance Programme of India (PvPI) and the Central Drugs Standard Control Organisation (CDSCO). The pharmaceutical industries were also interested in keeping an eye on the side effects of their company drugs under postmarketing surveillance in order to find and promote the off-label use of their products. This off-label marketing helped in expanding and enhancing the sale and value of the products. The regulators were quick to act and ban the promotion of off-label use of medicines. The law was amended that anyone who wants to promote medicines for particular off-label use are required to submit additional efficacy and safety data supporting the validity of off-label use of medicine (Sharma and Kellarai 2014; Rishi et al. 2012). Presently, it is established that human health is precarious and sensitive to chemical substances. The findings of institutions on drug safety in preclinical and clinical studies are not adequate, and it is very much important to keep watch and ward how drugs are causing injuries and damage to health. The therapeutically used drugs need to be subjected to pharmacovigilance. The new system of identifying, collecting, and documenting variety of ADRs of prescription drugs while they were utilized for therapeutic purpose is named as pharmacovigilance. The collected data was analyzed, and causality analysis was conducted to investigate the nature of toxicity. It was proved beyond doubt that the information regarding safety of the drugs is incomplete, and the outcomes of clinical trials are not just enough to declare as safe for human use. The pharmacovigilance is able to identify numerous surprising ADRs and was instrumental in establishing the toxicity which led to the banning of the product from the market (see Tables 11.1 and 11.2). The stakeholders of drug safety are government, drug regulators, healthcare providers, health insurance agencies, pharmaceutical industry, doctors, nursing

186

A. N. Nagappa and J. Kanoujia

Table 11.1 Therapeutic drugs causing serious hazards to the public S. no. 1 2

3 4

Drugs Immunoprin (thalidomide) Brufen (ibuprofen) Grepafloxacin (Raxar) Indoprofen (indomethacin)

5

Butazolidine (phenylbutazone)

6

Toradol (ketorolac)

7

Vioxx (rofecoxib)

8

Bextra (valdecoxib)

9

Permax (pergolide) Nimulid (nimesulide)

10

Therapeutic category Immunomodulator Nonsteroidal antiinflammatory drug (NSAID) Fluoroquinolones Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Dopamine receptor agonist Nonsteroidal antiinflammatory drug (NSAID)

Type of toxicity Teratogenicity, multiple myeloma Hepatotoxicity, jaundice

Year withdrawn 1961 1968

Cardiac repolarization, QT interval prolongation Gastrointestinal bleeding

1999

Off-label abuse, hematologic toxicity

1985

Hemorrhage, renal failure

1993

Myocardial infarction and stroke

2004

Stevens-Johnson syndrome

2005

Heart valve damage

2007

Hepatotoxicity

2011

1983

Table 11.2 Drug-induced toxicity S. no. 1 2 3 4 6 7 8 9 10 11

Drugs Abacavir Acetazolamide Aminoglycoside Angiotensin-converting enzyme inhibitors Amphetamine Chloroquine Dexamethasone Doxorubicin Methotrexate Ximelagatran

Toxicity Myelotoxicity Myelotoxicity Nephrotoxicity Nephrotoxicity Neurotoxicity Methemoglobinemia Osteoporosis Aplastic anemia Neurotoxicity Hepatotoxicity

homes, corporate hospitals, pharmacists, nurses, and patients. The Government of India (GOI) has an obligation to its citizen and is accountable for patient safety in general in order to safeguard patient safety. The GOI has established drug control

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

187

department and professional councils and enacted the rules and regulations to ensure satisfactory administration and management of safe use of medicines to the public. The Government of India in order to rationalize the healthcare delivery has established the National Health Council. The documentation of patient safety is carried out by the Pharmacovigilance Programme of India (PvPI). The GOI is aware that all Allopathic, Homeopathic, and Ayurvedic drugs do have the potential to inflict injuries if dose exceeds safety limits. Prescription drugs are to be used under the direct supervision of registered members of respective councils; for example, allopathic medicine should be used and managed by respective qualified doctors, nurses, and pharmacists of allopathic medicine. However, prescription of Homeopathic and Allopathic medicine by Ayurvedic practitioner should be considered as quackery. The pharmaceutical industry is obligated to provide freedom from injury to the public while marketing them. The healthcare professional should work in a team to ensure the patients are not harmed while using the medicines. These are being technical products and are capable of causing damage to the internal organ and to the health of the patients (Jeetu and Anusha 2010). Doctors, nurses, and pharmacists have to causious while prescribing prescription drugs used for the treatment of disease. The punch line of practice of medicine is by principle of no harm by the treatment itself. Drugs are unpredictable in their actions as for safety is concerned. The healthcare professional should access the risk-benefit ratio while prescribing; in case the benefit overweighs, then only drug can be prescribed. The public comprising of patients and health consumers should understand not to play with the prescription medicine and health by indulging in selfmedications. They should keep themselves away from the prescription medicine and observe strict abstinence from prescription medicines. The public should change their attitude of quick fix of diseases and remedies and should overcome the habit of overdependence on symptomatic relief. Self-medication is highly dangerous as it is the outcome of the frustration of patients who try to overcome the suffering by hook or by crook. This attitude is against the principle of health management which can lead to drug-induced diseases. Patients, public, and health consumers should not play with prescription medicine and succumb to ill health. Drugs which have caused and induced organ damage and disease are listed in Table 11.2. For example, abuse of pain killers (NSAIDS) causing nephrotoxicity and leading to chronic renal disease is a common cause of renal damage and chronic kidney failure. The abuse of steroids as beauty-enhancing aids can lead to systemic toxicity of steroids leading to osteoporosis, cholestasis jaundice, and liver toxicity. Drugs like aspirin and acetaminophens which are considered as safe drugs and are given the status of over-the-counter drugs have the potential to cause severe damage (Talbot and Nilsson 1998; WHO 2002). These are also proved to be dangerous when someone tries to commit suicide by overdose. Hence, whether it is over-the-counter (OTC) or prescription drugs, it should be used under the guidance of registered pharmacist. It is also noticed the abuse of psychotropic drugs leading to psychological/ physical dependence is on the rise. Health consumers who are under stress has found out by indulging in psychotropic substances they are able to get a temporary relief from the stress. They also indulge in abuse of alcohol. Drug abuse causes slow

188

A. N. Nagappa and J. Kanoujia

harmful effect on the health and damaging mental health of the person but also his/her family. The social community gets deteriorated. Usually, public thinks that most medicines are harmless and are safe for use. Public believes drugs have a scientific background and have been tested for safety. This overconfidence is the major driving force for self-medication by the public. The GOI has established legal premises to ensure public health and patient safety from prescription drugs, psychotropic drugs, alcohol, and OTC medicine. However, the enforcement of many of laws has remained nonstarter, and the patient safety remained at ground zero. For example, the sale of prescription drugs across India is banned to the public without a prescription. In reality, we soon realize that any prescription medicine can be procured without a prescription at drug stores. This law is ignored by pharmacist and public for mutual convenience at the risk to individual and public health. There is a severe conflict of interest playing a role in this violation of pharmacist and public; for pharmacist, it is the trade and profit, and for patients, it is the convenience of avoiding the hospital visit. Even the pharmaceutical industry does not object this wrong happening. Industry thinks it is their right to sell all the medicines they have manufactured. As a result of this, pharmaceutical industries are pushing manufactured products to doctors, pharmacists, and nurses to write more prescriptions and make the people to consume more drugs in the absence of accountability. Healthcare providers are having a free hand in prescribing and selling prescription medicines to the patients due to the lack of accountability, transparency, and accountability. The worst part is that many will buy prescription medicine in bulk from pharmacies and sell this medicine in rural places. Most of them are quacks and unauthorized medical practitioners who practice in the rural area. They often sell steroids and other dangerous medicines to impress patients to the public. Cross prescription is another problem in which we find many Ayurvedic doctors writing allopathic medicine and vice versa. This has resulted in the widespread abuse of prescription medicine by the public as well as healthcare professionals in the name of self-medication (Coulter 2000). The professional councils have utterly failed to establish professional standards and practicing norms, for example, the Pharmacy Council of India (PCI) which grants license for registered pharmacist and authorizes the registered pharmacist to practice the pharmacy profession. The main effort of pharmacist is to protect the public from ill effects of drugs and give appropriate health education. However, pharmacist is not at all doing any services but focused on selling prescription medicines to the public by themselves or whenever they are asked by the public. Pharmacists consider that over-the-counter sale of medicines is their right and main source of income as well as indulging in selling of prescription medicines illegally regardless if they violate the law of the land. It is also stated in the Pharmacy Act 1950: no pharmacy should operate without registered pharmacist. Due to the lackadaisical attitude of the regulators, registered pharmacists are renting out their certificates for second income, and thus, the law of the land looks foolish and useless after observing this existing practice. Due to the lack of infrastructure and interest, the pharmacovigilance activities have remained less productive in India. The stakeholder’s involvement and

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

189

contribution are not encouraging due to various factors and conflicts of interest. For example, if a doctor comes across serious ADRs, he is upset as he thinks the ADRs have happened due to negligence during the treatment by her/him. That’s why she/he wants to underplay and suppress the occurrence of ADRs. Similarly, the hospitals are cautiously engaged in letting the information of serious incidents of ADRs. The reason is reputation of the hospital is at stake and also the public anger which may be violent resulting in damage to hospital equipment and staff. In reality, ADRs may not be caused by doctor or hospitals, and it might be due to the drug itself. Hence, it is necessary to provide a congenial atmosphere (Sleath et al. 1997). Clinical trial-based approvals of drugs are limited to efficacy and not to safety. This is because during clinical trials, the number of humans getting exposure to drug is limited. However, when the drug is licensed and being used in the open market, a large number of patients gets exposed to the new drug. It is also true everyone may react differently and likely to show different kind and degree of responses. There are many evidence where variations in genetic predispositions of ADRs are reported. Prescription medicines are used for several years by patients especially in chronic conditions and diseases. Drug-specific toxicity is well identified, and appropriate risk benefit analysis guides the prescribing for patients. Table 11.4 lists drugs which are proven to cause DNA damage leading to variety of cancers in animal studies; hence, there is always a danger of getting cancer due to DNA damage during the course of treatment. For example, a timolol/paracetamol and antidiabetic drugs/antiviral drugs need to be used for a long term; hence, there is a need to observe for cancer progression among patients using the above drugs. Hence, the Government of India has made mandatory to carry out pharmacovigilance of all prescription medicines marketed by each individual manufacturer. The above knowledge on genotoxicity leads to carcinogenicity into the campaign in the public health program on par with tobacco-related hazards (Table 11.3). There are a lot of mistakes and errors creeping in the reported areas. There is necessity of guidelines which are highlighted in Figs. 11.1 and 11.2. There needs to be systematic collection, analysis, and documentation of reported ADRs. All the ADRs reported are scrutinized by strict vigilance protocol given in the algorithm in Fig. 11.3. The reported ADRs are analyzed by casualty scales, Naranjo scale, and WHO scale. Thus, scored ADRs are documented at a national level and periodically reported to the WHO Centre for ADR reporting in Uppsala, Sweden. Gradually Indian economy is picking up positively, and all-round development including health sector is improving in the future. The pharmaceuticals shall be used more rationally. This is because the government and regulators are taking keen interest in ensuring maximum patient safety and avoidance of drug-inflicted injuries. Pharmacovigilance practice is supported by the central government, and all the industries are made to submit pharmacovigilance data every quarterly to vigilance center. The analysis of reports is shared with government agencies and Uppsala Pharmacovigilance Center (see Fig. 11.3). Such a change in scenario is stimulated by awareness among the government, stakeholders of healthcare provision, and public which has stimulated the increased reporting of ADRs. Drugs are likely to be used

190

A. N. Nagappa and J. Kanoujia

Table 11.3 Genotoxicity of prescription drugs in animals S. no. 1

Drug Cidofovir

Therapeutic category Anti-human immunodeficiency virus (anti-HIV)

Organ affected Zymbal gland carcinoma and mammary carcinoma Cardiovascular thrombotic, cancer of the adrenal medulla Hematopoietic carcinoma and uterine adenocarcinoma Thyroid cancer

2

Celecoxib

3

Dexrazoxane

COX-2 selective inhibitor, nonsteroidal anti-inflammatory drug (NSAID) Cardioprotective agent

4

Exenatide

Incretin mimetics (reducing the sugar level)

5

Fluoxetine

Antidepressant

Cancer, breast

6

Glimepiride

Antidiabetic (type 2 diabetes)

Pancreatic islet cell adenoma

7

Insulin glargine

Hormone

Fibrous histiocytoma

8

Paracetamol

Analgesic and antipyretic

Liver and bone marrow cancer

9

Pantoprazole

Proton pump inhibitor

Liver adenoma, thyroid cancer

10

Pioglitazone

Antidiabetic drug

11

Rasagiline

Irreversible inhibitor of monoamine oxidase-B

Urinary bladder transitional cell tumors Lung cancer

12

Timolol

Antihypertensive

Pulmonary tumors, uterine polyps

13

Tacrolimus

Immunosuppressive drug

Lymphoma

Status Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market Still in the market

rationally as transparency and accountability factors are implemented. Hence, instead of earning money just by sales volume, healthcare providers start getting paid for the quality of service they provide to public. Such a scenario is already in existence in countries like Australia, New Zealand, and Japan. Healthcare providers are assessed for the productivity of healthcare services rather than the services without any accountability. It is very necessary to practice other services like

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

191

Fig. 11.1 How to detect the ADRs Fig. 11.2 How to report the ADRs

physicians, pharmacists, and nursing care. There shall be a system of identifying not only the wrong practitioner but also ethically standard practitioner. The ethical standard practitioners are rewarded, whereas the wrong doers shall be punished.

192

A. N. Nagappa and J. Kanoujia

Fig. 11.3 The flowchart of pharmacovigilance systems

11.5

Pharmacy Practice in Pediatrics

The basic principles of pharmacy practice in pediatrics are to accept the fact that a child is not a small adult. Children are different from adults in terms of pharmacokinetics, dose response, and pharmacodynamics. In general, it is reasonable to expect children are having larger volume of distribution in comparison to young adult patients. They also vary in age-related metabolism and clearance rate. It is also important to keep in mind that demographic profile related with pediatric patients often can be misleading. One should be critical regarding the misconception of the age of pediatrics – end by the age of 18 years. In general, if the patient is less than 40 kg, then he/she may be given pediatric dose depending on the weight. While deciding the dose for pediatric patients is based on body surface area. The pharmacist should be clear about the scale of weights, for example, kg/pounds. If the body surface area is not provided in a written form, then there will be errors; while calculating a dose for a child, one should be strict to the rule that dose calculated for a child not to be more than adult dose. Pharmacist should always be careful regarding administration of medicines in children. It is very difficult for a patient of 2 years old to swallow a tablet or capsules (Pediatric Pharmacy Practice Guidelines 1991). Many a times, it is not possible to crush the tablet for the sake of administration, children are sensitive toward the taste of the products, and a pharmacist should resort masking technics, adding taste masking agents and flavoring agents, and psychological technics like inducement and distraction technics. Children usually cooperate after some initial denial. Pharmacist should also understand children cannot drink

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

193

large volumes of medicines; hence, the pharmacist should keep the liquid orals as small as possible, so that child can swallow. Unlike in adults, monitoring of the health condition of children can be challenging as they cannot communicate the problem they are facing or understand what the pharmacist want to know. Pharmacist with proper experience and skills can approach, communicate, and understand regarding the patient monitoring issues (Buck et al. 1993; Shaller 2004). Pharmacy practice in pediatrics requires more skills than evidence, for example, primary data and evidence-based literature to accept or refuse an approach to a patient, doses to be used, and decision about regimen of dose for all these questions. There is no direct information available; pharmacist has to decide and act using his/her knowledge and skill gained by the previous experience. Pharmacy practice pharmacist should also have a logical bases about the clinical judgment made and explain to the parents to remove their anxiety and build trust of their capability about the course of treatment given to their child.

11.6

Interacting with the Pediatric Patients

Pharmacist should not be frightened just because she/he is not an expert in handling children. Pharmacist should remember that she/he is an a expert in pharmacotherapy and applying the knowledge of basic differences between pediatric and adult patients can be basis of confidence. Furthermore, using the knowledge and available resources will make the job easy and stress-free for the practice of pediatric pharmacy. Thus, resources are suggested to be useful in Table 11.4. Pediatric pharmacist should be careful about routes of administration. She/he should try to avoid injections and try to reduce drug-related pain issues while administrating the drug and during blood collection. One can apply local anesthetic cream or injection admixture with lidocaine. One should also be careful in assessing the diseases which are different from adult patients, for example, most of the pneumonia cases in children are triggered by viruses and should not be mistaken as bacterial infection and treated with antibiotics (Mărginean et al. 2017; Shin and White-Traut 2005).

11.7

Pharmacy Practice in Geriatrics

Geriatrics is the branch specifically emphasizing on healthcare of aged people. Prevention and treatment of old-aged diseases are the prime goals of geriatrics pharmacy practice (Fig. 11.4). Pharmacists are committed to optimizing drug therapy for individual patients and improved outcomes with cost control; pharmacist empowered with clinical and information technology skills is competent to provide services in geriatric patients in collaboration with doctors and nurses. Pharmacists can identify patients with risk for a given disease and plan pharmaceutical care for a patient. In this view, she/he can identify unnecessary healthcare

194

A. N. Nagappa and J. Kanoujia

Table 11.4 Resources commonly used in pediatrics Resource Clinical pharmacology

Advantage(s) Accessible online

Disadvantage(s) Requires subscription

The Harriet lane handbook

Good reference for pediatric diseases

Drug dosing information is limited

Children’s Hospital of Philadelphia: Extemporaneous formulations for Oral administration

Includes extemporaneous formulation data sheets for each preparation that detail the dosage form, step-by-step preparation, storage conditions, special instructions, and expiration dates, well referenced Provides drug dosing, monitoring, and limited compatibility information for medications for neonates

Not updated or published since 2003, may be difficult to obtain

NeoFax

Lexi-comp online for pediatrics

Nelson textbook of pediatrics

Pediatric injectable drugs: The teddy bear book

Updated frequently, provides reference for drug dosing, available for handheld electronic devices Provides in-depth overview of pediatric diseases and stages of development

Dosing and rates of intermittent and continuous intravenous

Updated annually, may not provide dosing recommendations for medications used infrequently in neonates, provides dosing information for neonates exclusively Requires subscription, lacks access to tables available in the book format Updated periodically, provides limited drug dosing information

Updated periodically, no electronic form available

Citation or contact information www. clinicalpharmacology. com Robertson J, Shilkofski N, eds. The Harriet lane handbook: A manual for pediatric house officers, 17th ed. St. Louis: Mosby, 2005 Jew RK et al. Children’s Hospital of Philadelphia: Extemporaneous formulations. Bethesda, MD: American Society of Health-System Pharmacists, 2003

Young TE, Mangum B. NeoFax 2007, 20th ed. Montvale, NJ: Thompson Healthcare, 2007

www.crlonline.com/ crlsql/servlet/ crlonline

Kliegman R, Behrman RE, Jenson HB, eds. Nelson textbook of pediatrics, 18th ed. Orlando, FL: W.B. Saunders, 2007 Phelps SJ, Hak EB, Crill CM, eds. Pediatric injectable drugs: The teddy bear (continued)

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

195

Table 11.4 (continued) Resource

Advantage(s)

Disadvantage(s)

medications, good reference for concentrations, well referenced Poison control center

Red book

Authoritative information in toxicological emergencies Reported by the American Academy of Pediatrics Committee on infectious diseases, provides disease and treatment option overviews for various pediatric infectious diseases

Fig. 11.4 Geriatric patients at risk

Telephone access only

Provides limited drug dosing recommendations

Citation or contact information book, eighth ed. Bethesda, MD: American Society of Health-System Pharmacists, 2003 1–800–222-1222

aapredbook. aappublications.org or red book: 2006 report of the committee on infectious diseases, 27th ed

196

A. N. Nagappa and J. Kanoujia

expenditures and avoid issues associated with medications. She/he can also aim at promoting quality of life for the geriatric patients. It is true that most of the elderly patients suffer from age-related conditions and are usually on prescription medicines. In addition to this, they will be using nonprescription medications for minor ailments they suffer from. They will be using OTC medicines for constipation, deficiency of sleep, and other conditions to boost energy (Woelfel et al. 2011). The aim of the geriatrics is to cure, palliate, as well as improve quality of life. Quality-of-life considerations include daily living activities, cognition, and freedom from depression, active participation in social activities, support systems, and general health perception. It is also important to work on the prevention of drugrelated ADRs in aged patients. It is usually observed geriatric patients are usually taking more than five medications for a variety of conditions and symptoms. Sometimes the medication may be excessive or unnecessary, which make the patients to face a danger of ADR. It is very important to review the prescription and balance between excessive and unnecessary medications they are using, which may benefit the patients. More number of medications in geriatrics is attributed to aging population, complex drug therapy, multiple prescriber and pharmacy, psychosocial factors, and ADRs. Usually, patients with chronic diseases shall be prescribed with multiple medications by different doctors for different conditions. The poor communication between patient and healthcare providers increases the complexity. Doctor always try to add drugs in prescription instead of discontinuing if drug is not required. It is also observed that regular monitoring for potential harm is not carried out in the conventional healthcare delivery. One can spot many medications with no proper indication, duplication of therapy, drug interaction, and improper low or high doses. Many patients indulge self-medication with OTC, herbals, and supplements. This tendency is very much aggravated by direct-to-consumer advertising and off-label marketing campaigns (Keys et al. 2004). Aging population has an increased incidence of chronic conditions like asthma, arthritis, Alzheimer’s disease, diabetes, hypertension, heart failure, ischemic heart diseases, and urinary problems. Due to aging and decrease in organ functions, it leads to altered pharmacokinetic of ADM (hepatic) and (renal clearance) profile. Similarly altered blood pressure and hemodynamics are age-related changes that need to be observed for the risk of ADR. In optimization of drug therapy in geriatric by taking the medication history and evaluating risk/benefits, one should raise the question regarding clear indication of the medicine prescribed. All the OTC medication, vitamin supplement, and herbals used by the patients are to be reviewed, such as checking for allergies and ADR to medication, medicines used by patients, patient social habits of drinking alcohol, tobacco use, or any other recreational drugs. Flu and pneumococcal immunizations that have been taken should also be checked. One should also make a medication diary and update once in a week after evaluation. Any patients need to discontinue an unnecessary medication. One should also look for nonpharmacological approaches to mitigate the conditions. If it is also possible, one should try to avoid or minimize drug interactions by altering

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

197

Table 11.5 Examples of the prescribing cascade in the elderly patients Preliminary therapy Glitazone NSAID Thiazide diuretics Cholinesterase inhibitor Metoclopramide

Adverse effect of preliminary therapy Onset of heart failure, edema Issue of high blood pressure Hyperuricemia as an adverse effect Urinary incontinency Parkinsonian-like symptoms

Subsequent therapy Diuretic Antihypertensive drugs Treatment for gout Anticholinergic Anti-Parkinson drugs

Table 11.6 Examples of drug-food interactions in the elderly patients Drug Warfarin Benzodiazepine Potassium-sparing diuretics, ACE inhibitors Statin

Food Food rich in vitamin K Alcohol Foods rich in potassium Grape juice

Digoxin

Diet rich in fiber

Concern Reduction in anticoagulant effect CNS depression Hyperkalemia issue Increased risk of hepatotoxicity, rhabdomyolysis, myopathy Decreased treatment effect

Table 11.7 Examples of drug-disease interactions in the elderly patients Drug Phenylephrine NSAIDS, aspirin Antihistamines, anticholinergics, oxybutynin Antipsychotics, metoclopramide Anticholinergics, TCAs, calcium channel blockers

Disease Hypertension Ulcer Urinary Parkinson’s Constipation

Concern High blood pressure Aggravation of ulcer Decreased urinary output Worsening of Parkinson’s Aggravation of constipation

Table 11.8 Examples of important drug interactions in the elderly patients S. no. 1 2 3 4

Combination of drugs Combinations of drugs with excess anticholinergic effects Digoxin and quinidine/diazepam Warfarin and aspirin/NSAIDs, ABX ACE inhibitor in combination with potassium supplements

Risk Risky and should be avoided Digitalis toxicity Increased risk of bleeding Increased potassium level

timing of the doses. Whenever new medications are prescribed, one should start with low dose, and after stabilization, one can take the prescribed dose. All this is possible if the patients are continuously monitored (Odegard et al. 2007). Tables 11.5, 11.6, 11.7, and 11.8 explain the prescribing cascade, drug-food interactions, drug-disease interactions, and drug interaction in elderly patients.

198

11.8

A. N. Nagappa and J. Kanoujia

Altered Pharmacodynamics

The sensitivity toward certain drugs in elderly person is associated with age-related results of the risk of adverse drug reactions: • Anticoagulants and hemorrhage (e.g., in combination with NSAIDs, salicylates). • CNS depressants like benzodiazepines cause confusion, sedation, delirium, and agitation. • Hemorrhage and anticoagulants in combination with NSAIDs and salicylates. • Combination of antihypertensive medications with alpha-blockers leads to orthostatic hypotension. • Anticholinergic drugs resulting in blurred vision, constipation, confusion, and urinary retention issues.

11.9

Women During Pregnancy

Pregnancy leads to several physiological changes which may alter the effects of medicines that mandate careful monitoring of the patients. Physiological change begins mainly in the first trimester and reaches peak in the second trimester (Table 11.9). For example, there will be an increase by 30–50% in maternal plasma volume, cardiac output, and GFR which affect the lowering concentration of renal cleared drug. During pregnancy, an increase in the body fat also increases the volume of distribution of lipophilic drugs. There is significant decrease in serum albumin concentration which enhances the volume of distribution of highly fat-bound drugs. There is an increase in the hepatic perfusion which increases the excretion drugs by liver clearance. The placenta is an organ connecting the mother to the child, known for preventing drugs crossing the barriers and preventing drugs affecting the fetus. Drug factors which affect placental transfer are lipid solubility, molecular weight, and degree of protein binding. It is important to note that fetal pH is slightly acidic than the maternal pH leading to entry of weak organic bases more easily across the placenta. The weak organic base becomes ionized, gets trapped in the fetal circulation, and is less likely to come back to maternal circulations. This may lead to situation of extended exposure of more drugs to the fetus in more concentrations of drug. This may interfere with organogenesis which is in the active growing phase. Increased concentration of a drug may also interface with the growth mechanism and lead to effects like teratogenicity and malformation of organ development. The best approach is to avoid using any drugs during pregnancy and lactation (Albassam and Awad 2018). The pharmacist must weigh a risk and benefits during pregnancy and lactation, despite of the fact that administered drug is going to interfere the growth of the child and women are using medications for obvious reasons of health during pregnancy. Moreover, 50% of pregnancies are unplanned, and many a time, they are exposed to medication before they learn about their pregnancy. The most common medications

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

199

Table 11.9 Phases of embryonic and fetal development Phase of development Implantation and pre-differentiation

Stage of pregnancy 0–14 days after conception (14–28 days after last menstrual period)

Organogenesis (embryogenesis)

From day 14 until the ninth week after conception (from day 28 until the 11th week after last menstrual period) After the organogenesis and until birth

Fetogenesis

What happens during this phases of development All or none period, very little contract between the blastocyst and the mothers’ blood cells are pluripotent; capacity to repair a damage remains; cells are fragile at this moment; if too many are killed, a miscarriage will occur before the pregnancy is detected Organs are formed, most critical period for structural anomalies organs are formed at different times; period of sensitivity for a potential teratogen could be different for each organ

Potential teratogenic effect Spontaneous abortion or miscarriage Even if stopped during this period, prolonged half-life drugs could cause organogenesis problems

The fetus grows and organs begin to function (e.g., kidneys are formed during organogenesis, but glomerular filtration begins during fetogenesis), active cell growth proliferation, and migration (e.g., CNS)

Fetal growth retardation, functional deficit (e.g., renal insufficiency, pulmonary hypertension, neurologic impairment)

Major or minor structural anomalies

women use during pregnancy and lactation are multivitamins with minerals like calcium and iron, analgesics, antacids, antibiotics, and antiemetics. They also use OTC medicines for cold and flu along with laxative to relieve constipation. In case if they have asthma, they need to use anti-asthma medications which include beta-agonist like salbutamol and corticosteroids like beclomethasone. However, they can use inhalers instead of oral/iv injections, which may not cause much harm than oral administration. If women have a fungal or bacterial skin infection, they shall be using antifungal, antibiotic, and corticosteroid topical ointments. One should be cautious about systemic toxicity of topical administration of corticosteroids (Lyszkiewicz et al. 2001). It is happy to note that the actual risk of birth defect from drug exposure is small and drug-induced teratogenicity is of major concern. Congenital anomalies due to exposure to prescription medicines and OTC in the normal usage are less than 1%. Congenital anomalies are usually of genetic origin and maternal infections. Pregnancy is classified into three trimesters of 13 weeks or 91 days. Depending on

200

A. N. Nagappa and J. Kanoujia

organogenesis or growth, it is divided into three phases, first phase being the implantation and pre-differentiation, the second phase embryogenesis in which organogenesis happens, and the third phase the fetus genesis. Most of the birth defects due to exposure to drug happen during embryogenesis. Teratogenicity is a modified normal embryonic and fetal development. It can lead to functional deficit, cancer, structural anomalies, spontaneous abortion, stillbirth, and growth retardation. Teratogenicity is the effect of drugs on embryogenesis/fetal development. It can manifest as structural abnormalities, growth retardation, cancer, and stillbirth and spontaneous abortion. It can also manifest as variety of functional deficiencies in the newborn need to establish corelation between teratogenicity and a drug used. The drug is said to be teratogenic if the observation regarding particular strength of the drug is going to produce such defects. Similar effects also observed in animal studies confirm the correlation. An explanation based on pharmacological effect of the drug leading to biological possibility of organ defect pinpoints the suspicion of the drug. They should have a dose-response relationship indicating the teratogenic effect. Finally, such cases reported in the population confirm the teratogenicity of the drug. It shall be observed while using medication during pregnancy and fall in the episodes soon after medication is discontinued. One of the important functions of pharmaceutical care is to fix desired outcome and take all precautions of treating the maternal or fetal conditions and taking care to minimize the risk to neonate of the teratogenic effects. It is very unethical to perform classical randomized clinical trials of effect of medication on pregnancy and effect of drugs on growing child and neonates. Hence, evaluations of safety of medications during pregnancy and lactation must be relied upon postmarketing surveillance and pharmacovigilance. However, it is sensible to perform preclinical studies using animals which are indicative of teratogenic effect. However, such effect may not happen in humans due to variations in species. It is very much important to identify high-risk medications that are likely to cause congenital anomalies and avoid such drug entering to the market (Schrempp et al. 2001). One of the biggest challenges in pharmaceutical care is counseling pregnant women and other caregivers regarding the medications prescribed for use. Many a time, due to contradictory reports about the ADRs of a drug during pregnancy, it becomes very hard to convince the patients and the caregiver about possible risk of the medication. It is also a cause of concern and anxiety for many women as well as for their healthcare providers if the uncertainty of drug effect causes congenital problems in the newborn. Data based on medication used during pregnancy is limited and sometimes clashing. Pregnant women may overestimate their risk associated with medication and ignore the health problems associated with medicating with new medicines. Healthcare providers cannot properly understand and guess reasonably. Outcomes of the pregnancy are influenced by maternal health, lifestyle, and history before conception, and adverse pregnancy outcomes like premature birth, birth defect, and low birth weight are the major health concerns. One of the causes may be due to the late start in prenatal care. To improve the pregnancy outcomes, the goals of

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

201

preconception care should include health promotion with evidence-based screening and timely intervention. Pregnancy outcomes can be improved by following the strategies that include taking folic acid; avoidance of smoking and alcohol; monitoring and management of diabetes, epilepsy, and hypertension; and regular screening of HIV and other STDs. Proper vaccination, maintaining a healthy body weight, and taking folic acid play a vital role in the prevention of neural tube defect. It may also be involved in the reduction of many congenital defects involving limb deformities, cardiovascular issues, urinary malformation, and oral clefts. It is very important to advise every woman of childbearing age about folic acid and maternal health. Women should take 5–8 mg of folic acid every day. In the first month before pregnancy and subsequent 3 months, women become deficient in nutrition. They should be taking folic acid 4 mg every day without fail, especially women on carbamazepine and valproic acid, and should be advised not to miss. One of the other causes for concern is iron supplements, if women are having hemoglobin less than 11 mg per 100 mL during first and third semesters and 10.5 mg per 100 mL during the second trimester. Common symptoms of iron deficiency include fatigues, palpitations, and weaknesses for physical work and caching up infections frequently. Fetal risks include premature birth with low birth weight and perinatal death, decreased iron supplementation, and maternal anemia during the child delivery.

11.10 Pregnancy Influence and Issues The preference should be given for nonpharmacological intervention instead of drug treatments. There should be risk-benefit analysis before administering any drug. If it is possible to postpone treatments after childbirth or during or after pregnancy and breastfeeding, it should be considered. 85% of pregnant women suffer from nausea and vomiting. It usually initiates during the fifth week of gestation and continues till the 20th week. Peak symptoms are obscured between 10th and 16th weeks, including hyperemesis gravidarum in which there will be an uncontrolled vomiting leading to weight loss, dehydration, electrolyte imbalance, and ketone urea. Nonpharmacological preventive (Table 11.10) measures for management of hyperemesis gravidarum include lifestyle modifications such as having adequate rest with dietary changes like small and frequent meals, avoiding water during meals, avoiding fatty food, and using some of the nondrug therapy like ginger. Drug therapy including vitamin B6 with doxylamine is a first-line therapy. Approximately, 40% of pregnant women suffer from constipation; in this case, nondrug therapy should be used along with consoling them regarding the importance of fiberrich diet and adequate fluid intake. In addition, practicing exercise and avoiding long time in the toilet can be beneficial. Among drugs like bulk-forming laxative, psyllium and calcium polycarbonate can be used; if the above method fails, one should consider using emollients or osmatic agents and stimulant laxatives which can be used for short term. During

202

A. N. Nagappa and J. Kanoujia

Table 11.10 Nonpharmacological and pharmacological recommendation for various conditions in pregnancy Condition Heartburn/ GERD

Nasal congestion and rhinitis

Nonpharmacological Eat small and frequent meals; remain upright after eating Elevating the head of the bed Avoiding smoking, chocolate, coffee, fatty foods, and peppermint Rest and increase fluid intake

Humidified air

Nasal saline irrigation

Urinary tract infections

Avoid irritants and known allergens Raising the head of the bed at 35–45
Cranberry juice

Vulvovaginal candidiasis

Ranitidine Omeprazole, sucralfate, and metoclopramide

Paracetamol

Oral decongestants should be avoided during the first trimester of pregnancy, may cause fetal gastroschisis Use after the first trimester, pseudoephedrine and topical decongestants Use corticosteroids for chronic nasal rhinitis

Antimicrobial therapy should be for E. coli infection Safe drugs include penicillin, cephalosporin, and nitrofurantoin Avoid trimethoprim and sulfamethoxazole Bacterial vaginosis Oral metronidazole or clindamycin Vaginal creams of clindamycin should be avoided During lactation, vaginal formulations are preferred Topical azole therapy for 7 days Oral fluconazole should be avoided but can be used during breastfeeding Penicillin G

Group B streptococcus

Preeclampsia

Pharmacological Calcium or magnesium containing antacids

Delivery of the child

Ampicillin Clindamycin Intravenous magnesium sulfide Methyldopa, nifedipine, and labetalol should be avoided. ACEI, ARBS, or renin inhibitor (fetopathy) atenolol (intrauterine growth restriction) (continued)

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

203

Table 11.10 (continued) Condition

Nonpharmacological

Diabetes

Mastitis

Breast candidacies

Cold or warm compresses Frequent breastfeeding Breast pumping Antifungal treatment to both mother and child

Pharmacological Low-dose aspirin useful in preventing preterm birth, preeclampsia, calcium supplements, and fetal neonatal death 1 gm per day for preventing preeclampsia Insulin glyburide metformin Anticoagulation Low molecular weight heparins Warfarin used in the second trimester and early third trimester Paracetamol Ibuprofen Naproxen Painkillers like paracetamol can be used to relief pain

lactation, bulk-forming emollients and osmotic laxatives can be used safely. However, castor oil and mineral oils should be avoided as they can be the reason for uterine contractions and impair the absorption of fat-soluble vitamin A, vitamin D, and vitamin K.

11.11 Management of Cancer In the management of side effect of cancer therapy, it is very important to keep in mind that a cancer patient suffers not only from cancer but also due to side effect of cancer therapy. Patients are under huge psychological stress with anxiety due to side effect of the anticancer therapy. A systematic approach of handling the patients and providing motivation to patients plays a significant role in reducing stress and anxiety. A systematic approach involves recognition of the side effects and application of preventive strategies to minimize the consequences of side effects by anticancer drugs. Clinical pharmacist should also engage in patient counseling and discuss in detail the side effects so that patient understands and cooperates during the treatment (Jaehde et al. 2008). Side effects of cancer therapy are given below.

11.11.1 Side Effects or Consequences of Cancer Therapy 1. 2. 3. 4. 5.

Hematological Gastrointestinal Hypersensitivity Renal toxicity Bladder toxicity

204

6. 7. 8. 9. 10.

A. N. Nagappa and J. Kanoujia

Hepatotoxicity Nervous system toxicity Gonad dysfunction Extravasation Infusion-related reactions

Another side effect which affects the quality of life of patients is cancer induces nausea and vomiting. In this, each patient is evaluated for emetogenic effects and the pattern of the chemotherapeutic regimen.

11.12 Prophylactic The pharmacist should apply the antiemetic regimens. It should be understood that each patient is different as well as the estimation of the threshold of the patient for nausea and vomiting. After getting some ideas of the patient, she/he can decide upon which antiemetic is suitable for individual patients. Pharmacist can suggest the chronological order of medicines that can be administered to the patients. She/he should also be sensitive to the cost of the medicines. The pharmacy practice can be divided into three sections like before the prescription, during the prescription, and after the prescription. Before the prescription, the pharmacist reviews the clinical trial data, formularies, and drug information. Pharmacists due to their background in medicines have great influence on the formation of implementations of drug-related policies in hospital. They greatly translate information from national formularies into a hospital formulary. The formularies prepared by pharmacist in the hospital are to be referred by the doctors for prescription of appropriate medicines. Pharmacist should also be an active member in clinical trials at different levels. Oncology pharmaceutical care plans involve reviewing of cancer therapy and taking an account of various side effects of anticancer drug administered and also assessment of complication of cancer, for example, pain management. The pharmaceutical care plan also looks into the comorbidities and also involves them in the pharmaceutical care plan (Cruz et al. 1956).

11.13 Prevention and Management of Cancer Induce Nausea and Vomiting One of the furthermost disliked side effects of cancer therapy is nausea and vomiting. The patients get aversion for food and even at the sight of food. The patient feels nausea and may experience vomiting sensation. The management of this side effect can be done by evaluation of nausea and vomiting. Further evaluations include emetogenic potential and the pattern of the anticancer regimen to be administered. It is always wise to give antiemetics prophylactically. It is also very important to be aware that each patient has different threshold for nausea and vomiting. Pharmacist

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

205

should be able to suggest to the doctor a cost-effective therapy for antiemetic. Institution-specific guidelines regarding antiemetics if available shall facilitate the tracking of outcomes and deduction of cost (Ryan 2010).

11.14 Pain Management and Nutrition Cancer pain may be due to infection, tumor, and treatments. The types of pain in cancer are either nociceptive (pain signals from nerve endings) or neuropathic (damage to nerve fibers). The diagnosis involves elaborate patient’s history considering whether the pain is located at single or multiple sites. It is also very important to evaluate the effect of pain on patient’s life. One can use guidelines given in WHO pain ladder (Nersesyan and Slavin 2007).

11.15 Nutrition in Cancer Diet plays a significant part in the treatment and recovery of cancer. Recommended diet for cancer includes rich in fruits and vegetables. Whole grains, legumes, fish, and food low in fat lower the recurrence of colorectal cancer and breast cancer recurrence and mortality due to improved survival rates; thus, healthy diet has become important. Radiation therapies lead to oxidative stress in patients due to release of reactive oxygen productions. Antioxidants are invariably administered as supplements to counter oxidative stress. Antioxidants protect the normal cells from reactive oxygen species which caused damage to the healthy cells. Antioxidants improve tolerance of the patients to the treatment and higher dosage. Antioxidants also quenching the reactive oxygen species reduce harmful effects. It may facilitate the damage repair from treatment and inhibit apoptosis. The supplements in cancer treatment are indicated during and after treatment by multivitamins. It also indicated when the patient has been diagnosed as deficient in nutrition by laboratory investigations and due to health problems associated with cancer (Ravasco 2019).

11.16 Case Studies 11.16.1 Hepatitis C Case Study: Specialty Pharmacy Approach 11.16.1.1 Background Hepatitis C is a viral infection (causing virus is hepatitis C virus (HCV)) causing the inflammation of the liver. The person gets the infection by coming into contact with fluids and secretion of infected person with HCV. Hepatitis is treated by using antiviral drugs specially for HCV virus. Adherence to the therapy is very important in management of the disease. Pharmaceutics-based scientists are now coming with

206

A. N. Nagappa and J. Kanoujia

more oral formulations instead of infusion. Targeted therapies are causing less side effects with enhanced efficacy and able to reduce the duration of treatment. In May 2011, two drugs were approved and utilized in combination with pegylated interferon and ribavirin for the treatment of hepatitis C. This new regimen was able to reduce the duration of period from 48 weeks to 24–28 weeks for the patient with HCV genotype 1. Adherence to the therapy is necessary for positive outcome. These special medications also cause acute and chronic side effects; here, the role of specialty pharmacist comes into light for patient education and counseling before and during treatment.

11.16.1.2 Hepatitis C Case Study Specialty pharmacy can provide services like checks on drug-drug interactions, medication therapy management, refill reminder program, providing patients access to disease-specific financial assistance, and injection trainings for cost-saving outcomes for patients, pharmacy, and provider. Clinical pharmacist can increase the patient adherence to the therapy that may result in improved life of patient. In the next section, one case study is presented to investigate the impact of a specialty pharmacy refill reminder program on hepatitis C patient adherence and incidence of early virologic response. 11.16.1.3 Day 1: Receipt of Order—Patient Name, Mr. Ratan Sharma (RS); Date of Birth, October 19, 1954 Diagnosis: Hepatitis C HCV genotype: 1a HCV viral load is 5,123,345 IU/mL Rx

1. Ribavirin 600 mg PO BID 2. Pegylated interferon alpha-2a 180 mcg SQ QW 3. Telaprevir 750 mg PO every 7–9 h with food Abovementioned medicines are taken by patient, so drug-drug interaction needs to be verified. Clinical pharmacist has noticed that apart from these medicines, patient is also using medicines like lisinopril, amlodipine for St. John’s wort, aspirin, bupropion, and ibuprofen. The clinical pharmacist found two cases of drug-drug interactions, and then he/she calls the patient to discuss. The below-mentioned combination is the case of drug-drug interaction: 1. Telaprevir + amlodipine ¼ increases concentrations of amlodipine 2. Telaprevir + St. John’s wort ¼ decreases concentrations of telaprevir The clinical pharmacist provides information to Mr. RS regarding the safe use of new medications he will receive from the pharmacy. He/she also review the side effects he experiences, importance of adherence, what OTC or herbal product patient

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

207

is using, and what to do in case of missed dose. At last, he/she informs Mr. RS regarding next appointment after 3 weeks. Clinical pharmacist also sends the fax to a prescribing doctor regarding drug-drug interactions present within doctor’s medication regimen.

11.16.1.4 Day 4 Doctors have called the clinical pharmacist to appreciate him/her for alerting him about the drug-drug interaction. Pharmacist has also recommended to reduce the dose of amlodipine to 5 mg. 11.16.1.5 21 Days Later After 21-day treatment, pharmacy technician calls Mr. RS to schedule his medication refill. During the call, he/she also inquires Mr. RS about his well-being, his adherence to the therapy, and his laboratory visits. Mr. RS also informed the pharmacy technician about the appearance of rashes in his body and discomfort in anorectal area after starting his medication. 11.16.1.6 7 Days Later It has been about a month since Mr. RS started taking his medication. The clinical pharmacist calls him to check about any side effects that he was experiencing since starting the medication. Mr. RS states that he is doing well and that the side effects have subsided (Stephanie and Rosemary 2011). 11.16.1.7 Critical Commentary Treatments of hepatitis C are provided to patients in an ambulatory care as patient is able to self-care. The treatments are recommended for specialty care due to the complex nature of treatments and possible risk to the patient. This disease can spread to other healthy individuals who are in close proximity to the patient. The integrated teamwork and intellectual inputs are important apart from the drugs and devices. The patients and his caretaker have a major role as far as adherence to therapy is concerned. Apart from patient education, communication and teamwork of caregivers and care receiver are the cornerstone for the success of therapy.

11.17 Case Study 11.17.1 Adverse Drug Reactions to Ibuprofen: A Case Report Ibuprofen is a commonly used medicine (prescription as well as over the counter) for the treatment of headache, fever, joint pain, inflammatory states, and migraine-like issues. The combination of paracetamol is usually available with various drugs. Some of the side effects of ibuprofen are hepatic toxicity, rash, gastrointestinal ulcers, anaphylaxis, and hepatic toxicity. One study reported that ibuprofen induced severe distress hypersensitive reactions in patient. Ibuprofen also causes severe laryngeal edema and

208

A. N. Nagappa and J. Kanoujia

bronchospasm in the patient within 2 h of ibuprofen consumption. In that case, salbutamol, deriphyllin, supportive oxygen, and hydrocortisone are used for treatment, but the patient was not responding well and went into coma. There is no antidote for management of adverse drug reactions caused by ibuprofen, and now it becomes a big challenge for physician to manage the patient condition. As per the literature, histamine antagonist is the choice of medicine for the treatment of allergic or drug-induced laryngeal edema and bronchospasm. Epinephrine is very effective because of direct action on target organs. Adverse drug reactions that arise due to intake of ibuprofen can be prevented by educating patients/public/families regarding adverse drug reactions, avoiding unwarranted intake of ibuprofen, drug audit, record keeping, monitoring of drug reactions, and reporting off ADRs to the state or central pharmacovigilance agency (Khobragade and Khobragade 2016).

11.17.2 Critical Commentary Adverse drug reactions are unintended drug reactions which need to be watched and documented in order to count the potential threat to the patients who are using them for therapeutic purposes. Any drug can cause ADR, as it is the reaction of the individual to the drug. Even OTC drug like ibuprofen can cause ADR which can be fatal. It becomes important to develop a system of reporting, analyzing, and documenting all therapeutic agents. Although all drugs have undergone safety and efficacy tests as per the regulatory agencies, the clinical trial data cannot be relied upon by the whole population. Whenever and wherever, ADR happens to any person, and treatments should be given immediately as some reactions like anaphylactic shock can lead to severe morbidity and mortality.

11.17.3 Case 11.3 Pharmacovigilance In the present case study, the drug mefloquine (Lariam) used for malaria was found to cause neuropsychiatric side effects, which is rare. Two cases were reported in which the patient complained about mood disorder like major depressive episode with psychotic nature and mania. These patients were taking drug as malaria prophylaxis.

11.17.3.1 First Clinical Case A man aged 31 years used mefloquine 250 mg per week as prophylaxis medicine for malaria. After taking five doses (250 mg) of mefloquine, he developed psychotic symptoms like mania. He also experienced delusions and persecution with some auditory hallucinations. Blood report and physical examination come out normal. The patient was treated with neuroleptic drug (olanzapine 20 mg/d) for complete resolution of symptoms at the end of 3 weeks.

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

209

11.17.3.2 Second Clinical Case Similar case was observed in a 27-year-old man who complains about having psychotic symptoms and depressive episode after taking mefloquine in a dose of 250 mg per week as malaria prophylaxis. His laboratory report including blood test, MRN, and serology was normal. The psychotic symptoms were treated for 4 weeks with the use of olanzapine (20 mg/d) and clomipramine (150 mg/d). Mefloquine is known to be a safe and effective drug for chloroquine-resistant malaria. Minor neuropsychiatric side effects that occur with the drug include anorexia, dizziness, fatigue, ataxia, and sleep disturbance in approximately 40% of patients. Severe adverse reactions are rare, but in some patient, it may cause serious delusions, mood disorder, suicidal tendency, panic attacks, conversion, and manic excitation. A patient with a family history of psychiatric disorders is more prone to severe reactions. Alcohol consumption and intake of other drugs (like quinine) are two other risk factors. It is important for physician to be concerned about the severe neuropsychiatric side effects of mefloquine as malaria prophylaxis. It requires investigation of the risk factors such as personal or family history of psychiatric disorders (Oueriagli Nabih et al. 2011).

11.17.4 Critical Commentary Prophylaxis treatment will work if the person who is not suffering from malaria but planning to visits place where malaria is reported. It is quite likely that patients are on medication for other conditions for which they are prescribed medicine. Patients and health consumers need to be alerted in general about possible drug-drug interactions which may happen and cause discomfort to serious drug reactions. The pharmacovigilance has assumed paramount importance as it collects data from which we can calculate the potential hazard for public health on its long-term use which cannot be revealed by clinical trials. The pharmacovigilance analysis helps the regulatory agencies to continue or ban a particular drug from marketing. Recently, H2 blocker ranitidine was indicated as a risk for causing cancer. It was immediately banned and withdrawn from market based on pharmacovigilance evidence.

11.17.5 Case 11.4 Pediatrics: Pediatric Fever and Cough Baby Shreya Singh (SS, 5 years) presented with runny nose and a fever of 100.9
F. Her mother visited the pharmacy asking for drug she can use for the treatment of her daughter. The pharmacist inquired mother about her allergy to any drugs. The girl is taking gummy vitamin daily, and her weight is approximately 17.2 kg. SS’s mother has used acetaminophen and ibuprofen for treating cold-like symptoms in the past. SS’s mother wants to know which antipyretic is suitable for her daughter this time. The girl has low-grade fever, and she can take acetaminophen at a dose of 15 mg/kg. Her mother also instructed to follow the package directions. As per weight of the girl, she should receive acetaminophen at a dose of 250 mg with the interval of

210

A. N. Nagappa and J. Kanoujia

4–6 h. Counseling of mother is required not to exceed the 5 doses in 24 h and always prefer pediatric formulation for her girl. If the fever persists for more than 3 days, the girl should be taken to the doctor. The mother should also be informed about not to alternate the use of ibuprofen and acetaminophen products due to the risk of overdose.

11.17.5.1 Critical Commentary It is very important to remember that children are special populations and they have different requirement of doses as they vary physiologically from adults. Sometimes children may become seriously ill quickly and need hospitalization. Children are overlooked and treated with self-medication by parents which may be dangerous. Children unlike adults are in developing phase with weak organs needs to be looked upon with special care and concern. Especially in diarrhea they can become seriously sick leading to dehydrated state and become victim of hypovolemic shock. The dose requirement is different, and the pharmacist should be able to calculate the dose and provide suggestions and formulations required by the particular child. Children are not to be administered with aspirin and can be given paracetamol. Aspirin may cause gray baby syndrome, and paracetamol is safe in children as they have good liver capacity to metabolize drugs (https://www.pharmacytimes.com/publications/ issue/2010/november2010/otccasestudies-1110).

11.17.6 Case 11.5 Pharmacy Practice in Geriatrics Pratibha Verma (PV) is an 82-year-old elderly patient with a history of glaucoma congestive heart failure, osteoarthritis, and hypertension. Presently, she taking medicines like lisinopril, furosemide, metoprolol, potassium, timolol maleate ophthalmic solution, multivitamin aspirin, acetaminophen (if required), and a calcium/ vitamin D supplement (800 IU daily). Now, she visited new orthopedic physician and complains of long-lasting arthritic pain in her knee. The physician prescribes the meloxicam (NSAID, dose, 7.5 mg per day) for relieving pain and inflammation. As per orthopedic doctor, meloxicam is a good choice to help the patient relieve pain, but it can be a risky approach because of negative side effects on the heart. NSAIDs are also dangerous to patient like PV’s age, because it may cause serious thrombotic and cardiovascular event leading to stroke and myocardial infraction. Gastrointestinal-related side effects such as ulcer, intestinal perforation, and bleeding are also alarming side effects for elderly patients. Pratibha Verma is also in regular contact with their family doctor. She informed her family doctor about his new medicine recommended by an orthopedic doctor. He advises her not to take the medicine and go for pain management plan. Now as per new plan, her dose of acetaminophen increased to twice daily in the form of extended-release acetaminophen (650 mg) tablet. For long-lasting severe pain, tramadol 25 mg is prescribed to be taken every 4 h (as per requirement). Doctor also recommended 1% topical gel containing anti-inflammatory diclofenac sodium to reduce the side effect as compared to systemic administration. Inclusion of

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

211

physiotherapist is also a good option for strengthening as well as range-of-motion exercises.

11.17.6.1 Critical Commentary Geriatric patients as special population are frail by nature due to aging. They are usually suffering from multiple conditions and are on polypharmacy. They need to be seen by pharmacist to observe any deviations in health as by nature they cannot do any physical activity. They are vulnerable to conditions like dementia, lack of sleep, constipation, depression, cardiovascular conditions, and many more age-related diseases. They have fragile bones, leading often to bone fractures, and become bed-ridden. They have poor metabolizing capacity. They need to be cared as they can fall sick. They cannot tolerate paracetamol and can be given aspirin with caution (https://www.netce.com/casestudies.php?courseid¼1755).

11.17.7 Case 11.6 Women During Pregnancy A 28-year-old woman named Pramila Khanna (PK) has epilepsy issues which are well controlled by using valproic acid. Now, she is interested to get pregnant for the first time and seeks advice regarding epilepsy medicine management during her pregnancy. She is not having any allergy issues, has no other medical issues, does not take any other medicines/supplements, and does not smoke and drink. She is also interested to know whether using valproic acid is safe or not during pregnancy. Valproic acid is well known to cause birth defect especially neural tube defect if taken during the first trimester of pregnancy. That’s why, PK shifted to alternative antiepileptic medicine before getting pregnant. The management of epilepsy is important during pregnancy as it can be dangerous for both the mother and the baby. The best way is to select the antiepileptic drug with low profile of risk such as levetiracetam and lamotrigine and consult with neurologist. As per studies, carbamazepine may be a safe option as well (https://www.pharmacytimes.com/ publications/issue/2013/december2013/case-studies-1213). Pharmacist must play an important role in this case while shifting of drug from valproic acid to other less risky drugs. Close monitoring of PK is very much required during transition stage, and folic acid (vitamin B9) supplement should be stated to lower the baby’s risk of birth defects.

11.17.7.1 Critical Commentary During pregnancy, women are to be careful as the medicines they take are likely to affect the neonate which is growing in their womb. General principles of drug therapy during pregnancy and lactation are using medication only if absolutely indicated, avoiding initiating therapy during the first trimester, selecting a medication with a proven track record in human pregnancy, using a single agent to avoid polypharmacy, using the lowest effective dose, and discouraging the use of over-thecounter drugs that might interact with prescription medications.

212

A. N. Nagappa and J. Kanoujia

11.17.8 Case 11.7 Cancer The role of pharmacists in improving patient treatment outcome in the clinical setting involves various practices in different areas. Oncology pharmacists are also recognized as oncology pharmacy specialists (OPSs) with specialized knowledge (Table 11.11) of anticancer medications. As vital fellow of the interdisciplinary team, OPSs help to minimize toxicities, optimize the benefits of drug therapy, and work on supportive care issues. OPSs expanded its role as experts in drug therapy to seven major key elements of medication management that include selection, procurement, storage, preparation/dispensing, prescribing/dosing/transcribing, administration, and monitoring/evaluation/education (https://www.dovepress.com/ role-of-pharmacists-in-optimizing-the-use-of-anticancer-drugs-in-the-c-peerreviewed-fulltext-article-IPRP#).

11.17.8.1 Critical Commentary Pharmacists have acquired the status of oncology pharmacy practitioners by closely working with cancer patients, nurses, and doctors. Anticancer drugs are highly toxic. Table 11.11 Oncology pharmacist practice and drug-specific interventions S. no. 1 2 3 4 5 6 7 8 9 S. no. 1 2 3 4 5 6 7 8 9 10 11 12 13

Oncology pharmacist practice for supportive care Palliative care and parenteral nutrition support Pain management, side effect management Infectious disease and antibiotic support—immunization Chemotherapy administration follow-up Hematology support—anemia, anticoagulation clinic Gastrointestinal side effect support Chemoprotective agents—protocol development, dosing Cutaneous/dermatological support—skin rashes Chronic disease medication management—asthma, hypertension, diabetes, hyperlipidemia, cholesterol management Oncology pharmacist drug-specific interventions Adverse drug reaction prevention and monitoring Patient education Medication administration support, premedication, hydration Therapeutic drug monitoring Addition of necessary medications Writing prescriptions and refills Discontinuation of drugs Assuring medication adherence Dose adjustments for organ dysfunction, weight, age Laboratory monitoring Pharmacokinetic monitoring Medication reconciliation and allergies Switch intravenous to oral formulations

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

213

Oncology pharmacy practitioners run a very high risk of cancer due to occupational hazard.

11.17.9 Case 11.8 Pain Management Avni Gupta (AG) is a woman (aged 18 years) who speaks to the pharmacist at her college’s student health center for a medication to improve cramps. She also complains about the abdominal pain, headache, fatigue, and nausea the previous day. Upon questioning, the pharmacist comes to know that she is presently menstruating, is not sexually active, has no chronic medical issues, and is not allergic to any medicines. She also states that recently she started smoking cigarettes and she used to take ibuprofen for the same symptoms in the past, but her stomach got upset, and the pain is still not relieved. The pharmacist has counsel her about the safe use of ibuprofen and other safe alternatives she could use for symptoms. AG also informed the pharmacist about the primary dysmenorrhea which can cause release of prostaglandins, inflammatory mediators, and leukotrienes with uterine vasoconstriction, pain, and ischemia during menstruation. Due to prostaglandin release, she experiences diarrhea, nausea and vomiting, and headache. OTC-NSAIDS are the most commonly used for menstrual pain management. Ibuprofen is the best drug for the menstrual pain management, but it also causes gastrointestinal side effects. The pharmacist recommended her to continue the use of ibuprofen (dose of 200–400 mg) every 4–6 h as per requirement (maximum dose up to 1200 mg/ day). To resolve GI upset issue, she should take medicines with food. The pharmacist also advises AG to take medication as per scheduled at least for the first 24–48 h of menstruation rather than as needed basis (levels of inflammatory mediators are the highest in starting of menstruation). Application of heat pads and smoking cessation may help her to improve the symptoms.

11.17.9.1 Critical Commentary Pain is a very unpleasant thing to experience. Everyone tries to avoid or lessen the intensity. In women, during menstrual periods, very powerful contraction leads to intensive pain. Usually, people rely on ibuprofen and paracetamol. In musculoskeletal pain using faced by osteoarthritis patient, one need to use NSAIDS may cause GIT disorder and hyperacidity in another patient.

11.17.10 Case 11.9 Nutrition Nutrition is an area where pharmacists must play an important role to aware the public, for example, appropriate use of salt and sugar. Otherwise, it would be the reason for hypertension and diabetes. One need continuous education programs of nutrition not only to update but also to motivate patients regarding diet and lifestyle modifications.

214

A. N. Nagappa and J. Kanoujia

Ms. Savita is a 43-year-old woman, living in Residential Habilitation Center. Now, the pharmacist noticed that she had begun to lose weight. The pharmacist had advised her to eat more nutritious food on schedule; despite this advice, she was still losing weight about 8 kg. During counseling, it was found that Ms. Savita was generally taking breakfast and skipping lunch and dinner by dumping the food in the garbage. She was also not drinking enough water, and the pharmacist was not able to determine the reason behind this. After that, the pharmacist decided to use the “Determine Your Nutritional Health Checklist” to see if she was at nutritional risk and found that she was at high nutritional risk with a total score of 11. The pharmacist has counseled her to follow proper diet plan with good amount of protein, carbohydrate, antioxidants, etc.

11.18 Conclusion Pharmacy practice is under different stages of development like well-established in developed countries and underdevelopment in developing countries. The evidencebased medicine, soap analysis, pharmacoeconomics, and pharmacogenomics are under consideration, whereas pharmacovigilance is making a big way. Careful consideration of the effect of drugs on individual patient and application of the knowledge of medicine including optimization of patient’s conditions for the benefit of the patient are challenging activities.

References Albassam A, Awad A (2018) Community pharmacists' services for women during pregnancy and breast feeding in Kuwait: a cross-sectional study. BMJ Open 8(1):e018980. https://doi.org/10. 1136/bmjopen-2017-018980 Buck ML, Connor JJ, Snipes CJ, Hopper JE (1993) Comprehensive pharmaceutical services for pediatric patients. Am J Hosp Pharm 50(1):78–84 Coulter DM (2000) The New Zealand intensive medicines monitoring programme in proactive safety surveillance. Pharmacoepidemiol Drug Saf 9:273–280 Cruz EP, McDonald GO, Cole WH (1956) Prophylactic treatment of cancer; the use of chemotherapeutic agents to prevent tumor metastasis. Surgery 40(2):291–296 Hu Q, Hu H, Hu M, Yang Y, Wu Z, Zhou N (2020) Patient preferences for specialty pharmacy services: a stated preference discrete-choice experiment in China. Front Public Health 8:597389. https://doi.org/10.3389/fpubh.2020.597389 Jaehde U, Liekweg A, Simons S, Westfeld M (2008) Minimising treatment-associated risks in systemic cancer therapy. Pharm World Sci 30(2):161–168. https://doi.org/10.1007/s11096-0079157-4 Jeetu G, Anusha G (2010) Pharmacovigilance: a worldwide master key for drug safety monitoring. J Young Pharmacist 2(3):315–320. https://doi.org/10.4103/0975-1483.66802 Kalaiselvan V, Kumar P, Mishra P, Singh GN (2015) System of adverse drug reactions reporting: what, where, how, and whom to report? Indian J Crit Care Med 19(9):564–566. https://doi.org/ 10.4103/0972-5229.164819 Kalaiselvan V, Mishra P, Singh GN (2014) Helpline facility to assist reporting of adverse drug reactions in India. WHO South East Asia J Public Health 3:194

11

Specialty Pharmacy Services: ADR Reporting and Pharmacovigilance,. . .

215

Keys PA, O'Neil C, Maher R (2004) Geriatric concentration: a new elective sequence in an entrylevel doctor of pharmacy program. Am J Pharm Educ 69(1):Article 7 Khobragade Y, Khobragade S (2016) Adverse drug reactions to ibuprofen—a case report. Int J Basic Clin Pharmacol 5:215–219 Lyszkiewicz DA, Gerichhausen S, Björnsdóttir I et al (2001) Evidence based information on drug use during pregnancy: a survey of community pharmacists in three countries. Pharm World Sci 23:76–81. https://doi.org/10.1023/A:1011227718654 Mărginean CO, Meliţ LE, Chinceşan M, Mureşan S, Georgescu AM, Suciu N, Pop A, Azamfirei L (2017) Communication skills in pediatrics - the relationship between pediatrician and child. Medicine 96(43):e8399. https://doi.org/10.1097/MD.0000000000008399 Nersesyan H, Slavin KV (2007) Current approach to cancer pain management: availability and implications of different treatment options. Ther Clin Risk Manag 3(3):381–400 Odegard PS, Breslow RM, Koronkowski MJ et al (2007) Geriatric pharmacy education: a strategic plan for the future. Am J Pharm Educ 71(3):47 Oueriagli Nabih F, Touhami M, Laffinti A, Abilkacem L (2011) Mood disorder after malaria prophylaxis with mefloquine. Encéphale 37(5):393–396 Pediatric Pharmacy Practice Guidelines (1991) Pediatric pharmacy administrative group committee on pediatric pharmacy practice. Am J Hosp Pharm 48(11):2475–2477 Ravasco P (2019) Nutrition in cancer patients. J Clin Med 8(8):1211. https://doi.org/10.3390/ jcm8081211 Rishi RK, Patel RK, Bhandari A (2012) Opinion of physicians towards adverse drug reaction reporting results of pilot study. J Commun Med Health 1:25–29 Ryan JL (2010) Treatment of chemotherapy-induced nausea in cancer patients. European Oncol 6(2):14–16. https://doi.org/10.17925/eoh.2010.06.02.14 Schrempp S, Ryan-Haddad A, Galt KA (2001) Pharmacist counseling of pregnant or lactating women. J Am Pharm Assoc 41:887–890. https://doi.org/10.1016/S1086-5802(16)31330-4 Schwartz RN, Eng KJ, Frieze DA et al (2010) NCCN task force report: specialty pharmacy. J Natl Compr Canc Netw 8:1–12 Shaller D (2004) Implementing and using quality measures for children's health care: perspectives on the state of the practice. Pediatrics 113(1 Pt 2):217–227 Sharma R, Kellarai A (2014) Pharmacovigilance and adverse drug reaction reporting perspectives among interns and postgraduates of a teaching hospital. J Pharmacol Pharmacother 5(4): 248–250. https://doi.org/10.4103/0976-500X.142436 Shay B, Louden L, Kirschenbaum B (2015) Specialty pharmacy services: preparing for a new era in health-system pharmacy. Hosp Pharm 50(9):834–839. https://doi.org/10.1310/hpj5009-834 Shin H, White-Traut R (2005) Nurse-child interaction on an inpatient paediatric unit. J Adv Nurs 52(1):56–62. https://doi.org/10.1111/j.1365-2648.2005.03564.x Sleath B, Svarstad B, Roter D (1997) Physician motivation for non-scientific drug prescribing. Soc Sci Med 44:541–548 Stephanie SH, Rosemary K (2011) Specialty pharmacy times, Hepatitis C case study at prosperity specialty. Pharmacy 24:34 Talbot JC, Nilsson BS (1998) Pharmacovigilance in the pharmaceutical industry. Br J Clin Pharmacol 45:427–431 WHO (2002) The importance of pharmacovigilance safety monitoring of medicinal products. WHO Lib Catalog Woelfel JA, Boyce E, Patel RA (2011) Geriatric care as an introductory pharmacy practice experience. Am J Pharm Educ 75(6):115. https://doi.org/10.5688/ajpe756115

Medication Therapy Management: Importance and Practice

12

A. N. Nagappa and Jovita Kanoujia

Abstract

Medication therapy management is a practical approach toward achieving best patient safety and outcomes by application of existing knowledge about prescribed medications. It is also input from the patient which are also to be considered. The therapeutic outcomes are the benefits for the patient. Application of software has revolutionized the MTM practice. Although the MTM has been criticized for raising the expense and duration of therapy, the benefits it provides are undeniable. Keywords

Personalized therapy · MirixaPro · Risk-benefit analysis · Personal medication record

12.1

Introduction

Markets are loaded with a large number of products which are manufactured with a hope of successful sale leading to a profit. There is nothing wrong if the pharmaceutical products are promoting health of an individual without causing any harm to the person who is prescribed and recommended to use it under exclusive disease conditions. For example, a cough remedy is useful only when someone has uncontrollable cough, similar in the case of pain killers. It is a well-established fact that all therapeutic medicines need to be assessed for safety by rough estimation of riskbenefit analysis and then prescribed to a patient if benefits overweigh the risks. Pharmaceutical industry is pushing the products in the market with heavy discounts A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_12

217

218

A. N. Nagappa and J. Kanoujia

and incentives to the prescriber, so that they empty all the stock in quarantine. In this endeavor, the ethics and corporate objective of industry are mocked. Instead of providing relief to the patients, there are many instances of serious drug-induced injuries causing serious organ damage and death to the patients (Ferreri et al. 2020). There are regulations enforced to curb such practice. Due to the lack of serious commitment by regulators and law enforcement agencies, exploitations of the health consumers and patients are going on unabated. Patients having chronic diseases need to be monitored continuously for the outcome of therapy, so that one gets information, whether the given treatments are working or not. However, do patients and health consumers who have loyalty and faith on the caregiver ever think of outcomes from the therapy? If the caregiver says anything, patient accepts without a thought. The caregivers are overburdened by a large number of patients; in this pretext, they take excuse over the lapses of treatments and even exploit emotionally the patients and the health consumers, making him solely responsible for any deviation or upset in health. Several times the patient tries to avoid the healthcare provider as he is very much scared to face the prescriber. The doctors are not questioned and are not documenting the treatments provided. The patient condition continuously worsens, asymptomatically leading to sudden causalities such as heart attacks and stroke. However, the patient would have been in touch of a doctor, paid consultation charges, and followed all the instructions and taken all the medicines prescribed by the doctors. This condition does not prevail in developed countries, where the provider is asked to document every treatment given to his patient and be ready to defend his treatments with rationality, in case anything goes wrong, and the patient approaches the court of law for justice. It is although professional services, the patient has every right to know regarding the qualifications of healthcare providers, why they chose to prescribe a particular medicine. The governments and regulators have become aware of the issue and are becoming vigilant by implementing and enforcing suitable laws and regulations to shift from product-centric to patient-centric. For example, the industry is asked to print the generic name of the medicines in bold fonts, so that all the stakeholders come to know the medicine and if there are any alternates available which may be inexpensive than the prescribed brand. The doctors are being continuously reminded to write prescriptions with generic names rather than brand names. Recently, the retail pharmacy and chain pharmacies are asked to stock and store the Jan Aushadhi medicines (generic medicine) in separate cupboards and sell them to patients who ask for generic medicines (Smith et al. 2017). The councils of healthcare providers like Pharmacy Council of India (PCI), Medical Council of India (MCI), and Indian Nursing Council (INC) are asked to continuously monitor their members for ethical practices of profession. It is very evident that doctors are having unholy liaison with pharmaceutical marketing team and retail pharmacy and are indulging in selling of prescription medicines without prescription which blatantly violate the law. The MCI has warned all the registered medical practitioners in public that the Council will not spare anyone having business relationship with pharmaceutical industry. The consequences of such liaison are likely to influence the choice of medicine in a disease for a patient. It

12

Medication Therapy Management: Importance and Practice

219

shall turn up the doctors as advocates of brands instead of caregiver. On the other hand, retail pharmacy outlets are becoming more of sales points instead of dispensing practice. It is very much pathetic to say that in a retail pharmacy the registered pharmacist would have rented her/his certificate to the shop owner who does not have any pharmacy education or background. These instances of mockery of law lead to many unnoticed drug injuries, and at large, the patients in India are deprived of good outcomes of modern medicine. If any good things are to be said, it is about nurses who have been serving the patients, without serious violation of ethics and rules (Bouvy et al. 2015). The Indian Government has brought out several rules, regulations, and reforms to modernize the healthcare system, thus leading to the introduction of 6-year Pharm D Regulation in 2008 and enactment of pharmacy bridge course (BS Pharmacy Practice for 2 years) to update the knowledge, skills, and qualifications of diploma of registered pharmacist in pharmacy. Introduction of pharmacy practice guidelines 2015 empowers the registered pharmacist to practice pharmacy. It is also observed that many patients across the country suffering from chronic conditions are having the problem of resources to manage their healthcare expenses. The Jan Aushadhi outlets make the provision of affordable medicines to the needy patients. Public awareness has improved education on the adverse drug reactions (ADR) induced by therapeutic prescription drugs, and the casual attitude is being phased out. Mass media like television, radio, and print along with social media continue to report on the ADR of drugs. Due to the activism of the public and looking at the practice of healthcare in developed countries, Indian healthcare system is keen to update the pharmaceutical regulations. The latest development in the practice of pharmacovigilance (PV) is game-changing influencing the healthcare practice. It is mandatory for a manufacturer to collect primary data of pharmacovigilance and submit to the Pharmacovigilance Programme of India (PvPI) Center. Due to wellorganized protocol and application software, all the manufacturing company must collect the pharmacovigilance data. After this mandatory rule of submission, all companies began pharmacovigilance practice with the aim to identify drugs which are causing serious ADR and review its potential to cause harm to the patients. It is important to submit PV data for continuing of license for marketing. The PV data obtained is also discussed in the Drug Technical Advisory Board (DTAB) meetings. The pharmacovigilance data is utilized in deciding whether the given drug in question has adequate safety and is the benefits derived by using drug overweigh the risk to the patients while using the drugs. So, pharmacovigilance practice is a step toward patient-centric care (Ventola 2018). It is quite astonishing to see we have nearly one lakh brands of medicine in the markets. There is only name in the brand without the brand value. The names of these brands are highly illogical and suffer from the fact that they are look-alike and sound-alike issue. The price of these branded medicines is usually very expensive, resulting in poor patient compliance. In order to control this menace, the Government of India has made several regulations and drug price control orders along with amendments to ensure that medicines become affordable to the patients. In 2008, Jan Aushadhi Act was enacted, and now, the Government of India is opening Jan

220

A. N. Nagappa and J. Kanoujia

Aushadhi Kendra, which dispenses medicines for chronic conditions like blood pressure, diabetes, etc. These medicines are quality assured by the government and are 50% cheaper when compared to the brand medicines prescribed (Deshpande Prasanna et al. 2018). All the above changes are happening across the globe and India is no exception. The overimportance on product and competition within has misled the pharmaceutical industry to forget its corporate responsibility. Influencing the prescribers to prefer particular brand and prescribe more has caused much damage to healthcare delivery and eroded the ethics of medical practice. The government should discourage pharmaceutical industry from unethical marketing by mass media reporting and public response. We are seeing a change in the pharmaceutical industry that is making attempts to become wellness industry. The pharmaceutical industry is keen in changing over therapeutics segments to nutraceuticals, and wellness products are a strong evidence of paradigm change from product to patient. The nutraceuticals industry in India is rapidly growing at 20% in Asia-Pacific region and currently is worth about $2.2 billion and is predictable to grow at 20% to $ 6.1 billion by 2019–2020. The major drivers of these growths are attributed to consumers’ increased interest in health and nutrition. In the last 10 years, there has been a drastic change found in lifestyles of Indians. Involvement of packaged and fast foods in diet with sedentary lifestyle has resulted in an upsurge in lifestyle-related disorders such as obesity, diabetes, and cardiovascular disease. This fosters the higher usage of nutraceuticals over the prescription drugs by Indian consumers (upper middle class and higher socioeconomic). These nutraceuticals are also considered to prevent diseases and boost energy and mental alertness apart from providing daily nutritional requirements. The dietary supplement market in India holds the major share including more than 500 brands. Market of vitamins and minerals is a very competitive market and open for the foreign player. Research and development in the field of nutraceuticals will increase in the near future (Sharma and Majumdar 2009). The Central Government is enacting measures such as requiring doctors to issue prescriptions for generic medicines and manufacturers to publish the generic name in big letters in a bold typeface on drug labels; and enforcing the terms of the Pharmacy Act 1948 and the D&C Act 1940 in their entirety. Implementations are going to change the scenario from product-centric to patient-centric. The fundamental elements of medication therapy management are doctors, pharmacists, nurses, and other healthcare professionals. One of the stumbling blocks in seamless healthcare provision is the lack of communication either among healthcare professionals or with patients. The patient under duress is unable to stand up and ask the healthcare professional the vital information from them. The responsibility of providing the information is on the healthcare provider. The pharmacist is having more friendly relationship with the patients. Patients trust the pharmacist especially community pharmacist as they are easily accessible to the patient. They don’t need to have an appointment for discussion with a pharmacist about their health issues. They usually don’t charge any hefty consultation fee, and their service fee is usually covered by insurance provider or by the

12

Medication Therapy Management: Importance and Practice

221

government. However, their services are limited as they cannot give an extensive treatment like in clinics and nursing homes. They are popular among health consumers for treatments of minor ailments and recommending the patients to avail higher level of care, if they suspect a major disease. Pharmacists have remained in a unique position connecting between higher level of care and nonserious conditions (Hohmeier et al. 2019). The complexity of treatments has increased in recent times due to multiple diseases and polypharmacy. There is a need to evaluate for drug interactions with other drugs and food. These exclusive precautions are very important not only to achieve the outcomes of therapy but also to protect the patients from ADR and side effects and ensure patient safety. In the changed world of patient-centric therapy, one should think how to improve the clinical outcome at the minimum cost of treatments. These ideas have made the healthcare provision being integrated services. The key issue is to enhance communication among healthcare provider and patients. Medication therapy management (MTM) is intended to be a patient-centric service. MTM is optimization of outcomes by measuring the medications used and adherence of medications. MTM also attempts to address potential gap in therapy, identify barriers to optimal outcomes, and accept effecting therapy. MTM program should ensure optimum therapeutic outcomes for targeted beneficiary through improved medication use. MTM minimizes the risk for adverse drug reaction. The basic structure of MTM consists of a licensed and practicing pharmacist and doctor who should have agreed to cooperate among themselves in the interest of the patients’ outcomes (Sharma and Majumdar 2009; Herbert et al. 2006). The benefit for pharmacy from MTM is an increased number of prescription fill along with improved adherence. It is observed that improving the adherence has a direct impact on prescription fills which enhances the sale of prescription medicine. The primary activity of MTM is to identify the gaps in the therapy and give care. The MTM aims to fill those gaps which may reflect in addition of new drugs which again in turn result in new prescription with additional revenue for the pharmacy. MTM takes the stock of patient’s drug diseases and lifestyles. The pharmacist will be able to identify the need for vaccination to prevent patients from getting diseases. In the event of a lack of protection, the pharmacist should consult and advocate for the patient regarding the necessity for immunization. In this manner, the pharmacist who is licensed to provide immunization gets benefitted by service fee and margin of sale by vaccine. When pharmacists engage with the community and meet their healthcare needs, they become closer to the community. It is not a strange thing that a trust of bond develops between the pharmacist and patients. Patient begins to seek more and more advice from the pharmacist for minor ailments and also clarifies doubt about prescribed medicines. Patients are learning and getting convinced about how to use medicines. In this course of events, patients start developing dependence and trust on the pharmacist. Further, the patients seek advice regarding OTC medicines to resolve issues like fever, cough, cold, constipation, diarrhea, allergic rhinitis, and minor illness. Pharmacist and pharmacy get benefitted due to very personal relationships and result in sale of medicines and cosmetics through their recommendations which is known as counter sales. In counter sales, a pharmacist uses his expertise and tries

222

A. N. Nagappa and J. Kanoujia

to help patients by suggesting the appropriate healthcare tips. This creates another opportunity and market for the pharmacy. Implementation of MTM program in the pharmacy improves the image of the pharmacy. MTMs are often part of a range of paid services reimbursed by the public health department, insurance company, or government. As a result, MTM creates a win-win situation for patients, pharmacists, doctors, and third-party reimbursement agencies (health insurers, nonpublic health companies, co-ops, government subsidy payments, etc.). In MTM, patients have to register in a pharmacy which assures loyalty of the patients to a particular pharmacy. Existing patients recommend other patients regarding the quality of service and benefits they are getting from MTM program. This type of recommendation of new patients through word-of-mouth marketing is very much observed in the community pharmacies. Patients also feel secure and become responsible as they are also being treated as a part of decisionmaking regarding the treatment. For the implementation of MTM programs and collaborative practice agreements, the initiative is usually from the pharmacy and seldom from doctors. This is so because the pharmacist is the major beneficiary apart from patients among the stakeholders. Healthcare professional like doctors or nurse participating in MTM are indirectly benefitted. For example, doctor may not bother regarding medication part as this responsibility is managed by pharmacist. Assistances by the pharmacist will allow the physician to provide more time to patients with effective diagnosis and quality care (Stafford et al. 2017; Lounsbery et al. 2003). In MTM, it is important to audit the individual patients and make a study with referrals for following criteria. It should be started with following stepwise. Identification of drug therapy problems in the therapy is as follows: • • • • • • •

Taking/receiving the incorrect drug Taking/receiving of very less amount of correct drug Experiencing any adverse drug reaction Experiencing a drug-drug or drug-food interactions Taking/receiving of too much high dose of the correct drug Not taking/receiving the prescribed drug Taking/receiving a drug for no valid indication

Pharmaceutical industries which are developing new products are interested in evaluation of off-label use of medicine with bioavailability and bioequivalence (BABE) studies. Pharmaceutical industry may join the MTM center for collaborative research, as MTM have skilled professionals to conduct clinical experiment. Hence, this is an added advantage for developing MTM activities in community pharmacy. MTM practice improves adherence of medication which result in increased number of prescription refills. The MTM Center is highly rated in consumer perception of health and fitness for vaccination or ease of acceptance. Health consumers prefer MTM center over clinics; in clinics, health consumer should take an appointment and wait for call to get immunization, whereas in the MTM center, this may not be a scenario. MTM center may also offer services such as diet management and smoking cessations which can improve the cash pay to the pharmacy. There can be other

12

Medication Therapy Management: Importance and Practice

223

services like appointment-based screening/point-of-care services like bone density screening, blood pressure screening, and lipid profile measurement facilities (Powers and Bright 2008).

12.2

Assessing the Responses to the Treatments

MirixaPro resources are e-platforms which are commercially available for installation in MTM centers. These platforms have inbuilt software which can assess the MTM process. The software is aimed to provide output for patients with multiple diseases with multiple drugs. MirixaPro provides medication therapy management for conditions like asthma, chronic obstructive pulmonary disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, and osteoporosis. Furthermore, MirixaPro has built-in features to identify high-risk medications and drug interactions. The MirixaPro may also resolve diabetes medication with dosing chart elements and help with adult immunizations scheduled. MTM is a separate service or a combination of services offered by healthcare professional including pharmacist to provide patient-centric care and the best therapeutic outcomes for patient (Fig. 12.1). MTM has five core foundations like personal medication record, intervention or referral, medication therapy review, medication-related action plan, documentation, and follow-ups. MTM for cardiovascular disease prevention includes a broad range of services which aim at identifying uncontrolled hypertension, education of the patient on cardiovascular diseases, and medication therapies with finally advising patients on health behaviors and lifestyle modification for improved health. MTM is found to be highly effective for patients with multiple chronic diseases. For patients with multiple prescribers and high-cost medicines, MTM can be accomplished with or without collaborative practice agreements (Begley et al. 2011; American

Fig. 12.1 Summary of MTM learning by MirixaPro

224

A. N. Nagappa and J. Kanoujia

Pharmacists Association and National Association of Chain Drug Stores Foundation 2008).

12.3

History of Medication Therapy Management

From the beginning, pharmacy profession has been trying to implement pharmaceutical care and faced challenges in penetration from consumers and employers and struggled to understand exactly its identity and true value. Pharmacists faced a lot of barriers in providing pharmaceutical services, which include facility-related barriers such as lack of privacy and store layout as well as lack of space. Lack of personnel and lack of time with excessive workload have also been commonly cited as barriers to the provision of intellectual services. Furthermore, lack of financial support and legal liability are known to inhibit the provision of such services (Ramalho de Oliveira et al. 2010). Medicare Modernization Act of 2003 (MMA) was introduced in the United States, with the help of which pharmacy profession came up with the term “DTM.” Drug therapy management (DTM) is the facility of pharmaceutical care-based services to various groups of patients, which was practiced by pharmacists since many years. As per the Center for Medicare & Medicaid Services (CMS), each Medicare should establish DTM programs (DTMPs) for suitable beneficiaries as part of their benefits. DTMPs were designed to “optimize therapeutic outcomes via improved medication use” and “reduce the risk of adverse events, including adverse drug reactions.” Drug therapy management (DTM) is well-defined service(s) that optimize therapeutic outcomes for individual patients. One of the major goals of DTM is to reduce overall health costs besides improving therapeutic outcomes for patients. Other goals of DTM include enhancing patient adherence through education, detecting and resolving adverse drug reactions, and optimizing the effectiveness of medication regimens. India has genetically diversified population. Pharmacists were the only healthcare provider exactly cited as possible DTM providers (Pellegrino et al. 2009).

12.4

Advantages of Drug Therapy Management

In recognition of DTM, the federal government as per the MMA Act of 2003 provides pharmacists with the chance to expand and to be reimbursed for direct patient care services offered. Programs of this kind represent the pharmacy profession’s shift from a product-focused to patient-centered practice. The prescription medications can be made effective by prescribing the right medication at the correct dose and for the proper duration, providing medication accessibility to the patient. It ensures the patient’s medication adherence, monitoring whether the drug therapy objectives are being met, by minimizing adverse events and by providing patient education regarding their medications for effective management of their condition, especially for high-risk patients on chronic medical conditions and/or

12

Medication Therapy Management: Importance and Practice

225

elderly patients on complex medication regimens. The effective implementation of DTM services offered by DTMPs can result in enhanced patient care, results in improvement of overall health, and is also helpful in reducing overall cost of healthcare system. It can be possible by preventing adverse drug events, reducing improper medication use. The safe, appropriate, effective, and cost-effective use of medications is the predominant goal of DTMPs.

12.5

Role of PharmD in the Drug Therapy Management

Doctor of Pharmacy (PharmD) program is a new concept introduced for pharmacy students in the arena of pharmacy practice, which focuses on more patient-centered care. The American Association of Colleges of Pharmacy (AACP) designed PharmD curriculum to transform the role of pharmacist in providing the maximum healthcare services. Training pharmacist in patient care along and provisions of rational use of drugs is challenging task for mentors of pharmacist. As per the AACP, the clinical component is the most important area of instruction of the PharmD curriculum. The clinical component involves effective communication of pharmacist with patients and with practitioners or other health professionals. This is essential to do, the patient counseling, which is at the heart of the pharmacy renaissance. Pharmacists with a PharmD degree are well-equipped to provide these services (Mendonça et al. 2016). The purpose of the basic structure of DTM service delivery in clinical practice is to facilitate teamwork among the pharmacists, patients, physicians, and other healthcare professionals, to promote safe and effective use of drugs, and to achieve optimal patient outcomes. DTM services should support the establishment and maintenance of the patient and pharmacist relationship. The framework of DTM is presented in Fig. 12.2.

12.6

Essential Elements of an MTM Services

There are five essential elements for the delivery of medication therapy management (MTM). Each element given below integrates the services toward patient safety and efficacy of the treatments. Depending on the situations and patient conditions, one can decide the order of elements in MTM services: 1. 2. 3. 4. 5.

Medication therapy review (MTR) Personal medication record (PMR) Medication action plan (MAP) Intervention and/or referral Documentation and follow-up

226

A. N. Nagappa and J. Kanoujia

Fig. 12.2 The framework of drug therapy management

12.6.1 Medication Therapy Review Medication therapy review (MTR) is a systematic practice of collecting patient details, evaluating medication-related problems, developing a ranked list of medication-related complications, and designing a plan to resolve them. This review is conducted between the patient and pharmacist, where a pharmacist after having discussions with physicians, nurses, and patients tries to figure out gaps in the knowledge of patient regarding disease, drugs prescribed, doses to be taken, side effects of drugs, and other conditions (comorbidities and drugs used for those comorbidities). The problem of polypharmacy offers challenging situation, where pharmacist puts his intellectual inputs and optimizes the doses and order of administration of drugs. The pharmacist aims at achievement of minimum harm to the patients and good quality of life. Medication review involves the elaborate study of the patient clinical situation. The pharmacist shall be in continuous dialogue with the patient. He/she is updating the patient knowledge regarding drug, disease, and lifestyles which are important for dispelling the fear from the patients’ mind and making patient feel positive and confident about his condition. The patient empowered with correct knowledge likely to become responsible about his/her conditions and participate with his/her treatments enthusiastically. It would resolve the problem of patient noncompliance.

12

Medication Therapy Management: Importance and Practice

227

The drug therapy review (DTR) also deals with the collecting of patient-specific information to evaluate medication therapies and identifying drug-related problems (DRPs). Developing a ranked list of medication-related problems and planning to resolve them are also the major components of DTR. The patient or caregiver and the clinical pharmacist are involved in DTR and are conducted preferably in person and on the one-to-one basis. The one-to-one interaction enhances the clinical pharmacist-patient relationship. This results in early detection of DRPs and thus can minimize emergency situations, hospitalizations, and medication misuse. Patient education on the appropriate use of medications and monitoring devices and explaining the importance of medication adherence help them to understand treatment goals. The patient must receive personal prescription record at the end of a complete DTR, which contains detailed information about him or her. Drug therapy management also involves drug therapy review documentation, follow-up intervention and/or referral, medication action plan, and personal prescription record (Huiskes et al. 2017).

12.6.2 Personal Medication Record (PMR) The personal medication/prescription record (PMR/PPR) is generated with a purpose to help patients in self-medication management. The combined efforts of physician, patient, and pharmacist result in the maintenance of the PPR. Patients should be persuaded to maintain and update this document continuously. Patients should be recommended to keep the PPR with them and share it during the healthcare visits (Zeng et al. 2008).

12.6.3 Medication Action Plan The medication action plan (MAP) is a document comprising all the important instructions to be followed by the patients to track self-management. It helps the patient to understand which health concerns they need to address for associated actions that have been taken. The MAP is prepared by the combination work of patient and clinical pharmacist or other healthcare providers. The MAP can be generated at the time of patient discharge in institutional settings (Botermann et al. 2016).

12.6.4 Intervention and/or Referral Consultancy and intervention of clinical pharmacist are required to address drugrelated problems (DRPs). It may include to address problems with specific drugs while working closely with patients. The pharmacist should consult the healthcare providers to monitor or resolve existing or potential DRPs. Interventions should be made in this manner, so it fulfills the requirement of patients to optimize outcomes.

228

A. N. Nagappa and J. Kanoujia

Goals of therapy should be established in association with the patient or caregiver. It is not a compulsion to solve DRPs in a single visit. Clinical pharmacists should focus on goals and plan follow-up treatment as and when required. They may refer the patient to other healthcare providers as well as another specialized clinical pharmacist.

12.6.5 Documentation and Follow-Up Documentation is the essential aspect of the DTM service model. The pharmacist is responsible to generate, maintain, and update the documents related to the services and intervention(s) accomplished for evaluating treatment progress as well as billing purposes. DTM documentation mainly involves in making and maintaining an ongoing patient-specific record such as a record of all provided care in an established standard healthcare professional format (SOAP format), e.g., S ¼ Subjective observations, O ¼ Objective observations, A ¼ Assessment, and P ¼ Plan (Herbert et al. 2006). Documents such as PPR, MAP, and other practice-specific forms will be retained to support the pharmacist in maintaining consistent professional documentation. This consistent document is helpful to facilitate teamwork among healthcare team members as per organizational or regional variations (Rivera et al. 2020).

12.7

Role of Clinical Pharmacist in Institution-Based Patient Care

The policies and procedures in institutional settings are slightly different from those represented for ambulatory settings. In these settings, clinical pharmacists are also actively involved in the selection of medicine as part of the medical care team.

12.8

Challenges for Pharmacy Transition to Clinical Care

Optimizing the role of a pharmacist in patient care has been the modern focus of the pharmacy field. The recent introduction of the PharmD course in the pharmacy education is one of the breakthrough achievements in this regard. The perception of pharmacy profession is changing in the society. The role of pharmacist has reached beyond the stage of compounding and dispensing of medicines to drug intervention and DTM for patient care in the hospital setup. In spite of recent changes in the trend of the pharmacy profession, there are some barriers observed in the effective implementation of pharmacist-led DTM. The barriers include lack of awareness among the public about the range and benefits of the clinical services which a pharmacist can offer, lack of more structured pathway for development of new models of patient care, poor integration of community pharmacists into local clinical teams, and lack of knowledge among other healthcare professionals about the

12

Medication Therapy Management: Importance and Practice

229

potential impact, which a pharmacist can have on the patient’s medicine management (Monson et al. 1981).

12.9

Overcoming the Barriers: What Need to Be Done?

Raise awareness of clinical services provided by pharmacists, such as counseling on mild and severe illnesses, prescribing suggestions, support in the management of long-term conditions such as asthma, hypertension, diabetes, etc., and public health interventions such as smoking cessation, weight management, etc. There is a muchfelt need in hospital, clinical, and community settings that the regulators frame policies regarding the implementation of pharmaceutical services in the local clinical teams and the impact of pharmacists to make the healthcare and medication therapy management more efficient, and it should be stressed upon. It’s high time that pharmacists recognize the need to shift their attention away from only dispensing and supplying medicines toward providing a broader range of services keeping the ultimate goal of helping patients get the most benefit from their medicine and maintain health. In India, it is difficult for drug to achieve the same extent of action and activity in the population as compared to some other individual. The reason behind this is multicultural and wide genetic diversity of India. The individualization of drug therapy concept states that two individuals could not show the same response to the same drug under similar disease condition attributed to different personal profile and health factors. Drug therapy customization as per patient need is the important task where the role of pharmacist comes into light. Professionals with PharmD degree are trained in this area and very much required in India to attain better control over drug use and compliance among patients.

12.10 Some Examples 12.10.1 Medication Therapy Management 1. MirixaPro is an MTM learning and practicing software. 2. Academician in pharmacy need to educate the pharmacy students about the significance of MTM as the use of prescription and nonprescription medications increases tremendously. Technology-laden training of pharmacy is necessary. MirixaPro is the platform available as a resource for students training in medication therapy management. 3. Involvement of MTM in internship activities is restricted. MTM should also be the important part in community pharmacy practice. Students must be educated and trained in producing MTM by involving it in classroom curriculum and developing the skills as well as knowledge required for it. 4. One can add flags to further enhance the learning skills in MirixaPro.

230

A. N. Nagappa and J. Kanoujia

5. The course of PharmD provides the knowledge about drug-disease interactions, inappropriate dosing regimens, drug-drug interactions, and therapeutic duplications. Student exposure to specific design cases is still very limited, and it affects their ability to deal with therapeutic issues. Focus is required in developing critical thinking and problem-solving abilities. 6. Software has web support through which one can review the MTM provided as a case study. This makes student to learn and update the skills by providing MTM learning. 7. Young pharmacists must provide direct patient care to improve patient outcomes via improving patient medication therapy and reducing adverse events. Patient interview and MirixaPro, a technology-based platform, provide a student to experience MTM before starting the practice of clinical pharmacy. The training on MirixaPro program improved students’ MTM performance in general and enhanced their comfort level about patient interviews.

12.10.2 Acetaminophen-Induced Hepatotoxicity 1. An old male aged 59 with height 50 800 and weight 160 lbs. complains nausea and emesis. The patient was slightly flushed (99.4F) and also showed left upper abdominal tenderness with sign of mild hepatomegaly and mild sclera icterus. The patient was moderately alcoholic with regular intake of alcohol 10 to 12 drinks per week for the past several years. He got a knee injury, and to treat this, he has taken approximately eight tablets of Extra Strength Tylenol containing 500 mg acetaminophen every day for the past 2 weeks as pain reliever. 2. Increased level of serum ALT (535 IU/L) and AST (430 IU/L) with reference of normal values (ALT ¼ 4–51 IU/L and AST ¼ 15–45 IU/L) is found in laboratory analysis with 41 μmol/L of bilirubin (normal: < 17 μmol/L) and 2.0 mmol/L of a serum glucose level (normal: 3.9–5.8 mmol/L). The concentration of acetaminophen in blood was found to be 58 μg/mL. The patient was admitted to the hospital and administered an intravenous infusion that included glucose and N-acetylcysteine (NAC).

12.11 Discussion 1. Acetaminophen is basically known as paracetamol which is a very common ingredient of various formulations such as Excedrin, Vicks, Tylenol, Midol, Comtrex, etc. It is used as analgesic in the United States, even if it is hepatotoxic. Overdose of acetaminophen is a major reason of acute liver failure (ALF), accounting for approximately 50% of all cases of ALF. 2. As per one study in 2015, 48% of acetaminophen-induced ALF cases were unintentional, and 42% of acetaminophen-induced ALF occurred in individuals who were trying self-harm or suicide. Moreover, it was seen that the patient

12

3.

4.

5.

6.

7.

Medication Therapy Management: Importance and Practice

231

taking therapeutic dose of acetaminophen also presented the issue of hepatitis and ALF. N-acetyl-p-benzoquinone imine (NAPQI) is a highly unstable, reactive, and toxic metabolite which is the reason for hepatotoxicity. At therapeutic dose, majority of the acetaminophen is metabolized by glucuronidation (63%) and sulfation (34%) reaction in the liver. Very smaller amount (less than 5%) is by the cytochrome P (CYP)-450 system to NAPQI and water-soluble metabolite excreted in urine. A person who consumes moderate amount of alcohol daily or taking CYP-450 inducer drugs (phenytoin, phenobarbital, etc.) also presented the accumulation of NAPQI at toxic level. Fasting and malnutrition also increase the risk of ALF. The single adult acetaminophen dose should not exceed 650 mg (significantly less than the 1000 mg available in 2 OTC tablets). 1000 mg dose of acetaminophen should be available only by prescription. The maximum total daily recommended dose should be decreased to 2600 mg/day. Acetaminophen containing prescription product should be discontinued in combination with other pain medications such as Lortab, Vicodin, Endocet, and Percocet. Abovementioned patient was treated with glucose and NAC. Glucose is administered to balance the hypoglycemic condition, and NAC works to replenish the glutathione stores needed for NAPQI conjugation in the liver. Acetaminophen overdose is always managed by the use of activated charcoal, induction of emesis, and gastric lavage. Hepatic damage can be minimized if intravenous N-acetylcysteine (NAC) is administered within 8–10 hours after acetaminophen ingestion (https://primeinc.org/casestudies/pharmacist/study/1105/Acetamino phen-Induced_Hepatotoxicity).

12.12 Documenting in Pharmacy-Based Patient Care Services Documenting is the important element in pharmacy-based patient care service to increase service outcome as well as knowledge of patients about his/her care. Documentation involved the maintenance of patient records which is helpful in billing purposes, reimbursement purposes, protecting against professional liability, and analysis of patient outcome data (https://www.pharmacist.com/sites/default/ files/files/mtm_documentating_pc_services.pdf).

12.13 Conclusion Pharmacy practice is a novel initiative in developing countries whereas it is wellestablished practices in developed countries for comprehensive treatment and monitoring. This can be achieved by MTM which can be given in the model home-based patient counseling and monitoring. The adoption of digital products like MirixaPro has revolutionized the MTM.

232

A. N. Nagappa and J. Kanoujia

References American Pharmacists Association and National Association of Chain Drug Stores Foundation (2008) Medication therapy management in community pharmacy practice: core elements of an MTM service (version 2.0). J Am Pharm Assoc 48(3):341–353 Begley KJ, Coover KL, Tilleman JA, Ryan Haddad AM, Augustine SC (2011) Medication therapy management training using case studies and the MirixaPro platform. Am J Pharm Educ 75(3): 49. https://doi.org/10.5688/ajpe75349 Botermann L, Krueger K, Eickhoff C, Kloft C, Schulz M (2016) Patients' handling of a standardized medication plan: a pilot study and method development. Patient Prefer Adherence 10:621–630. https://doi.org/10.2147/PPA.S96431 Bouvy JC, De Bruin ML, Koopmanschap MA (2015) Epidemiology of adverse drug reactions in Europe: a review of recent observational studies. Drug Saf 38(5):437–453. https://doi.org/10. 1007/s40264-015-0281-0 Deshpande Prasanna R, Kazim SM, Pawar Atmaram P (2018) Functioning and productivity of Jan Aushadhi stores in India: the owners' perspective. J Health Res 5(1):28–37 Ferreri SP, Hughes TD, Snyder ME (2020) Medication therapy management: current challenges. Integr Pharm Res Pract 9:71–81. https://doi.org/10.2147/IPRP.S179628 Herbert KE, Urmie JM, Newland BA et al (2006) Prediction of pharmacist intention to provide Medicare medication therapy management services using the theory of planned behavior. Res Social Adm Pharm 2(3):299 Hohmeier KC, Wheeler JS, Turner K et al (2019) Targeting adaptability to improve medication therapy management (MTM) implementation in community pharmacy. Implementation Sci 14: 99. https://doi.org/10.1186/s13012-019-0946-7 Huiskes VJB, Burger DM, van den Ende CHM et al (2017) Effectiveness of medication review: a systematic review and meta-analysis of randomized controlled trials. BMC Fam Pract 18:5 Lounsbery JL, Green CG, Bennett MS et al (2003) Evaluation of pharmacists’ barriers to the implementation of medication therapy management services. J Am Pharm Assoc 49(1):51–58 Mendonça S, de Medina A, Cristine MA, Pereira, Coelho GC, Santos, de Souza DM, dos Serio G, Sousa EB, do Carmo Vilas Boas M, de Oliveira DR, Soares AC (2016) Clinical outcomes of medication therapy management services in primary health care. Braz J Pharm Sci 52(3): 365–373 Monson R, Bond CA, Schuna A (1981) Role of the clinical pharmacist in improving drug therapy: clinical pharmacists in outpatient therapy. Arch Intern Med 141(11):1441–1444 Pellegrino AN, Martin MT, Tilton JJ, Touchette DR (2009) Medication therapy management services: definitions and outcomes. Drugs 69(4):393–406 Powers MF, Bright DR (2008) Pharmacy technicians and medication therapy management. J Pharm Technol 24(6):336–339 Ramalho de Oliveira D, Brummel AR, Miller DB (2010) Medication therapy management: 10 years of experience in a large integrated health care system. J Manag Care Pharm 16(3):185–195 Rivera J, Shcherbakova N, Vala C, Capoccia K (2020) Community pharmacists' interventions and documentation during medication therapy management encounters delivered face-to-face versus via telephone: the devil is in the details. Res Social Adm Pharm 16(10):1447–1451 Sharma M, Majumdar PK (2009) Occupational lifestyle diseases: an emerging issue. Indian J Occupation Environ Med 13(3):109–112. https://doi.org/10.4103/0019-5278.58912

12

Medication Therapy Management: Importance and Practice

233

Smith MG, Ferreri SP, Brown P, Wines K, Shea CM, Pfeiffenberger TM (2017) Implementing an integrated care management program in community pharmacies: a focus on medication management services. J Am Pharm Assoc 57(2):229–235.e1. https://doi.org/10.1016/j.japh.2016. 12.074 Stafford R, Thomas J, Payakachat N et al (2017) Using an array of implementation strategies to improve success rates of pharmacist-initiated medication therapy management services in community pharmacies. Res Social Adm Pharm 13(5):938–946 Ventola CL (2018) Big data and pharmacovigilance: data Mining for Adverse Drug Events and Interactions. P & T 43(6):340–351 Zeng K, Bodenreider O, Nelson SJ (2008) Design and implementation of a personal medication record-MyMedicationList. AMIA. Ann Symp Proc AMIA Symp 2008:844–848

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

13

A. N. Nagappa and Jovita Kanoujia

Abstract

In order to manage minor ailments and to get symptomatic reliefs, patients prefer to consult community pharmacist. Community pharmacists after quickly assessing the patient conditions advise whether patient needs to be hospitalized or to consult a doctor. Community pharmacists are also involved in advising and dispensing OTC medicine resulting in reduction of doctors and hospitals burden. By doing so, community pharmacist reduces the burden on doctors and hospitals. The patient also benefited through hospitalization and referrals. Keywords

OTC abuse · Food-OTC interaction · Multivitamin abuse · Antacid abuse · Informed self-medication

13.1

OTC Medicines

It is not always possible to consult a doctor or visit a hospital for all day-to-day health needs. As we know, doctors in hospitals are always busy in attending patients with serious healthcare issues. Prior booking for an appointment to consult a doctor is a usual practice worldwide. During consultation, a doctor makes observation of the patient and also asks for some diagnostic tests to be performed. Doctors usually follow a standard protocol through which he/she arrives at a diagnostic probability of the patient conditions. After the doctor gets ensured about the patient conditions, he/she starts intervention either he will admit the patient in the hospital/nursing home or he may treat the patient in outpatient department (OPD). For outpatient A. N. Nagappa · J. Kanoujia (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_13

235

236

A. N. Nagappa and J. Kanoujia

department patients, doctors usually prescribe medicines and let the patient go home. The medicines prescribed by the doctors aim at symptomatic relief or cure of the condition of the patients. This facility is usually availed by the patients who are undergoing severe disease conditions or having emergency situations (Aronson 2004). There are large numbers of patients who suffer from minor ailments like cough, common cold, headache, body ache, dyspepsia, or diarrhea. Although they are called as minor elements, the pain and suffering of the patient who undergoes minor ailments make them to avail medical aid. They usually depend upon community pharmacy to resolve their conditions for an immediate relief. The pharmacist is well trained in identifying and judging the patient conditions, whether the patient condition necessitates a hospitalization or the condition of the patient either is serious enough to consult a doctor or can be treated with over-the-counter medicines in pharmacy itself. Hence, every pharmacist should be able to differentiate the patient condition as minor ailments or serious disease (Bhattacharya 2004). Pharmacists are natural custodians of medicines and are supposed to protect the community from adverse drug reactions (ADR) of medicines by restricting the easy access of medicines to the patients and health consumers (P&HC). Community pharmacist, as a responsible healthcare professional, does not engage in hawking of drugs to the public as he is bound by professional ethics. Community pharmacists are interested in protecting the innocent patients and health consumers from ill effects of the drugs by irrational use and self-medication. It is very well established that all drugs carry a burden of side effects on patient and health consumers. If there is mismatch or irrational dispensing and wrong administration, it can cause serious health problems to the user. It is also important to update the patient’s knowledge regarding the scope and limitation of the drugs in relieving symptoms and curing medical conditions. One should always remind the patients not to develop overdependence on drugs but to use it as the last option to overcome the suffering and condition under the advice of medical professionals. The patients should never use medicines on their own, as this would affect their health in the long run. The patients should be sensitized about lifestyle modifications and diet in order to ensure good health. The risks of adverse drug effects are always a cause of concern for the patients. The patients have to practice self-management of their condition instead of self-medication. It is possible by engaging patients on a continuous education by healthcare providers especially community pharmacist (Sansgiry et al. 2016; Brass 2001). Drugs are intermediate instruments which can help patients to avoid suffering or regain health by making corrections in the body. For example, drugs used for pain management can relief the pain by inhibiting the synthesis of pain and inflammatory mediators. The duration of drug effects depends upon its blood concentration, and every drug undergoes absorption, distribution, metabolism, and excretion process, and its residence time depends upon its pharmacokinetic profile which affects its pharmacodynamic actions. Once the blood concentration of the drug falls below minimum effective concentration, the drug effects start fading out. If the pain conditions still persist, then the patient needs to take one more dose of the drug.

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

237

The information about drugs is very vast and confusing. Although health information technology has developed databases of existing drugs by online updating, it is not feasible by a patient himself/herself to treat even the minor ailments. The easy accessibility of the pharmacist to the P&HC makes them rush to the pharmacy first and seek for relief from suffering conditions. Pharmacists are custodians of all types of medicines like prescription-only medicines, narcotic drugs, alcohol-based formulations, and over-the-counter medicines. All types of medicines are likely to be abused by the public. Storage, sale, and dispensing of medicines are under the authority of the pharmacist. Prescription-only medicines and narcotic drugs should be dispensed to the patients on a prescription by a registered medical practitioner. However, the over-the-counter medicines can be dispensed to the patients by the pharmacist without a prescription under the informed selfmedication. It can be dispensed on requests of P&HC. In case the pharmacist has suspicion about the abuse of over-the-counter medicine dispensed, then the pharmacist can refuse to dispense such medicine to the patient. There are cases of abuse of cough syrups like phensidyl and Corex as hallucinogenic agents by the addicts. The pharmacist has an important role in preventing abuse of drugs in the society. It is the duty of every pharmacist to be vigilant about the sale of drug which is likely to be abused by the public. In case it comes to the notice of a pharmacist, he must not hesitate or delay in raising the alarm and alerting the concerning authorities and should curb the menace before it grows into a big racket (Sweileh et al. 2004). Drug addiction itself is a major disease. It needs to be treated in a hospital. Hence, when P&HC frequently visit pharmacy with or without prescription for a suspected drug causing addiction, he/she must be referred to the social welfare department who are engaged in de-addiction activities in a community. Over-the-counter medicines are not prescription medicines and are not in the list of schedule H, H1, C, and C1 drugs. They also are not regulated by Monopolies and Restrictive Trade Practices Act (MRTP Act) or by the Narcotic Drugs and Psychotropic Substances Act. The medicines are known for having a wide range of safety. They are used for day-to-day management of some minor ailments and other mild conditions. Over-the-counter medicines can be dispensed by a pharmacist for treatments of minor ailments to patients who visit the pharmacy to get relief. Pharmacists have a dialogue with the patient. The pharmacist is able to resolve the patient condition with over-the-counter medicines. The pharmacist while dispensing over-the-counter medicines takes the responsibility of patient counseling and educating the patients in the matters of safe practices. He/she may also alert the patient if there are any expected side effects or going to result by taking over-the-counter medicines. Patients are to be cautioned to avoid driving of vehicles or working on machineries which may happen due to drowsiness caused by some medicines. The accident or mishaps may result to death or serious injury leading to amputation of the hands or limbs making them physically handicapped. This is preventable if the pharmacist is alert and advises patients regarding feeling of drowsiness and sleeping after consuming the medicine for couple of hours. The over-the-counter medicines also offer the community pharmacist to practice pharmacy. He/she can also charge service fee

238

A. N. Nagappa and J. Kanoujia

from the P&HC. This can be an additional source of income for the community pharmacist (Cooper 2013). A survey in 2015 found that 52% of people practicing self-medication were doing so due to the lack of time to visit a doctor, wanting to save on consultation fee, and reliance on the Internet and pharmacist for the resolution of health issues. The pharmacist is easily accessible and does not charge any consulting fee. He gives away them the appropriate medicines for ailments like allergies, cold, cough, nasal congestion, fever, pain, diarrhea, hyperacidity, and most skin-related conditions. Paracetamol is a classic example of over-the-counter medicine. Worldwide it is used in conditions like fever and pain. It has a wide margin of safety with effectiveness as a pain and fever reliever. In 2016, the over-the-counter market grew at an 8% culminating to 2.7 billion dollars in India itself. Over-the-counter (OTC) medicines, which can be purchased and used without consulting a doctor, are the key point for growth rate worldwide. However, over-thecounter medicines cannot be allowed without control of drug laws. Hence, the Government of India is soon coming out a gazetted notification for regulation of over-the-counter medicines. OTC medicines in India are deficient with appropriate label. It becomes very difficult for patients and health consumers to use that medicine confidently because the vital information about the purpose of medicine, the active and inactive ingredients used in the formulation, information about how to use the medicine, and safety instructions while using the medicine are missing on labels. However, in India, pharmacists in the drug shop do not have the latest knowledge about medicine and are not updated with the new information. Pharmacists are more focused in drugstore management rather than pharmacy practice. This makes a big difference while using medicines in the society. The recommendation of registered pharmacist is taken seriously by the patients. It is also suspected under the pretext of over-the-counter medicines. Pharmacists indulge in dispensing of prescription medicines which is illegal and dangerous. Due to the absence of surveillance and implementation of rules by the regulatory agencies, the illegal sale of prescription drugs is very much rampant. It is illegal to dispense prescription medicines to patients without having any medical knowledge about the patient’s conditions. Pharmacists are generally doing so because they get more margins on sale of medicines. The pharmacist gets less money when they dispense medicines against prescription. For example, antibiotic are handed over to patient freely for a long time without a prescription. This is the major cause of the emergence of antimicrobial resistance on a large scale (Marathe et al. 2020). As a policy, over-the-counter medicines are supposed to be used for minor ailments and should be used for a brief time. However, we see many patients indulging in long-term self-medication of over-the-counter medicines. In 2016, the Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) has complained to drug controller general of India about rampant misuse of steroid creams and antifungal agent which cause serious side effect to the patient. Topical preparations of steroids get easily absorbed through the skin and show systemic effects and interfere with homeostasis of internal hormonal mechanism. This causes serious adverse side effects of steroids like oily skin, severe acne, liver disease (liver

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

239

tumors and cysts), hair loss, kidney disease, heart disease (stroke and heart attack), irritability, altered mood, depression, and increased aggression (Wazaify et al. 2005; Jacobs et al. 2019).

13.2

Steroids Are Abused in the Self-Medication Mode for the Following Conditions

The science of steroid abuse results in paranoia, enlargement of the breast in men, acne, facial hair growth (in women), rapid muscle/weight gain, and hyperactivity. Long-term steroid abuse can lead to serious health issues and even permanent health hazards like liver damage, kidney problems or failure, high blood pressure, enlarged heart, and changes in blood cholesterol. Government bans over-the-counter sale of skin medications containing hydroquinone. Dermatologists call for stricter regulatory watch. Pharmacies in the country have to stop selling topical products containing hydroquinone. Hydroquinone is a bleaching agent mainly used for reducing skin pigmentation. The Health Ministry has imposed the ban on over-the-counter sale of these products to curb their indiscriminate use. Hydroquinone is also termed as benzene-1,4-diol or quinol. It is mainly found in skin lightening creams, bleaching creams, pigment gels, and antiaging products. Currently, several hydroquinone-containing depigmenting creams are available in Indian markets and can be procured online. Depiwhite from Wockhardt and Melalite 15 cream from Abbott are very common products available in India (Hoffman and Ratamess 2006; Kanayama et al. 2009; Mistry et al. 2011). The amendment of the Drugs and Cosmetics (D&C) Rules of 1945 to bring hydroquinone-containing ointments under Schedule H will come into force. The drug advisory body on technical matters recommends the government to take strict action against this product. The Ministry of Health and Family Welfare had involved all steroid-containing skin products under Schedule H of the Drugs and Cosmetics Act to restrict their over-the-counter sale. Hydroquinone-based skin products are also added to the list due to the rise in several cases of adverse effects like redness, rashes, and inflammation and its unchecked sale. The government has brought all steroid-laced creams under Schedule H following a public interest litigation filed in the Delhi High Court by IADVL, seeking a ban on the manufacture and sale of skin creams containing potentially harmful ingredients. However, regulating sales is not enough in the case of steroid ointments. The government should outrightly ban all irrational combinations. These creams are often used without medical guidance for itching, acne, minor infections, and fairness, and even beauticians recommend them. It is important that long-term use of medicines for skin problems must be under the prescription from a qualified doctor. Hydroquinone-containing medications should not be sold over the counter; they must be used only for serious skin ailments. Creams containing steroids/hydroquinone or other similar medicines are not permitted to be manufactured or sold in the developed countries. Several countries

240

A. N. Nagappa and J. Kanoujia

Table 13.1 Brand medicines with example Medicine Antacids and acid reducers

Antiemetic medicines Antidiarrheal Antihistamines Cough medicine Decongestants Herbal products and supplements Laxatives Painkillers Vitamins

Examples Aluminum hydroxide, magnesium carbonate, sodium bicarbonate, calcium carbonate, simethicone, ranitidine, famotidine Dimenhydrinate, diphenhydramine, meclizine, promethazine Loperamide, subsalicylate Brompheniramine, cetirizine, chlorpheniramine Expectorants, dextromethorphan, guaifenesin Oxymetazoline, phenylephrine

Brand names Alkalizer, AlternaGEL, Amphojel, Milk of magnesia, tums, Gelusil, Maalox, Pepto-Bismol, Gaviscon, Mylanta, Rolaids Subsalicylate, Kaopectate, PeptoBismol Imodium, Kaopectate Dimetane, Zyrtec, Chlor-Trimeton Robitussin, Triaminic, Mucinex Afrin, Dristan, Vicks Sinex, Sudafed PE

Cranberry, saw palmetto, soy, garlic, gingko Methylcellulose, psyllium Liquid petrolatum Vitamin A, D, E, C

Citrucel, Metamucil Colace, Surfak, mineral oil Darwin

such as Japan, the USA, and Australia have either prohibited or enforced regulations on the counter sale. Hydroquinone is also added to the list now after reporting several cases due to over-the-counter sales. There are strict regulations of counter sale. In India, there is a lack of well-defined legal and policy framework of counter sale. Hydroquinone is also added to the list now after several cases reported. As such, neither the Drugs and Cosmetics Act 1940 nor the Drugs and Cosmetics Rules 1945 defined OTC medicines (Dey 2014; Saraswat et al. 2011). Recently, the Government of India through the Union Health Ministry is planning to make an exclusive schedule for over-the-counter drugs in the country. A subcommittee constituting three members has been formed by the Drugs Consultative Committee of the Ministry under the chairmanship of Haryana State drug controller. The aim of the committee is to define counter sale. Hydroquinone is the drug also added in the list after several cases reported due to sale in the country without prescriptions. However, a separate category of counter sale is also required. In India, many drugs (mainly allopathic drugs) which are regarded as safe to sell without prescription mostly come under Schedule H and H1 and sometimes also require a prescription as per D&C Act 1940 and Rules 1945. Once the subcommittee report is finalized, the government is expected to introduce a new category of counter sale. Several cases reported for the medicines include antiemetic, antipyretic, and anti-allergy drugs easily dispensed by pharmacists without a prescription. The list may also include decongestants, antacids, muscle relaxants, external preparations for the skin, anti-inflammatory drugs, and hormonal contraceptives. Several cases of medicines with example and brand names are given in Table 13.1.

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

13.3

241

Case Study

13.3.1 Medication Issues with Common Cold Remedies Ram Krishna (RK, 58 years old), a telemarketing employee, had a history of heart disease. RK was suffering from sore throat, runny nose, fatigue, headache, and sneezing issues during influenza season in his area. He was advised by his supervisor to take rest to relieve the symptoms like common cold. On the way home, Mr. RK purchased over-the-counter medicine (oral decongestant) containing pseudoephedrine from the pharmacy to relieve his symptoms. After taking the same medicine, Mr. RK’s symptoms were improving, but other problems arise like dizziness, dry mouth, trouble in sleeping, and nervousness with extreme tachycardia. He immediately visited a cardiologist for checkup, but there were nothing serious issues with the heart. Mr. RK informed the doctor about his over-the-counter cold medicine, and unfortunately, that medicine (decongestant) was found to cause heart-related issues. After discontinuation of the medicine, cardiac-related symptoms were slowly vanished. The doctor has informed Mr. RK about his over-the-counter decongestant medicine and called him to give patient education about the common cold. He explained that common cold is a disease infecting adult two to four times average per year. It is a viral infection with contagious nature mainly affecting the nose and throat, caused by viruses like rhinovirus and coronavirus. After catching the infection, symptoms appear within 1–2 days in approximately 50% of people. Symptoms usually last 3–5 days. The first symptom is commonly a sore throat followed by coughing, nasal congestion, sneezing, runny nose, headache with mild fever, as well as fatigue. All these symptoms can be treated with over-the-counter medicines containing multiple drug substances. Pseudoephedrine is a drug mostly used to relieve cold, sinus congestion, fever, and allergy-related nasal discomfort. This drug comes under the category of sympathomimetic which is used as nasal decongestant by causing narrowing of the nasal blood vessels. This drug is available as tablet, extended-release tablet (12-h release), chewable tablet, solution, and 24-h extended-release tablet. Twenty-four-hour extended-release tablets are taken once a day (should not exceed more than one dose in 24 h), 12-h extended-release tablets are taken every 12 h interval (should not exceed more than two doses in 24 h), and regular tablet, solution, and chewable tablet are recommended at every 4–6 h interval. The drug works by constricting blood vessels in swollen tissues of the nose and drying of secretions. This tightening of blood vessels for all types of blood vessels in cardiac patient increases heart rate and blood pressure and reduces the blood flow with the symptoms of heart palpitation. That is why, Mr. RK was also feeling the nervousness, dizziness, dry mouth, and sleep disturbance with tachycardia.Another important aspect in the treatment of viral infection is not to use antibiotics as causative agent is virus not bacteria. Additionally, antibiotics are also responsible in killing good bacteria leading to other issues. Nasal congestion in common cold can be relieved by using pseudoephedrine/phenylephrine or an antihistamine. Regular analgesics are helpful to

242

A. N. Nagappa and J. Kanoujia

relieve sore throat. Dextromethorphan/guaifenesin can be used to treat a cough and chest congestion. In the treatment of cardiac patient, medicine without decongestants should be selected. Medicines with antihistamine, pain reliever, and cough suppressant are good choice. Nasal spray is also helpful to treat nasal blockage. Nasal spray containing decongestants, not causing any side effect and work by narrowing the blood vessels in only nasal cavity. It causes very less side effect, but frequent use of topical decongestant is not recommended as it can cause drying in the nose, burning, stinging sensation, sneezing, and increase in nasal discharge. Adopting the natural treatment is a good idea to treat cold like using eucalyptus oil vapors to loose the phlegm, licorice to soothe the sore throat, etc.If the patient condition is not manageable, then again visit the doctor for his opinion. Yearly vaccine for flu should be taken by elderly patient, healthcare workers, and people with chronic ailments like diabetes, cardiac issues, etc. There are prescription medications available to treat influenza, such as Symmetrel®, Flumadine®, Relenza®, and Tamiflu®. Now, RK gets back on his job again with sufficient knowledge regarding treatment and caution about common cold. After his counseling, now he becomes very conscious about over-the-counter medicine and stated reading the product leaflet whether the medicine was contraindicated in cardiac patient or not (https:// primeinc.org/casestudies/pharmacist/study/521/Medication_Issues_with_Com mon_Cold_Remedies).

13.4

Case 2

13.4.1 Effects of Dietary Supplements in Adults Taking Cardiovascular Drugs Mrs. Anuradha (AR), a 76-year-old woman suffering with peripheral artery disease, hypertension, and lower extremity edema, visits her cardiologist. Her major complaint is her high blood pressure (BP) and associated fatigue. On examination at home, it was found that her systolic blood pressure (SBP) ranges from 140 to 200 mm Hg and diastolic BP ranges from 70 to 104 mm Hg. Her height is 50 200 and weight is 79.3 kg. Her body mass index (BMI) is 32, and her waist circumference is 3600 with a pulse of 70. Her BP raised in the office at 160/84 mm Hg, even with repeated readings. Her medications include the following: • • • • • • •

Olmesartan 20 mg every bedtime Aspirin 81 mg once a day Metoprolol XL 50 mg twice a day Ezetimibe 10 mg/simvastatin 40 mg once a day Furosemide 40 mg once a day Clopidogrel 75 mg once a day Clonidine 0.2 mg 4 times a day and as needed

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

243

In spite of taking these medications, her BP always found to be high. She is trying to adhere with her diet but admits sometimes not able to stick with diet plan. She also complains of sessions of headaches with facial redness (both symptoms are signal of severe rise in BP). To teat BP, she takes clonidine (0.2 mg) four times a day. She goes on to relate that she has been doing some reading on supplements and vitamins and is interested in taking garlic supplements, omega-3 fatty acids, and vitamin E. She says that garlic supplements claim to lower blood pressure, omega-3 fatty acids have anti-inflammatory properties, and vitamin E is good for the heart among other benefits.

13.5

Discussion

Complementary and alternative medicine (CAM) is defined as any preventive and therapeutic agent not considered a part of standard pharmaceutical medicine, including dietary supplements. The use of such therapies has risen considerably over the last few decades both in the general population and in patients with cardiovascular disease (CVD). Nearly 66% of all people diagnosed with heart failure or other CVD including hypertension report using complementary and alternative medicine. These patients are therefore at increased risk for side effects from interactions with the complementary and alternative medicine and prescribed pharmaceutical agents as well as nonadherence that could occur when taking multiple medications. Alternatively, adding complementary and alternative medicine to conventional cardiovascular drug regimens may offer potential benefit that remains unknown. Although there is a significant amount of research available detailing drug-drug interactions in diverse populations, specific data for drug-supplement interactions or additive supplement effect is lacking in the CVD population. Patients and healthcare professionals alike should remember that complementary and alternative medicines are not regulated as prescription drugs. The standards that prescription drug manufacturers are held to for providing evidence of efficacy and safety are not met by most manufactures of complementary and alternative medicine since most do not require DCGI approval. The DCGI also does not require evidence of purity, quality, or composition prior to marketing of the majority of complementary and alternative medicine. Thus, there is a significant absence of standardization of these products on the market and even among products from a single manufacturer: • No additional benefit for high-density lipoprotein cholesterol (HDL-C) with the addition of coenzyme Q10 to fenofibrate. • Favorable benefits for HDL-C with the addition of garlic to warfarin and garlic to nitrates. • No additional benefit for HDL-C or low-density lipoprotein cholesterol (LDL-C) with the addition of omega-3 fatty acids to certain statins. • Favorable benefits to triglyceride levels and systolic BP but no additional benefit to diastolic BP with the addition of omega-3 fatty acids to certain statins.

244

A. N. Nagappa and J. Kanoujia

• Favorable benefits to triglyceride levels and LDL-C with combinations of omega3 fatty acids and acetylsalicylic acid and dipyridamole. • Favorable benefits to LDL-C and triglyceride levels were noted for combinations of vitamin E and nifedipine. • Vitamin K led to favorable outcomes in combination with coumarin derivatives on LDL-C, triglyceride levels, percent time in the international normalized ratio (INR) therapeutic range, and variability of INR. According to the AHRQ review, more research needs to be conducted on interactions between specific cardiovascular drugs and complementary and alternative medicine. Additionally, stricter regulation on the manufacturers of complementary and alternative medicine to verify biological activity and side effects of these medications will help consumers make better choices and aid physicians in guiding their patients to make more informed health decisions (https://primeinc.org/ casestudies/pa_np/study/977/Effects_of_Dietary_Supplements_in_Adults_Taking_ Cardiovascular_Drugs).

13.6

Conclusion

Over-the-counter medications came into practice out of necessity when patients are unable to approach doctor for minor ailments. The community pharmacist due to his knowledge in drugs and diseases became friend with patients and health consumers by helping them to manage or mitigate conditions like cough and cold, diarrhea, hyperacidity, headache, and many other mild conditions. Patients and health consumer soon realized that the community pharmacist is easily accessible and does not cost like doctors. Mild conditions are bothersome, and patient needs a person who can help him out to resolve his suffering. The community pharmacist is well organized to help the patients. He can assess the patient condition and advise the patients whether the condition mandates to see a doctor or to get admitted in a hospital. The community pharmacy has its own list of nonprescription medicines which he/she dispenses to the patients depending on the requirement of the patient. This he reduces the patient rush to the clinics, thus lessening the burden of doctors and healthcare system. By nature, OTC medications have a wide margin of safety and can be easily administered without much sophistication. They are usually in oral dosage forms (tablets, capsules, or liquid orals) and externally used preparations like creams, ointments, and topical preparations. They are nonprescription medicines which are usually used in primary care of patients. Pharmacists usually get remunerated by the margin on sale of the medicines and do not charge additional fee or consultation fee to the patients. The range of OTC medications is extended to nutraceuticals and cosmeceuticals. There are many herbal medicines which are recommended to patients for use to mitigate several mild conditions. OTC medication formulations may also be available as ethical product (prescription medicine), for example, chlorpheniramine tablet for the treatment of allergic itching. Usually, OTC

13

Over-the-Counter Medicine: Community Pharmacy and Informed Self-Medication

245

medication shall be in lower-dose range, and prescription medicine of chlorpheniramine may contain therapeutic recommended dose. In recent times, it has been observed OTC medications are also likely to be abused, for example, the use of iodine ointment for psychedelic purposes. Codeine cough syrup, chlorpheniramine syrup, etc. are used abusively for hallucinations by mixing with alcohol beverages. There are also several cases of suicide attempts by consuming paracetamol tablets. Although it is well known for a wide margin of safety, it is also true that people have abused to commit suicide.

References Aronson JK (2004) Over-the-counter medicines. Br J Clin Pharmacol 58(3):231–234. https://doi. org/10.1111/j..2004.02191.x Bhattacharya S (2004) Heart wonder drug goes over-the-counter. New Sci 16:35 Brass EP (2001) Changing the status of drugs from prescription to over-the-counter availability. N Engl J Med 345(11):810–816 Cooper RJ (2013) Over-the-counter medicine abuse - a review of the literature. J Subst Abuse 18(2): 82–107. https://doi.org/10.3109/14659891.2011.615002 Dey VK (2014) Misuse of topical corticosteroids: a clinical study of adverse effects. Indian Dermatol Online J 5(4):436–440. https://doi.org/10.4103/2229-5178.142486 Hoffman JR, Ratamess NA (2006) Medical issues associated with anabolic steroid use: are they exaggerated? J Sports Sci Med 5(2):182–193 Jacobs TG, Robertson J, van den Ham HA et al (2019) Assessing the impact of law enforcement to reduce over-the-counter (OTC) sales of antibiotics in low- and middle-income countries; a systematic literature review. BMC Health Serv Res 19:536. https://doi.org/10.1186/s12913019-4359-8 Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG Jr (2009) Anabolic-androgenic steroid dependence: an emerging disorder. Addiction 104(12):1966–1978. https://doi.org/10.1111/j. 1360-0443.2009.02734.x Marathe PA, Kamat SK, Tripathi RK, Raut SB, Khatri NP (2020) Over-the-counter medicines: global perspective and Indian scenario. J Postgrad Med 66(1):28–34. https://doi.org/10.4103/ jpgm.JPGM_381_19 Mistry N, Shapero J, Kundu RV, Shapero H (2011) Toxic effects of skin-lightening products in Canadian immigrants. J Cutan Med Surg 15(5):254–258 Sansgiry SS, Bhansali AH, Bapat SS, Xu Q (2016) Abuse of over-the-counter medicines: a pharmacist's perspective. Integr Pharm Res Pract 6:1–6. https://doi.org/10.2147/IPRP.S103494 Saraswat A, Lahiri K, Chatterjee M, Barua S, Coondoo A, Mittal A et al (2011) Topical corticosteroid abuse on the face: a prospective, multicenter study of dermatology outpatients. Indian J Dermatol Venereol Leprol 77:160–166 Sweileh WM, Arafat RT, Al-Khyat LS, Al-Masri DM, Jaradat NA (2004) A pilot study to investigate over-the-counter drug abuse and misuse in Palestine. Saudi Med J 25(12): 2029–2032 Wazaify M, Shields E, Hughes CM, McElnay JC (2005) Societal perspectives on over-the-counter (OTC) medicines. Fam Pract 22(2):170–176

Clinical Pharmacokinetics: ADME, Bioavailability and Bioequivalence, and Dosage Adjustments in CKD and Liver Disease

14

A. N. Nagappa and Shvetank Bhatt

Abstract

Applied clinical pharmacokinetic practice is the requirement of evidence-based medicine. Especially for inpatient whose condition is very serious, the practice of PK/PD is going to help in the recovery of the patients. In patients with impaired kidneys and liver functions, there is a need for dose adjustments to optimize the outcomes and avoid overdose of medicine. The calculations of PK/PD parameters and application of this knowledge are the scope of clinical pharmacist in the therapeutic team. Keywords

Bioavailability · Bioequivalence · Renal clearance · Hepatic clearance · Therapeutic drug monitoring

14.1

Clinical Pharmacokinetics: ADME

Pharmacokinetics and pharmacodynamics are two important aspects of drugs administered to the body. Pharmacokinetics is described as what the body does to a drug, while pharmacodynamics is defined as what a drug does to the body (Mehrotra et al. 2007). When a drug is administered by oral route, the drug has to undergo various steps and stages in the body as the drug being a foreign substance itself will be thrown out of the body depending upon its pharmacokinetic profile. Drug can be administered in various formulations through the different routes like oral sublingual, intramuscular, intravenous, subcutaneous, and topical. However, in A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_14

247

248

A. N. Nagappa and S. Bhatt

Fig. 14.1 Clinical pharmacokinetics

order to discuss pharmacokinetics, we chose oral administration through which the drug will go through all the major mechanisms of pharmacokinetics (Alagga and Gupta 2021; Jeong et al. 2020): absorption, distribution, metabolism, and excretion (Fig. 14.1) (Ohnishi et al. 2019). All these processes are followed during drug administration and happen simultaneously leading to elimination of the drug. Absorption is the first step in which the administered drug gets dissolved in the body forming body fluids to the blood vessels. Details on the principles of absorption shall be discussed further in this chapter. After the absorption of the drug from the blood vessels, it goes to the liver where it is subjected to metabolism by the liver enzymes (DeLeve 2003). The liver enzymes convert the administered drug into metabolites by phase one and phase two reactions. A fraction of administered drugs escapes the metabolic process and reaches into the systemic circulation. The appearance of parent drug in systemic circulation from the site of administration is known as “Absorption.” The drug from the blood reaches the tissues and cells by the process called “Distribution.”. (de Bruyn et al. 2021). The drug that goes to the kidney is subjected to excretion. Other routes of excretion of the drug include tears, saliva, and sweat. The excretion of the drug other than in urine is called as extrarenal excretion (Kok-Yong and Lawrence 2015). The drug bind to the receptors present on the cells and produces its effect, adverse effects etc. Generally the intensity of effect depends on how much drug enters into the systemic circulation and further to the tissues and cells. Conventional and nontargeted drug delivery is associated with greater risk of adverse effects. In this process, the development of targeted drug delivery system offers advantage and freedom from most of the adverse drug effects which are seen in a conventional

14

Clinical Pharmacokinetics: ADME, Bioavailability and Bioequivalence, and. . .

249

dosage form as the drug is reaching its targets of action in sufficient quantity to produce therapeutic effects (Tiwari et al. 2012). Further, the molecule concentration in the blood starts declining due to metabolism and excretion and secretion. This will continue and ends till the entire drug in the body is excreted in urine and skin. To understand the mechanism of drug ADME, one needs to describe the processes in terms of mathematics (McKenna et al. 2019). Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Clinical pharmacokinetics is the enhancement of efficacy and the reduction of toxicity of the drug. It is one of the objectives of clinical pharmacokinetics (Kang and Lee 2009). Plasma drug concentration is affected by the rate at which drug is administered, volume of distribution, and its clearance. In order to ensure continuous drug therapy, one should maintain blood concentration above the minimum effective concentration and should never allow drug concentration to cross the minimum toxic concentration. In order to maintain concentration within therapeutic window, one need to repeat the doses, whenever the concentration of the drug falls below minimum effective concentration. In this way, the concentration is maintained within the therapeutic window causing no harm to patient with high concentrations of the drug above minimum toxic concentration. It means the drug administered maximizes the therapeutic effectiveness without any major hazardous effects (Kang and Lee 2009; https://www.msdmanuals.com/en-in/professional/clinical-pharmacology/phar macokinetics/overview-of-pharmacokinetics). It is very necessary to do analysis of drug administered by taking the blood sample of the patient and measuring it. The measured value will give clue to administer next dose of the drug. The effectiveness of the drug is dependent on blood concentrations. It is always not possible to measure drug concentration of blood. However, drug concentrations are empirically administered so that the patient gets the drug in a continuous fashion. Most of the studies state that serum can also be used as an alternative process to evaluate the patient’s response and compute the doses regimen. It is important to understand the steady state concentrations or blood concentration do not follow simple linear Pharmacokinetics. In linear Pharmacokinetics, when doses are increased steady state concentration increase in a proportional fashion for most of the drugs. However, when steady-state concentration changes in an abrupt fashion after the doses are given, it is described as the drug follows nonlinear pharmacokinetics (Ahmed 2015). Steady-state concentrations increase more than acetated at higher dose. It is explained that the process of drug elimination (excretion) has become saturated. One can explain the mechanism of alterations in the steady-state concentration may be binding of the drug to plasma protein which is saturable plasma protein binding site (Wadhwa and Cascella 2021). In another way, some drugs induce auto-induction which increases its own rate of metabolism, for example, carbamazepine (Perucca 2006). It is very difficult to administer doses appropriately which show nonlinear pharmacokinetics. However, drugs which follow linear pharmacokinetics are more state forward and easy to administer in subsequent doses. In pharmacology, the volume of distribution is the theoretical volume that would be necessary to contain

250

A. N. Nagappa and S. Bhatt

the total amount of an administered drug at the same concentration that it is observed in the blood plasma. The concept of volume of distribution is hypothetical volume which assumes what should be the amount of volume for the drug administered in terms of concentration measured in blood plasma. The volume of distribution is an important pharmacokinetic parameter because it determines the loading doses. How the drug binds in the blood or serum compared to the binding in tissues is also an important determinant of the volume of distribution for a drug. A drug’s volume of distribution therefore reflects the extent to which it is present in extravascular tissues and not in the plasma (Mansoor and Mahabadi 2021). Example one, if a 5 g of a drug are added and distributed throughout a tank and the resulting concentration is 0.25 g per liter, calculate the volume of the tank. Now, V ¼ the amount of the drug in the tank divided by the concentration: 5=0:25 ¼ 20 L Example two, if 150 ml of the drug is administered intravenously and plasma concentration of the drug is determined to be 6 ml per liter, calculate the volume of distribution: 150=6 ¼ 25 L Example three, a physician wants to administer an antibiotic at a rate of 5 mg per hour by IV infusion. The drug is known to have drug elimination rate constant of 4 mg per hour, and the volume of the distribution (single compartment) is 12 L. What loading dose should be recommended if the drug label has to reach 5 μg/mL given: Infusion rate ¼ 5 mg/h Elimination rate ¼ 4 mg/h Volume of distribution ¼ 12 L Required concentration ¼ 5 μg/mL Loading dose ¼ volume of distribution Css 12000  5 ¼ 60000=1000 ¼ 60 mL Pharmacokinetic modeling consumes single compartment, two compartments, and multi-compartments (https://derangedphysiology.com/main/cicm-primaryexam/required-reading/pharmacokinetics/Chapter%202.0.1/single-and-multiplecompartment-models-drug-distribution). Compartmental models are classified by the number of compartments needed to describe the drug behavior in the body. The compartment does not represent specific tissue or fluid but represents a group of similar tissues or fluids, for example, lymph and blood. These models are used to predict the time course of drug concentration in the body (https:// derangedphysiology.com/main/cicm-primary-exam/required-reading/pharmacoki netics/Chapter%202.0.1/single-and-multiple-compartment-models-drug-distribu tion; Vendel et al. 2019). It is assumed that the drug under study is distributed

14

Clinical Pharmacokinetics: ADME, Bioavailability and Bioequivalence, and. . .

251

throughout the body into a single compartment. This model is appropriate for drugs with rapid ready distribution and reduces plasma and other body fluids (https:// accesspharmacy.mhmedical.com/content.aspx?bookid¼513§ionid¼41488021 ). A two-compartment model is suitable for drugs which equilibrate between the peripheral tissues. Two-compartment models are useful for the estimation of clearance and prediction of the appropriate doses. For many drugs, multi-compartment kinetics may be appropriate. One should appreciate here the difference between central distribution volumes which is important in deciding the dose strategy (Ahmed 2015). Clearance is the volume of serum or blood completely cleared of the drug for unit time. Clearance is the most important parameter by which one can determine the maintenance dose (Leung et al. 2016): Maintenance dose ¼ Clearance  Css In order to achieve theophylline serum concentration of 10 μg/mL in a patient with a clearance rate of 3L/h, one need to administer a maintenance dose of 30 mg/h. It should be known that the liver is responsible for drug metabolism and the kidney is responsible for drug elimination. Drug clearance for an organ is calculated by multiplying blood flow into the organ and the extraction ratio of the drug. Extraction ratio of the drug is the ability of an organ to remove or extract the drug from blood or plasma: ER ¼ ðCin  CountÞ=Cin The hepatic clearance is the product of liver blood flow and the hepatic extraction ratio (Pang et al. 2019): CLH ¼ LBF:CL’int The intrinsic ability of the liver enzyme to metabolize a drug is called haptic extraction ratio. Hepatic clearance is very sensitive to changes in the liver blood flow. Due to congestive heart failure or liver diseases, high hepatic extraction ratio (more than 70%) indicates the liver capacity to metabolize drug is very high and hepatic clearance is mainly a function of liver blood flow. Hepatic clearance does not change much when protein-binding displacement or enzyme induction or inhibition occurs due to drug interaction, for example, lidocaine, morphine, and tricyclic antidepressants. When the liver blood flow decreases due to liver or cardiac diseases, in such cases low hepatic extraction ratio (less than 30%) does not cause much changes, examples are valproic acid, phenytoin, and warfarin. Verapamil has a hepatic extraction ratio of 90% (ERH ¼ 0.90) for patients with normal blood flow (LBF ¼ 1.5 L/min). Calculate the haptic clearance (https:// pharmacy.ufl.edu/files/2013/01/2005-exam2-5128.pdf):

252

A. N. Nagappa and S. Bhatt

CLH ¼ LBF: ERH , CLH ¼ 1:5 L= min  0:90 ¼ 1:35 L= min , Hepatic clearance would be 1:35 L per min :

14.2

Renal Clearance

The renal clearance is physiologically predetermined by the glomerular filtration rate (GFR), the free faction of the drug in the blood or serum (fb), the renal tubular secretion (Clsec), and the fraction of the drug reabsorbed in the kidney (FR). The renal clearance of the drug is greater than the glomerular filtration rate. It is likely that the drug was eliminated in part by active tubular secretion (Grootaert et al. 2012).

14.3

Half-Life

Half-life is the time that it takes for serum concentration to decrease by 50% in the elimination phase which is constant. It is also called as T half (Fig. 14.2a and b) (https://www.sciencedirect.com/topics/medicine-and-dentistry/elimination-halflife). t½ ¼ 0:693=ke, Ke, elimination rate constant ¼ ‐ðIn C1  In C2Þ=ðt1  t2Þ

a

b Concentration (mg/L)

Concentration (mg/L)

10

t1/2 1

0.1

0

10

20

30

40

20 18 16 14 12 10 8 6 4 2 0

50

Time (h)

Fig. 14.2 (a and b) Graphical presentation of half-life

3 t1/2 0

10

20 30 Time (h)

5 t1/2 40

50

14

Clinical Pharmacokinetics: ADME, Bioavailability and Bioequivalence, and. . .

253

The half-life determines the time to steady-state concentration and the dosage interval. The half-life is dependent parameters because their values depend on the clearance (Cl) and volume of distribution (Vd).

14.4

Conclusion

The practices of pharmacokinetics and pharmacodynamics have become fundamental in critical clinical practice and research. PK/PD modeling is helpful in guiding the therapeutic team in taking appropriate actions in terms of dose, duration, and ADR management. These are highly valuable in patients with impaired kidneys and liver.

References Ahmed TA (2015) Pharmacokinetics of drugs following IV bolus, IV infusion, and oral administration, basic pharmacokinetic concepts and some clinical applications. IntechOpen, Rijeka Alagga AA, Gupta V (2021) Drug absorption. StatPearls, Treasure Island de Bruyn C, Kops MŠ, Mazzolari A, Kirchmair J (2021) GLORYx: prediction of the metabolites resulting from phase 1 and phase 2 biotransformations of xenobiotics. Chem Res Toxicol 34(2): 286–299 DeLeve LD (2003) Alterations in hepatic metabolism of drugs. In: Kufe DW, Pollock RE, Weichselbaum RR et al (eds) Holland-Frei cancer medicine, 6th edn. BC Decker, Hamilton Grootaert V, Willems L, Debaveye Y, Meyfroidt G, Spriet I (2012) Augmented renal clearance in the critically ill: how to assess kidney function. Ann Pharmacother 46(7–8):952–959 Jeong SH, Jang JH, Lee YB (2020) Pharmacokinetic comparison of three different administration routes for Topotecan hydrochloride in rats. Pharmaceuticals (Basel) 13(9):231 Kang JS, Lee MH (2009) Overview of therapeutic drug monitoring. Korean J Intern Med 24(1): 1–10 Kok-Yong S, Lawrence L (2015) In: Ahmed TA (ed) Drug distribution and drug elimination, basic pharmacokinetic concepts and some clinical applications. IntechOpen, Rijeka Leung L, Yang X, Strelevitz TJ, Montgomery J, Brown MF, Zientek MA, Banfield C, Gilbert AM, Thorarensen A, Dowty ME (2016) Clearance prediction of targeted covalent inhibitors by in vitro-in vivo extrapolation of hepatic and extrahepatic clearance mechanisms. Drug Metab Dispos 45(1):1–7. https://doi.org/10.1124/dmd.116.072983 Mansoor A, Mahabadi N (2021) Volume of distribution. StatPearls Publishing, Treasure Island McKenna MT, Weis JA, Quaranta V, Yankeelov TE (2019) Leveraging mathematical modeling to quantify pharmacokinetic and Pharmacodynamic pathways: equivalent dose metric. Front Physiol 10:616 Mehrotra N, Gupta M, Kovar A et al (2007) The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int J Impot Res 19:253–264 Ohnishi S, Fukumura K, Kubota R, Wajima T (2019 Sep) Absorption, distribution, metabolism, and excretion of radiolabeled naldemedine in healthy subjects. Xenobiotica 49(9):1044–1053 Pang KS, Han YR, Noh K, Lee PI, Rowland M (2019) Hepatic clearance concepts and misconceptions: why the well-stirred model is still used even though it is not physiologic reality? Biochem Pharmacol 169:113596

254

A. N. Nagappa and S. Bhatt

Perucca E (2006) Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 61(3):246–255 Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, Bannerjee SK (2012) Drug delivery systems: an updated review. Int J Pharmaceut Investig 2(1):2–11. https://doi.org/10. 4103/2230-973X.96920 Vendel E, Rottschäfer V, de Lange E (2019) The need for mathematical modelling of spatial drug distribution within the brain. Fluids Barriers CNS 16(1):12. https://doi.org/10.1186/s12987019-0133-x Wadhwa RR, Cascella M (2021) Steady state concentration. StatPearls Publishing, Treasure Island

Biotherapeutics: Monoclonal Antibodies, Biologicals, Biogenerics, Biosimilar, and Biobetters

15

A. N. Nagappa and Shvetank Bhatt

Abstract

Biopharmaceuticals had come into prominence following deciphering of human genome. A new branch known as biotherapeutics had revolutionized the therapeutics. New developments not only are scientific breakthrough but also provided novel drugs like monoclonal antibodies, vaccines, recombinant proteins, and gene therapy. Technology being sophisticated and being highly protected by patents, biotherapeutics are priced at very expensive levels. It is not affordable to everyone. However, many biotherapeutics after expiration of date of patents are made available as biogenerics, biosimilar, and biobetters. Keywords

Monoclonal antibodies · Biogenerics · Biosimilar · Biobetters · CAR-T therapeutics

15.1

Biotherapeutics

Biotherapeutics also known as biopharmaceutical or biologic is a pharmaceutical drug obtained from manufacturing/extracted from biological sources which are dissented from chemically synthesized drugs. Biopharmaceuticals include vaccines, blood components, allergenics, somatic cells, gene therapies, recombinant therapeutic proteins, and cell therapies (https://www.who.int/biologicals/vaccines/ biotherapeutic-products/en/; Kesik-Brodacka 2018).

A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_15

255

256

A. N. Nagappa and S. Bhatt

Biologics have emerged as new-generation therapeutics. They are considered as entirely different from chemically synthesized drugs, which are described as xenobiotic meaning these foreign entities are not part of the biological system (BlancoCastañeda et al. 2020). Biologics originated from living sources like humans, animals, plants, bacteria, fungi, and virus. The background of biological drugs is from innovation, and technologies are developed in the field of biotechnology which is having history of two to three decades. These innovations came into prominence as synthetic chemical-based drugs begin to show limitations of side effects, leading to safety concerns and failing to get regulatory approvals (Morrow and Felcone 2004; https://www.conserve-energy-future.com/biotechnology-types-examplesapplications.php). The decoding of human genome in 2000 led to the development of several key biotechnological innovations like PCR, CDNA, and hybridoma which promise availability of biological drugs in sufficient quantity for commercial applications (Hood and Rowen 2013). Biological drugs are engineered micromoles made up of proteins, nucleic acid, and also products like blood components and vaccine. Biological therapeutics also include gene therapy, somatic cell therapy, tissueengineered medicines, and combinations thereof. Programmed cell death 1 inhibitor, program death ligand inhibitor, chimeric antigen receptor, and T-cell therapy are the latest ones (Mabonga and Kappo 2019; Karpanen and Olweus 2015; National Research Council (US) Committee on Methods of Producing Monoclonal Antibodies 1999).

15.2

Classifications of Biologics

Major classes of biological drugs include those extracted from living organism, produced by recombinant DNA technology products, vaccines, and gene therapy (Khan et al. 2016).

15.3

Extracted from Living Organism

Biologics extracted from living system include bovine insulin and pituitary extract which are some of the oldest forms. Currently, important biologics obtained from living systems by extraction include the following (Morrow and Felcone 2004):

15.3.1 Whole Blood and Other Blood Components Whole blood and other blood components, like packed RBC, platelet concentrate, cryoprecipitate, and fresh frozen plasma, are a human blood from standard blood donation which is used to substitute blood in the treatment of massive bleeding and server anemia and for transfusion (Arya et al. 2011).

15

Biotherapeutics: Monoclonal Antibodies, Biologicals, Biogenerics,. . .

257

15.3.2 Organs and Tissue Transplantation Organ or tissue from a healthy donor is transplanted into a recipient who has a damaged or missing organ or tissue. Organs and/or tissues that are transplanted within the same person body are called autografts, for example, in coronary artery bypass surgery. Transplants that are performed between two subjects of the same species are called allografts. Organ transplanted by allograft surgery are the heart, kidney, liver, lungs, intestine, thymus, and pancreas. Tissue transplants include cornea, skin, heart valves, nerves, veins, tendons, and bones (Al-Bar and ChamsiPasha 2015; Madariaga et al. 2015).

15.4

Stem Cell Therapy

Stem cell therapy uses cells obtained from umbilical cord blood and also bone marrow transplant therapy (McKenna and Sheth 2011). The US FDA has approved five hematopoietic stem cell products derived from umbilical cord blood for the treatment of blood and neurological disease. Bone marrow therapy is used for the treatment of leukemia and lymphoma cancer therapy. Stem cell treatments are also available for neurodegenerative disease like Parkinsonism and conditions like diabetes and heart failure (Khaddour et al. 2021).

15.5

Antibodies for Passive Immunization

Immunization is nothing but vaccinations. Vaccines are of two types, i.e., boosting our active immunity and passive immunity. With this, the immune system is challenged by antigens which develop specific antibodies to fight the infection of the antigens injected. For example, Tetvac protests one from infection of tetanus. Tetvac contains antigens of tetanus causing bacteria whose virulence is nullified and antigenicity is retained. In the passive immunity, antibodies are injected to provide the immunity for already growing bacteria in the body, for example, antisnake venom. They are also used to treat a virus infection (Marcotte and Hammarström 2015).

15.6

Human Breast Milk

Human breast milk is a primary source of nutrition for the new born. The milk produced immediately after birth is called colostrum. It is a nutrient-rich fluid produced by female mammals immediately after giving birth, loaded with immune, growth, and tissue repair factors. Bovine colostrum, a raw material for immune milk preparations, can be used to treat or prevent infections of the gastrointestinal tract (Ballard and Morrow 2013).

258

15.7

A. N. Nagappa and S. Bhatt

Fecal Microbiota Transplant (FMT)

FMT is the transfer of fecal material that contains bacteria and natural antibacterial materials from healthy individuals to diseased persons. It is used in patients who have been infected with antibiotic-assistant bacteria, and it is also used to treat ulcerative colitis and other gastrointestinal conditions (Blanchaert et al. 2019).

15.8

Human Reproductive Cells

Human fertilization is the union of the human egg and sperm to make zygote or fertilized egg. Now technologies like in vitro fertilization which are test tube babies are offered for the couples who have difficulty in natural birth process (Wymelenberg, and Institute of Medicine (US). Science and Babies: Private Decisions, Public Dilemmas 1990).

15.9

Biotherapeutics Produced by Recombinant DNA

Before the advent of the recombinant DNA technology, one should use extracted proteins from dead animals. The recombinant DNA technology can produce human proteins or be used for therapeutic application. The proteins obtained from animal sources have serious drawback such as allergic hypersensitivity reactions in the recipients. Molecules like interferon, human insulin, and human growth hormone are available for treatment of disease. Monoclonal antibodies are also made by hybridoma technology. Using hybridoma technologies, monoclonal antibodies are produced. Moreover, they are used in the treatment of many diseases including orphan diseases, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and many cancers (Adrio and Demain 2010; Breschkin 1987; Wang et al. 2017) (Table 15.1).

15.10 Receptor or Constructs (Fusion Proteins) Receptor constructs, also called as fusion proteins based on naturally occurring receptor, link to the immune globulin frame. Biologics as a class of medications have a profound impact on many fields like rheumatology, oncology, hematology, cardiology, dermatology, gastroenterology, and neurology. The major kinds of biopharmaceutical include blood factors (factor 8 and factor 9), thrombolytic agents (tissue plasminogen activator), and hormones (insulin, glucagon, growth hormone, gonadotropins, hematopoietic growth factors, erythropoietin, colony-stimulating factors, interferons, interleukin, vaccines, monoclonal antibodies, tumor necrosis factor, therapeutic enzymes) (Tillmann et al. 2009).

15

Biotherapeutics: Monoclonal Antibodies, Biologicals, Biogenerics,. . .

259

Table 15.1 Examples of some biotherapeutics USAN/INN Abatacept

Trade name Orencia

Adalimumab

Humira

Alefacept

Amevive

Erythropoietin

Epogen

Etanercept

Enbrel

Infliximab

Remicade

Trastuzumab

Herceptin

Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn’s disease Chronic plaque psoriasis Anemia arising from cancer chemotherapy, chronic renal failure, etc. Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn’s disease Breast cancer

Ustekinumab

Stelara

Psoriasis

Denileukin Diftitox

Ontak

Cutaneous T-cell lymphoma (CTCL)

Golimumab

Simponi

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis

Indication Rheumatoid arthritis

Technology Immunoglobulin CTLA-4 fusion protein Monoclonal antibody

Immunoglobulin G1 fusion protein Recombinant protein

Recombinant human TNF-receptor fusion protein

Mechanism of action T-cell deactivation TNF antagonist

Incompletely characterized Stimulation of red blood cell production TNF antagonist

Monoclonal antibody

TNF antagonist

Humanized monoclonal antibody Humanized monoclonal antibody Diphtheria toxin engineered protein combining interleukin-2 and diphtheria toxin Monoclonal antibody

HER2/neu (erbB2) antagonist IL-12 and IL-23 antagonist Interleukin2 receptor binder

TNF antagonist

15.11 Vaccines Vaccines provide active acquired immunity to a particular disease. Vaccines contain disease-causing microorganism which is either killed or weakened. It may be bacterial toxin or one of its surface proteins. Vaccines stimulate the body’s immune

260

A. N. Nagappa and S. Bhatt

system to recognize the bacteria and destroy it. They are active which can prevent future infection (Clem 2011).

15.12 Viral Gene Therapy Viral gene therapy is a delivery of nucleic acid into patient’s cells to treat a disease. Some of the gene therapy which is successful includes bone marrow transplantation and organ transplantation in which foreign DNA are introduced into a patient (Lundstrom 2018).

15.13 Biosimilar Many biological drugs and monoclonal antibodies are developed and registered as patents. They are very expensive although they are very effective with acceptable safety and efficacy norms. Once the patent expires, the molecule is available for manufacture and use. The price of the patented medicine is very high and has limited market accessibility. Of the patented medicines, biological drugs are an opportunity for other manufacturers to produce biosimilar. Biosimilar is a generic version of patented brand biologic; however, we cannot compare the generic medicine of chemical drugs. Biological drugs have a huge molecular structure. Biological structures and biological activities of biological drugs are unpredictable as in the case of chemically synthesized drugs. Biological drug activities have to be established in terms of biological units of activity instead of chemical structure. Biosimilar, when introduced, are likely to provide competition brand biology and bring down the price of the brand medicine (Misra 2012).

15.14 Biobetters Biobetters are medicines that are generic versions of the brand products which are pronounced safe and effective than the brand biodrugs (Sharma et al. 2019).

15.15 Conclusion The beginning of biotherapeutics had advanced the treatment of disease to the next level. The drawback of side effects of majority of chemistry-based drugs is addressed by new biological drugs. All most all human proteins are made available for use in treatment without fear of adverse immunogenic reactions. There are many breakthrough medicines that are developed by new technologies.

15

Biotherapeutics: Monoclonal Antibodies, Biologicals, Biogenerics,. . .

261

References Adrio JL, Demain AL (2010) Recombinant organisms for production of industrial products. Bioeng Bugs 1(2):116–131 Al-Bar MA, Chamsi-Pasha H (2015) Organ transplantation. In: Contemporary bioethics: islamic perspective. Springer, Cham Arya RC, Wander G, Gupta P (2011) Blood component therapy: which, when and how much. J Anaesthesiol Clin Pharmacol 27(2):278–284 Ballard O, Morrow AL (2013) Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am 60(1):49–74. https://doi.org/10.1016/j.pcl.2012.10.002 Blanchaert C, Strubbe B, Peeters H (2019) Fecal microbiota transplantation in ulcerative colitis. Acta Gastroenterol Belg 82(4):519–528 Blanco-Castañeda R, Galaviz-Hernández C, Souto PCS, Lima VV, Giachini FR, Escudero C, Damiano AE, Barragán-Zúñiga LJ, Martínez-Aguilar G, Sosa-Macías M (2020 Mar) The role of xenobiotic-metabolizing enzymes in the placenta: a growing research field. Expert Rev Clin Pharmacol 13(3):247–263 Breschkin A (1987) Control of therapeutic goods produced by recombinant DNA technology. Dev Biol Stand 67:207–211 Clem AS (2011) Fundamentals of vaccine immunology. J Glob Infect 3(1):73–78. https://doi.org/ 10.4103/0974-777X.77299 Hood L, Rowen L (2013) The human genome project: big science transforms biology and medicine. Genome Med 5(9):79 Karpanen T, Olweus J (2015) T-cell receptor gene therapy—ready to go viral? Mol Oncol 9(10): 2019–2042 Kesik-Brodacka M (2018) Progress in biopharmaceutical development. Biotechnol Appl Biochem 65(3):306–322 Khaddour K, Hana CK, Mewawalla P (2021) Hematopoietic stem cell transplantation. StatPearls Publishing, Treasure Island Khan S, Ullah MW, Siddique R, Nabi G, Manan S, Yousaf M, Hou H (2016) Role of recombinant DNA technology to improve life. Int J Genomics 2016:2405954 Lundstrom K (2018) Viral vectors in gene therapy. Diseases 6(2):42 Mabonga L, Kappo AP (2019) Protein-protein interaction modulators: advances, successes and remaining challenges. Biophys Rev 11(4):559–581 Madariaga ML, Kreisel D, Madsen JC (2015) Organ-specific differences in achieving tolerance. Curr Opin Organ Transplant 20(4):392–399. https://doi.org/10.1097/MOT.0000000000000206 Marcotte H, Hammarström L (2015) Passive immunization: toward magic bullets. Mucosal Immunol 2015:1403–1434. https://doi.org/10.1016/B978-0-12-415847-4.00071-9 McKenna D, Sheth J (2011) Umbilical cord blood: current status & promise for the future. Indian J Med Res 134(3):261–269 Misra M (2012) Biosimilars: current perspectives and future implications. Indian J Pharm 44(1): 12–14 Morrow T, Felcone LH (2004) Defining the difference: what makes biologics unique. Biotechnol Healthc 1(4):24–29 National Research Council (US) Committee on Methods of Producing Monoclonal Antibodies (1999) Generation of hybridomas: permanent cell lines secreting monoclonal antibodies. In: Monoclonal antibody production. National Academies Press, Washington

262

A. N. Nagappa and S. Bhatt

Sharma A, Kumar N, Kuppermann BD et al (2019) Biologics, biosimilars, and biobetters: different terms or different drugs? Eye 33:1032–1034 Tillmann HL, Patel K, McHutchison JG (2009 Feb) Role of growth factors and thrombopoietic agents in the treatment of chronic hepatitis C. Curr Gastroenterol Rep 11(1):5–14. https://doi. org/10.1007/s11894-009-0002-x Wang X, Yang L, Huang F, Zhang Q, Liu S, Ma L, You Z (2017) Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunol Lett 184:7–14 Wymelenberg S, Institute of Medicine (US). Science and Babies: Private Decisions, Public Dilemmas (1990) New technologies: the ethical and social issues. National Academies Press, Washington

Introduction to Clinical Trials and Biostatistics

16

A. N. Nagappa and Shvetank Bhatt

Abstract

Clinical research (CR) and clinical trials (CTs) are basis of new drug development for submission to regulatory bodies for approval. Despite careful consideration of most factors to avoid bias and errors in results of CTs, one is not sure of the correctness of results. Application of biostatistics (Biost) is essential for predicting the safety and efficacy of new drugs. This is why pharmacovigilance (PV) is indicated for all the drugs approved for clinical use by the regulatory authorities. Biological variations among human beings (HBs) are the major reason for insistence of CTs and PV in pharmaceutical drug developments. Keywords

Biostatistics · Clinical trials · Pharmacovigilance · Institutional review board · Informed consent form

16.1

Clinical Trials

Medicines are essential for disease management and maintenance of health, for example, many people are having hypertension (HTN), and HTN, if not managed or controlled within the physiological limits, damages vital organs like the kidney and heart and also may lead to stroke causing medical emergency and death. Hence, it is essential to monitor and control blood pressures by lifestyle modification and through taking antihypertensive drugs. Although lifestyle modification can bring HTN effectively without causing any adverse effects, patients prefer to use A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_16

263

264

A. N. Nagappa and S. Bhatt

medication and control the blood pressure. HTN is sustained due to various pathophysiology changes (Oparil et al. 2018). All medicines licensed for management of HTN have their own list of adverse reactions; hence, the search for a better molecule and better drug is a never-ending undertaking. For example, angiotensin-converting enzyme inhibitors like lisinopril and ramipril cause dry cough which was found to be due to enhanced levels of bradykinin. Bradykinin is also metabolized by ACE when ACE inhibitors are used in the management of HTN. Bradykinin accumulates and causes dry cough. Dry cough was the serious limitations for using ACE inhibitor in the management of HTN. In order to overcome the effect of angiotensin causing HTN, it becomes necessary to discover a drug which is capable of preventing HTN and bradykinin. The research indicated that angiotensin 2 peptide caused HTN by binding angiotensin to receptors present in the intima of blood vessels. This led to the discovery of angiotensin receptor blockers like losartan and candesartan which do not cause dry cough (Jancso et al. 2004; Unger 2001). The above example established the need for research and development (R&D) activity to find out new molecules to overcome the limitations of existing drugs. In this hope, drug discovery is very much active in all fields of therapeutic category. The first challenge after inventing a new drug is to understand how the drug is going to act in HBs. Several in vitro and preclinical studies (PCS) have to be performed in order to get a clue regarding the possibility of development of drugs for a clinical use. Studies of new drugs in HB are called clinical studies (CSs). CSs are carried out in human beings to establish efficacy and safety of the new drug. The new drug being xenobiotic is totally unpredictable. It may cause beneficial effects or may cause severe adverse reactions. In order to understand the nature of drug action in HBs, one has to take at most care while studying the effects of new drug (Polson and Fuji 2012). When the drug is administered for the first time to humans at most care and precaution with facilities to protect the human subject (sub) who have volunteered him/her in the interest of drug development to be used for future patients. Here, small numbers of volunteers are used to assess the safety and efficacy of the drug in HBs. In case of any drug adverse reactions, all facilities to protect the volunteer from injury and death are kept ready. The clinical development of the drug is done in sequence of phases (PHs). They are PH-1, PH-2, PH-3, and PH-4. Each PH have unique objective which established the safety and efficacy of the medicine in clinical use. It is also interesting to know as we move from PH-1 to PH-4. More and more, HBs are tested for the drug effect and the point of safety and efficacy. CTs are defined as scientific investigations in human sub which examines and evaluates safety and efficacy of drugs and therapies. Three important concepts of CTs are experimental unit, treatment, and evaluation of the treatment. The experimental unit is usually referred to as a sub from targeted population under study. The experimental unit is usually used to specify the intended study population in which result of the study are concluded. For example, the intended population could be patients with certain diseases at certain stages or

16

Introduction to Clinical Trials and Biostatistics

265

healthy human sub (https://www.cancer.org/treatment/treatments-and-side-effects/ clinical-trials/what-you-need-to-know/phases-of-clinical-trials.html).

16.2

Treatment

In a CT, treatment can be a placebo or any new drug diet surgery, diagnostic, medical device, or health education program. It may also have no treatment. Other examples may include surgical removal, radio therapy, and chemotherapy as a combination of surgery and chemotherapy. For example, in the treatment of breast cancer, a combination of surgery, chemotherapy, and radiation therapy may be used. Treatment also means the use of MRI with a radio contrasting agent as a combination of diagnostic test or may be an agent for enhancement of drug effect and diagnostic test. Evaluation means traditional evaluation of safety and efficacy along with designed evaluations to assess quality-of-life pharmacogenomics and pharmacoeconomics. Pharmacoeconomic evaluations comprise of costeffectiveness of the study, cost-benefit analysis, and cost minimization analysis. The scope for the CT should not be limited to clinical effectiveness and safety but should also include quality-of-life studies, impact of genetic factors, pharmacoeconomics, and outcome research associated with the treatment (Dervieux and Bala 2006).

16.3

Protection of Human Sub in CTs

It is very important to protect and safeguard the participants of CTs. The history of CTs is full of misdeeds and exploitations of participants of human volunteers. It is the duty of the sponsor (SPON) and CT staff to take care and ensure the safety and quality of life of the sub participating in CT. The SPON who invest in the CTs for the sake of business is likely to vary. During the CTs, subs are supposed to sign a contract in which the benefits of participating in CTs are explained in detail. Sub should be aware regarding the risk involved in participating in CT. Subs who have understood the risk and benefit of the investigational drug should agree with the informed consent form. It is also important to take a written agreement by the SPON regarding compensation, and in case any sub gets seriously ill during the CT, he/she should be paid complete medical expenditure. Overall patient’s rights to be protected from exploitation. The approved protocol by the IRB should be followed without any amendments regarding the human protection and welfare (https://clinicaltrials.gov/ProvidedDocs/99/NCT03460899/Prot_SAP_000.pdf).

266

16.4

A. N. Nagappa and S. Bhatt

Financial Disclosure by Clinical Investigators (INVs)

SPON is required to maintain the accounts of expenses and projected view of the source of investments. The accounting system should be available for verification by the regulatory agencies in monitoring sub’s health. SPON should disclose finances to be used in the conduct of CT. SPON should not invest black money or illegal money for the conduct of CTs (https://ichgcp.net/5-sponsor) (Fig. 16.1).

16.5

Institutional Review Board (IRB)

An IRB, also known as an independent ethics committee, ethical review board, or research ethics board, is a type of committee that applies research ethics by reviewing the methods proposed for research to ensure that they are ethical. In CTs, a sub is defined as an individual who is observed or experimented with by an INV; an INV is a qualified individual who conducts research. It is very essential that in medical and related research using HBs as sub the IRB must necessarily ensure that the purpose of such research is directed toward the enhancement of knowledge regarding the human condition in relating to social and natural environment. The research on HB should be conducted under the condition no person or person becomes a mere instrument for the betterment of other HBs. The sub participating in any medical or scientific research should be dealt with dignity and respect with assurance of being looked after very well during CT. In case the subs get injured and

Fig. 16.1 Clinical product development phases

16

Introduction to Clinical Trials and Biostatistics

267

become handicapped, they should be rewarded with good compensation so that they can be secured financially (Kim 2012). The evaluation of protocol should be carried out precisely at all stages of the proposal – starting from research design experimentation, declaration of results, and the use of the results. Every evaluation shall bear in mind that the object of the trial are achieved, the data generated is told in a scientific manner and be useful for verification and retriever whenever required. Evaluation is aimed at the potential uses and abuses of the experiment and its results.

16.6

Good Laboratory Practices

CTs are to be conducted only after it gets approval by an authorized person who checks the necessity of the project and states whether the CT’s purpose is useful or harmful for the society. He/she also checks the essentiality of the project from an a external body. It is also very important to educate the participant of CT as sub regarding the project and its benefits along with the risk factor involved. If any volunteer feels that he/she is at life risk, he/she is permitted to withdraw from CT. There should not be any legal action against his/her withdrawal in the middle of investigations (https://globalhealthtrainingcentre.tghn.org/articles/understandingprinciples-good-clinical-laboratory-practices-gclp/). In CTs wherein a community or group of sub are involved, in order to encourage the sub to join, CT principles of voluntariness shall be adopted. Participants in CT are usually paid some amount for engaging in research or experiments on their own body. The payment should be the same for every individual and should not discriminate based on general economic social, literacy, and educational status. The participant of the CT should be aware of all the dangers associated with the drugs or experiments they are engaged in. In case any of the sub suffers from side effect or toxic effect, he/she should be treated and rehabilitated at the earliest (https:// globalhealthtrainingcentre.tghn.org/articles/understanding-principles-good-clinicallaboratory-practices-gclp/). Principles of privacy and confidentiality are the important parts of CTs. The sub should be assured no where their name, health conditions, diseases they suffer from, or medicines they are using should not be disclosed to anybody unless a court demands for judicial process. The identity of the sub is kept confidential and in case of any valid scientific and legal reasons should not be disclosed. It is also necessary to take the written permission from the sub to disclose the information. Principles of precaution and risk minimization command during all stages of research even after research the sub should not be harmed by any adverse effects (https://globalhealthtrainingcentre.tghn.org/articles/understanding-principles-goodclinical-laboratory-practices-gclp/). CT staff should be able to foresee the possible adverse drug events and be ready to give protection and medical add in case of any adverse events (AEs). The CT staff should be careful so that sub should bear the minimal risk due to drug administration (Sil and Das 2017). The principle of accountability and transparency states that the

268

A. N. Nagappa and S. Bhatt

research/experiments should be conducted in a fair, honest, impartial, and crystal clear manner. This is very important to see that there should not be any conflicts arising due to misinformation or lack of information. The research data of CT should be reserved for a prescribed period of time as agreed upon in ethics committeeapproved protocol. The research outcome is a precise data which should be used irrespective of social and economic status. This is known as principle of maximization of the public interest and of distributing justice. Principle of institutional arrangements states that all persons concerned to research should ensure that the planning of executing of procedures can be followed without any hindrance. All necessary arrangements should have been made in a bona fide and transparent manner so that CTs or research have credential of faith and trust. The principle of public domain is concerned with results emerging from research or experiments that should be brought to the notice of public domain and should generally made known through scientific publication and conference proceedings (Institute of Medicine (US) Committee on Regional Health Data Networks et al. 1994). The principle of compliance is about the persons who are conducting research or CT. They are also people or associates who are connected to such project involving CR through scientific and other publications. Principle of compliance states that persons who are conducting or associated with the research project involving human sub should ensure cent percent compliance with the guidelines and no way violate any of the principles discussed above (https:// clinicaltrials.gov/ProvidedDocs/99/NCT03460899/Prot_SAP_000.pdf).

16.7

Ethics Committee and Review of Protocol Approvals

Human ethics committee is also called institutional ethics committee (IRB). The IRB is an administrative body established to protect the rights and welfare of human research sub recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated to regulatory bodies (https:// www.pharmpress.com/files/docs/Principles_ClinPract_sample.pdf). Constitution of IRB comprises of the following position and their role and responsibility:

16.7.1 Constitution of IRB 1. The IRB should consist at least seven members who collectively have the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial, viz. (https://ichgcp.net/3-institutional-reviewboardindependent-ethics-committee-irbiec): (a) Chairperson – appointed (who is from outside the institution) (b) 1–2 basic medical scientists (c) 1–2 clinicians from various institutes (d) One legal expert or retired judge

16

Introduction to Clinical Trials and Biostatistics

(e) (f) (g) (h)

269

One social scientist One philosopher or ethicist One layperson from community Member secretary – appointed • For reviewing and making decision on each protocol, there should be at least five members with the following representations to meet the condition of the quorum: – Basic medical scientists (preferably one pharmacologist) – Clinicians – Legal expert – Social scientist/representative of nongovernmental voluntary agency/ philosopher/ethicist/theologian or a similar person – Layperson from the community • In any case, the IRB must include: – At least one member whose primary area of interest/specialization is nonscientific. – At least one member who is independent of the institution/trial site. • Besides, there should be appropriate gender representation on the IRB • If required, sub experts may be invited to offer their views • Further, based on the requirement of research area, e.g. AIDS, genetic disorders etc. specific patient groups may also be represented in the IBR (https://ichgcp.net/3-institutional-review-boardindependent-ethics-com mittee-irbiec)

16.7.2 Functions and Operations of IRB • Only those IRB members who are independent of the CT and the SPON of the trial should vote/provide opinion in matters related to the study. • Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or advise. • The IRB should perform its functions according to written standard operating procedures, should maintain written records of its activities and minutes of its meetings, and should comply with GCP and with the applicable regulatory requirement (s) (http://www.bvs.hn/Honduras/CEIB/The.Purpose.Composition. and.Function.of.an.IRB.pdf). • The INV may provide information on any aspect of the trial, but should not participate in the deliberations of the IRB or in the vote/opinion of the IRB. • The IRB should establish, document in writing, and follow its procedures, which should include: – Determining its composition (names and qualifications of the members) – Scheduling, notifying its members of, and conducting its meetings – Conducting initial and continuing review of trials – Determining the frequency of continuing review, as appropriate

270

A. N. Nagappa and S. Bhatt

– Specifying that no sub should be admitted to a trial before the IRB issues its written approval/favorable opinion of the trial – Specifying that no deviations from, or changes of, the protocol should be initiated without prior written IRB approval /favorable opinion of an appropriate amendment, except when necessary to eliminate immediate hazards to the sub or when the change(s) involves only logistical or administrative aspects of the trial – Specifying that the INV should promptly report to the IRB – Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial sub – Changes increasing the risk to sub and/or affecting significantly the conduct of the trial – All adverse drug reactions (ADRs) that are both serious and unexpected – New information that may affect adversely the safety of the sub or the conduct of the trial – Ensuring that the IRB promptly notify in writing the INV institution concerning – Its trial-related decisions/opinions, t – The reasons for its decisions/opinions, and – Procedures for appeal of its decisions/opinions (http://www.bvs.hn/Honduras/ CEIB/The.Purpose.Composition.and.Function.of.an.IRB.pdf)

16.7.3 Responsibilities of IRB • An IRB should safeguard the rights, safety, and well-being of all trial sub. • The IRB should obtain the following documents: – Trial protocol(s)/amendment(s) – Written informed consent form(s) – Sub recruitment procedures (e.g.,: aAdvertise) – Written information to be provided to sub – INV’s bBrochure (IB) – Available safety information – Information about payments and compensation – INV’s current curriculum vitae • Any other may need to fulfill its responsibilities

16

Introduction to Clinical Trials and Biostatistics

271

16.7.4 Responsibilities of IRB • The IRB should review a proposed CT within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: – Approval/favourable opinion – Mmodifications required prior to its approval/favourable opinion – Disapproval/negative opinion – Termination/suspension of any prior approval/favourable opinion • The IRB should consider the qualifications of the INV for the proposed trial, as documented by a current curriculum vitae and/or by any other relevant documentation the IRB requests. • The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human sub, but at least once per year. • The IRB may request more information than is given to study sub when, in the judgment of the IRB, the additional information would add meaning to the protection of the rights, safety, and/or well-being of the sub. • The IRB should review both the amount and the method of payment to sub to assure neither compulsion nor undue influence on the trial sub. • Payments to a sub should be prorated (day basis) and not wholly contingent on completion of the trial by the sub. • The IRB should ensure that information regarding payment to sub, including the methods, amounts, and schedule of payment to trial sub, is set forth in the written informed consent form and any other written information to be provided to sub (https://www.uab.edu/policies/content/Pages/UAB-RA-POL-0000122.html).

16.7.5 IRB/IEC • • • • • • •

US FDA: Use the term IRB. EMEA: Use the term IEC. ICH-GCP: Use the term IRB/IEC. Canada: Use the term REC (research ethics committee). IRB stands for “Institutional Review Board.” IEC stands for “Independent Ethics Committee.” IEC are generally established in regional or even national level – can review protocol from anyone. • IRB are generally established by an organization – will review protocols of that institution/organization. • Indian guidelines were developed mostly based on ICH-GCP guidelines (https:// globalresearchonline.net/journalcontents/v63-2/03.pdf).

272

A. N. Nagappa and S. Bhatt

16.7.6 Informed Consent Form • A major component of GCP is the method by which the researchers will obtain voluntary and informed consent from sub. • Informed consent is a process, not just a form. • Information must be presented to enable persons to voluntarily decide whether or not to participate as a research sub. • The procedures used in obtaining informed consent should be designed to educate the sub population in terms that they can understand. • In seeking informed consent, the following information should be provided to the sub: – Statement that the study involves research and explanation of the purpose of the research. – Expected duration of the sub’'s participation. – Description of the procedures to be followed, including all invasive procedures. and – Description of any reasonably foreseeable risks or discomforts to the sub. – Description of any benefits to the sub or others reasonably expected from research. If no benefit is expected, the sub should be made aware of this. – Disclosure of specific appropriate alternative procedures or therapies available to the sub – Statement describing the extent to which confidentiality of records identifying the sub will be maintained and who will have access to sub’'s medical records – Trial treatment schedule(s) and the probability for random assignment to each treatment (for randomized trials) – Compensation and/or treatment(s) available to the sub in the event of a trialrelated injury – An explanation about whom to contact for trial- related queries, rights of sub, and in the event of any injury – The anticipated prorated payment, if any, to the sub for participating in the trial – Sub’s responsibilities on participation in the trial – Statement that participation is voluntary, that the sub can withdraw from the study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the sub is otherwise entitled – Any other relevant statistics which may be required, viz.: 1. Any forcible situation under which sub participation in the study can be terminated by the INV 2. Any additional cost to the sub 3. The consequences of the withdrawal of sub from the study 4. Statement that the sub’s representative will be notified in a timely manner if predominant new results develop during the course of the study which may affect the willingness of the sub to continue participation

16

Introduction to Clinical Trials and Biostatistics

273

5. A statement that the particular treatment or procedure may involve risks to the sub (or to the embryo or fetus, if the sub is or may become pregnant), which are currently unforeseeable 6. Approximate number of sub enrolled in the study

16.7.7 Format of Informed Consent Form • Informed Consent Form to Participate in a CT Title of the study: Number assigned for the study: Initials of the sub: _____________ Name of the sub:______________ Birth date or age of the sub: _________________ Please initial box (sub)

16.7.8 Format of Informed Consent Form 16.7.9 Place Initial in Boxes 1. I am above 18 years old [ ]. 2. I confirm that I have read and understood the information sheet dated ___ for the above study and have had the opportunity to ask questions [ ]. 3. I understand that my participation in the study is voluntary and that I am free to withdraw at any time, without giving any reason, without my medical care or legal rights being affected [ ]. 4. I agree not to restrict the use of any data or results that arise from this study provided such a use is only for scientific purpose(s) [ ]. 5. I agree to take part in the above study.

274

A. N. Nagappa and S. Bhatt

Signature (or Thumb impression) of the sub/Legally Acceptable Representative: ____________________ Date:__/__/__

Signatory's Name: ____________

Signature of the INV:_______ Date: __/__/__ Study INV's Name:_______________ Signature of the Witness________ Date:__ /__ /__ Name of the Witness:_______________________

16.8

Protocol Contents

16.8.1 Title Page (a) (b) (c) (d) (e) (f)

Full title of the human study Protocol/study number and protocol version number with date The IND name/number of the investigational drug/drug name Comprehensive name and address of the SPON and CRO if any/INV List of INVs with complete affiliation Name of the facilities including clinical laboratories participated in the study

16.8.2 Table of Contents A Complete “Table of Contents” with All Appendices 1. Background and Introduction: (a) In vitro and in vivo preclinical experience (b) Human trial experience 2. Rationale of the study 3. Primary and secondary objectives of the study 4. Design of the study, i.e., blinding, sub number, site, study period, etc. 5. Population of the study 6. Eligibility of sub and their criteria for inclusion and exclusion 7. Assessment of studies including procedures and methods • Medical history, physical assessment types, testing of blood and urine, ECG, PFT, measurement of symptoms, dispensation and retrieval of medication, cohort assignment of sub, review of AE, etc. • Every visit should be described separately and number should be given. • Discontinued sub should be described in proper format and recorded. • Explain the procedure of handling of protocol waivers, if any.

16

8.

9. 10.

11.

12.

13.

Introduction to Clinical Trials and Biostatistics

275

• Criteria for sub with specific waiver should be described properly. • Explain the violation of protocol and how noncompliance will be treated. Study treatment (a) Dosing scheme or schedule (b) Study drug supplies and administration (c) Modification of dose for toxicity study (d) Possible interaction of drugs used in the study (e) Parallel therapy (f) Blinding procedures (g) Unbinding procedures Description of reporting of AEs and procedure to evaluate the events Summary of ethical consideration required in the study (a) Assessment of risk and benefits (b) Review of IRB and related communications (c) Process of information consent (d) Confidentiality statement of the sub going to participate in the study Monitoring of study and its supervision • Explanation of monitoring policies of study along with the details of person going to monitor with numbers of visits required per site • Completion requirement of case record form (CRF) • Study file from the INV along with the details that what is required to be stored after the study completion Management of investigational product (a) Give the description and packaging information of investigational product/ placebo (b) Required dose for the study (exact dose) (c) Process of packaging, labeling, and blinding of substances used in the study (d) Procedure of allocating treatment to the sub and identification code numbering system (e) Condition of storage for the substances used in the study (f) Accountability of the investigational product used in the study (g) Frame of methods and policy for management of leftover investigational products Data analysis • Details of the statistical method to be utilized including the size of the sample considered for the study • Effectiveness of primary as well as secondary end points • Safety end points • Statistical method applied to find out the level of significance • Methods used for obtaining the missing data • Sub with noncompliance • Withdrawal of sub, rationale, and circumstances for interim analysis, in case interim analysis is planned • Statistical considerations to evaluate the pharmacokinetics (PK) data, if applicable

276

A. N. Nagappa and S. Bhatt

14. Undertaking submitted by the INV As suggested as per the guidelines of regulatory authority

16.9

Appendices

• Synopsis of the particular study • Copies of consent form from the patient with complete patient information sheet • CRF and other data collection forms Summary of associated preclinical information of safety as well as any other documents referenced in the clinical protocol (Manti and Licari 2018)

16.10 Biostatistics (Biost) Biost is the process and approach applied to the collection, analysis, and interpretation of data of biological origin and specifically data-related biology of human health and medicine. Biost involves the analysis of human biology. It includes both health and disease states. While statistics includes all kind of statistics, Biost is used in CTs which are very important in drug development and discovery. Biost is a novel field that encompasses the designs, analysis, and interpretation of data for research in the field of public health and medicine. Experts of Biost arrive at assumptions about disease and health risks by evaluating and applying various formulas of mathematics and statistics to find out the actual impact of particular factor on health. Biost is important in discovering treatment approaches by the use of potential newer class of drugs for diseases like cancer. Biostatisticians help in designing, managing, and analyzing CTs of diseases including cancer. They also help to identify the causes and characteristics of cancer (Berger and Matthews 2006).

16.11 Conclusion Drug discovery and development have become highly expensive and cryptic and time-consuming. The in vitro, preclinical, PH-1, PH-2, and PH-3 human studies following PV are the distinct stages of drug discovery and development. The randomized clinical trials (RCT) are considered as gold standard of evidence for effectiveness of treatment and safety of a new drug. Due to unpredictability of drug reactions, extensive application for Biost is in practice. After learning the long-term effects of drugs, the PV is practiced very seriously.

16

Introduction to Clinical Trials and Biostatistics

277

References Berger VW, Matthews JR (2006) What does biostatistics mean to us. Mens Sana Monogr 4(1): 89–103 Dervieux T, Bala MV (2006) Overview of the pharmacoeconomics of pharmacogenetics. Pharmacogenomics 7(8):1175–1184 Institute of Medicine (US) Committee on Regional Health Data Networks, Donaldson MS, Lohr KN (1994) Confidentiality and privacy of personal data. In: Health data in the information age: use, disclosure, and privacy. National Academies Press, Washington Jancso G, Jaberansari M, Gasz B, Szanto Z, Cserepes B, Röth E (2004) Bradykinin and angiotensinconverting enzyme inhibition in cardioprotection. Exp Clin Cardiol 9(1):21–25 Kim WO (2012) Institutional review board (IRB) and ethical issues in clinical research. Korean J Anesthesiol 62(1):3–12 Manti S, Licari A (2018) How to obtain informed consent for research. Breathe (Sheff) 14(2): 145–152 Oparil S, Acelajado MC, Bakris GL et al (2018) Hypertension. Nat Rev Dis Primers 4:18014 Polson AG, Fuji RN (2012) The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients. Br J Pharmacol 166(5):1600–1602 Sil A, Das NK (2017) Ethics of safety reporting of a clinical trial. Indian J Dermatol 62(4):387–391 Unger T (2001) Pharmacology of AT1-receptor blockers. Blood Press 3:5–10

Introduction to Personalized Medicine and Pharmacogenomics

17

A. N. Nagappa and Shvetank Bhatt

Abstract

The research has indicated that all individuals respond differently to every medicine used. This variation arises due to genetic makeup of individual. Now it is possible to find out which individual reacts differently to PK/PD prescription. The new technology being offered is known as personalized medicine. The application of pharmacogenomics and allied technologies is utilized for the personalized medicine. Some drugs being extremely expensive or toxic in the personalized medicine is helpful in rationalizing the drug therapy. Keywords

Pharmacogenomics · Genetic polymorphisms · Personalized medicine

17.1

Precision Medicine

Recent discovery has clearly indicated that all of us react differently to the administered drugs. Individually all of us show different degree of response. It is to say that the dose requirement of everyone is different. The reason for this difference is individual’s genetic makeup (Vogenberg et al. 2010). Hence, it is now becoming important to study the genetic profile and find out how the patient is likely responding to the drug due to genetic factors. It is observed in clinical practice the wide variation in patient reaction to therapeutics. Personalized medicine can be considered as an extension of medical practice, wherein physicians try to optimize the dose for an individual patient based on his or her genetic makeup in A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_17

279

280

A. N. Nagappa and S. Bhatt

Fig. 17.1 Personalized medicines

order to reduce the side effects and improve the efficacy of the treatments (Cutter and Liu 2012). Facilities for diagnosis of individual patients’ response for treatment are available and are used to find whether a patient is responsive to what extent. Physician can adjust as per the requirement (Institute of Medicine (US) Committee on Assuring the Health of the Public in the 21st Century 2002). Personalized medicine is like tailoring of medical treatment after considering the individual genetic profile (Fig. 17.1). Personalized medicine draws and develops on inputs from scientific characteristics of a patient (Godman et al. 2013). The advances in genetics are continuously adding new information regarding genetic profile of individual patients. Doctors can distinguish the individual patient molecular profile and minimize the adverse effects for a drug. It can be also useful in saving money of the patients and other stakeholders by conducting pharmacoeconomic and outcome research. Personalized medicine has the potential to change the therapeutics and identify whether a particular patient is responsive for a particular drug or a new drug is required (Agyeman and Ofori-Asenso 2015). Personalized medicine is impacting patient care in many diseases. In breast cancer, it was observed that 15–30% of patients have an overexpression of HER2 (Iqbal and Iqbal 2014). We are required to identify whether the patient under treatment is belonging to overexpression category or not. Overexpression of HER2 makes them resistant for standard anticancer therapy. However, their response rate was improved when trastuzumab (HER-2 receptor antagonist) was added to therapy. Trastuzumab is used to treat metastatic (spread) breast cancer. It is effective against tumors that overexpress the HER2/neu protein. It is effective against tumors that overexpress the HER2/neu protein as a part of chemotherapy regimen for adjuvant

17

Introduction to Personalized Medicine and Pharmacogenomics

281

treatment of lymph-node positive, HER2/neu protein positive breast cancer (Slamon et al. 2011). Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes. Melanomas typically occur in the skin but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In most cases, melanoma is caused by exposure to ultraviolet (UV) radiation from the sun or tanning beds (Heistein and Acharya 2021). It damages the DNA of your skin cells, and they start to grow out of control. A specific mutational change in the BRAF (a human gene that encodes a protein called B-Raf) gene, which makes a protein that is involved in sending signals in cells and in cell growth. This BRAF gene mutation may be found in some types of cancer such as melanoma and colorectal cancer. It may increase the growth and spread of cancer cells (Hussain et al. 2015). Vemurafenib (proto-oncogene protein BRAF inhibitor) is the first molecularly targeted therapy to be licensed in the USA and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signaling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Vemurafenib only works in patients whose cancer tests positive for the V600E BRAF mutation (Sharma et al. 2012). Around 60% of patients with melanoma have a BRAF mutation, and approximately 90% of those are BRAF V600E mutation (Cheng et al. 2018). The heart transplantation is a critical surgical procedure which is performed on patients with failing heart. This procedure runs a very high risk of transplant rejection. In order to predict the chances of transplant rejection, one has to do the heart biopsy and perform the test using the sample. Personalized medicine development has led to a test using blood sample instead of heart biopsy. The gene expression profiling test using blood sample to predicting chances of the rejecting transplant organ has saved patients from heart biopsy. Now one can identify by a genetic test performed on blood sample. This test can also be used in monitoring the development of changes in patient pathology leading to transplant rejection. It can be used in guiding immunosuppressive therapy for post-surgery (Nasr et al. 2016). Personalized medicine is a multifaceted method in patient care. It is very much useful in accurate diagnosis and treatment. For this, it is also known as precision medicine. Especially in cancer it offers an opportunity to identify the development of the disease in early stages. It is interesting to know if the cancer is treated in early stages, it is very simple, and one can cure cancer easily. It is useful in risk assessment. For example, with the identification of biomarkers, one can perform genetic testing which can reveal chances of predisposition to a disease (Novelli et al. 2008). Personalized medicine can be very much useful in the prevention of diseases and make a big change in public health. It can be used to alert the concerned public to modify lifestyle changes and risk behavior which can be helpful in adopting the preventive health measures. The research in genetic engineering has made it possible to read the pathological changes at molecular level (Vogenberg et al. 2010). Previous medical approaches have been based upon a policy of “one size fits all,” applying the

282

A. N. Nagappa and S. Bhatt

same treatments to those with the same diseases. However, this has many limitations as there are a whole range of disease contributing factors, including genetics and environments, which affect the efficacy of certain medications (Vogenberg et al. 2010; Brothers and Rothstein 2015). Through genome analysis, scientists can personalize drugs to make them more specific and effective, thereby improving treatment outcomes. However, there are several drawbacks to this approach. This article aims to discuss the pros and cons of personalized medicine and assess its possible future roles.

17.2

Advantages of Personalized Medicine

There are many advantages of the applications of personalized medicine within healthcare. Firstly, this approach can be used to detect and diagnose diseases in a highly specific manner, categorizing them by genetic variation rather than by symptom. This allows treatments which are increasingly specific and effective, improving the prognosis of many disorders (Goetz and Schork 2018). For example, melanomas which have a specific mutation in the BRAF gene can be targeted by a highly specific, BRAF targeting drug. Typical treatment for melanomas is not viable in these patients, and therefore this treatment dramatically increases prognosis. Additionally, genomic analysis can reveal genetic variations which can guide drug dosage, meaning that patients can get maximal drug benefit with minimal side effects. This has been applied to a whole range of diseases so far, such as cancer, mental illness, and inflammatory bowel disease (Holderfield et al. 2014). One such example is the detection of specific variations within CYP450 genes. There are many different variations of these genes, which are involved in the metabolism of a whole plethora of drugs (Tracy et al. 2016). Therefore, identification of specific gene variants allows the prescription of drugs at effective levels while minimizing harmful side effects. Another application of personalized medicine is within the prevention of disease. Using sequencing technologies, susceptibility to disease can be analyzed, allowing a focus upon prevention with both treatments and lifestyle changes. For example, women who have variations of BRCA1/BRCA2 have an over 80% chance of developing breast cancer and 60% chance of developing ovarian cancer (Petrucelli et al. 1998). Detecting these variants therefore allows preventative surgery and chemotherapy treatments. Another advantage of personalized medicine is the reduction of trial-and-error prescriptions. Initial prescriptions are often not effective due to genetic variations, meaning that patients must try a range of drugs to find one that works for them. However, by analyzing patient’s genome, more specific drugs can be prescribed, giving more effective benefits, reducing the time required to identify effective drugs, and minimizing the cost of healthcare (Vogenberg et al. 2010; Aneesh et al. 2009). The expense of healthcare is greatly increased when patients do not adhere to treatments, as this often leads to additional health problems. However, the greater effectiveness and minimal harmful side effects of personalized medicines can motivate patients to adhere to their medications, reducing the cost and increasing

17

Introduction to Personalized Medicine and Pharmacogenomics

283

prognosis. Personalized medicine approaches can detect genetic predisposition to high cholesterol, which can make patients stick to their lifestyle changes as they understand the risk (https://www.news-medical.net/health/Is-Personalized-Medi cine-the-Future-of-Healthcare.aspx). There are also many drawbacks of personalized medicine despite its numerous benefits, as previously described, which could prevent it from becoming the future of healthcare. A major concern of the increased use of personalized medicine is the ethical issue of patient privacy. For example, there are concerns that some may not use this information in an ethical way, such as insurance companies who may not offer certain policies to those with genetic predisposition. There are also other ethical concerns, such as incidental findings. Locating a life-altering disease which has no treatment options is arguably unethical, as knowledge of these diseases can lead to mental health problems and can have a huge impact on a patient’s life. Additionally, incorrect findings are also an unethical problem, as they can lead to unrequired expense of healthcare and psychological issues (Brothers and Rothstein 2015; CruzCorreia et al. 2018). Furthermore, there are many issues within the legal sector. For example, there are problems within intellectual property rights, as some argue that making advancements only available to some will hold back the development of future personalized medicines. Additionally, regulation laws will have to be reassessed, as they currently cannot be applied to personalized medicine (Brothers and Rothstein 2015).

17.3

What’s Next?

Overall, there are many ethical and legal issues which pose a threat to the future of personalized medicine. However, there is no denying that there are copious advantages within this approach to medical care, with increased effectiveness and minimal side effects. Therefore, it could be argued that, overall, the future of healthcare is personalized medicine (Vogenberg et al. 2010; Goetz and Schork 2018). Figure 17.2 explains the concept of genetic polymorphism. Currently, patient support and education are lacking in many areas which hinder the ability of patients to actively participate in their healthcare decision-making process even though most want to be involved. In fact, about two-thirds (64%) of interstitial lung disease patients experience stress due to a lack of understanding about their disease (Longtin et al. 2010). In addition, as a recent article in Nature noted, an estimated 90% of conventional and top-selling blockbuster medicines only work for 30% to 50% of patients. For some, these medications aren’t just ineffective, but they also cause adverse reactions and side effects. Therefore, market sizes for some meds may be reduced as medical advances and accumulated data allow us to determine which patient segments are likely to respond poorly to a drug. Patients may also become increasingly frustrated as they struggle to better understand expanding treatment options (https://www.forbes.com/sites/reenitadas/2017/03/08/

284

A. N. Nagappa and S. Bhatt

Fig. 17.2 Concept of genetic polymorphism

drug-development-industry-bets-big-on-precision-medicine-5-top-trends-shapingfuture-care-delivery/?sh¼47778cde5d3a).

17.4

Opportunities

On the other hand, non-adherence to medication can be reduced when patients’ preferences and lifestyle are considered. Segmenting appropriate patients for targeted therapies can also produce better results and higher satisfaction (Jimmy and Jose 2011). Lastly, there is a competitive edge opportunity for pharma companies who help bridge the communication gap between HCPs and patients for better shared decision-making as the demand for personalized medicine increases. Outcome Health, a health information platform provider formerly called Context Media, says that compared to a control, for each dollar spent on a personalized digital interactive marketing campaign, brands are earning as much as $7 through an incremental lift on prescriptions filled. In terms of adherence, some are seeing a lift of more than 80% in continued prescriptions (https://rnsights.com/ the-push-for-personalized-medicine/).

17.5

Personalized Medicine Requires Personalized Marketing

Pharma marketers must improve their personalized marketing to keep up with the personalized medicine movement. Besides market segmentation, pharma marketers should also increase focus on ways to improve communication between HCPs and patients for shared decision-making. For example, evidence shows that specialist nurses have a significant beneficial impact on personalized patient care, education, communication, and adherence to treatment (https://rnsights.com/the-push-forpersonalized-medicine/). Studies show that the support from frequent, patientmanaged discussions with specialist nurses results in patients reporting higher satisfaction, “feeling in control,” “knowing what to expect from treatment,” and

17

Introduction to Personalized Medicine and Pharmacogenomics

285

confidence about their disease management. Pharma marketers, therefore, need to support nurses as many ways as they can including providing educational tools and resources (https://rnsights.com/the-push-for-personalized-medicine/; Duck et al. 2015). One example is patient decision aids designed to help patients understand and consider the pros and cons of possible treatment options and to encourage communication between HCPs and patients. They should be available to nurses, feature evidence-based information, and contain images or diagrams where appropriate (Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population; Board on Health Care Services; Institute of Medicine, et al. 2013). Providing apps and digital health technologies can also be a competitive edge. Last month, Apple announced an update to the Health app debuting a feature for customers to see their medical records right on their iPhone. Ultimately, “we’re hoping to enable richer conversations between doctor and patient,” said Sumbul Desai, Apple’s digital health lead who’s also a physician and medical researcher. One can easily conclude that the ability to pull up your own health record on an iPhone will only feed the desire for even more precision medicine and the demand for patients to have greater participation in treatment discussions. Decisions will increasingly be made as a much more collaborative effort between HCP interdisciplinary teams and patients. Pharma marketers should seize the opportunities created from this personalized medicine movement where HCPs and patients must find ways to bridge their communication gap for shared decision-making (Bush et al. 2019).

17.6

Conclusion

Personalized medicine may be soon considered as preferred approach for the treatment of various chronic and severe diseases. This approach is used in various developed countries in which severe diseases can be treated in better way based on the genetic makeup of individual. Hope soon the approach will gain access in developing countries.

References Agyeman AA, Ofori-Asenso R (2015) Perspective: does personalized medicine hold the future for medicine? J Pharm Bioallied Sci 7(3):239–244 Aneesh TP, Sekhar MS, Jose A, Chandran L, Zachariah SM (2009) Pharmacogenomics: the right drug to the right person. J Clin Med Res 1(4):191–194 Brothers KB, Rothstein MA (2015) Ethical, legal and social implications of incorporating personalized medicine into healthcare. Pers Med 12(1):43–51. https://doi.org/10.2217/pme. 14.65 Bush WS, Cooke Bailey JN, Beno MF, Crawford DC (2019) Bridging the gaps in personalized medicine value assessment: a review of the need for outcome metrics across stakeholders and scientific disciplines. Public Health Genomics 22(1–2):16–24

286

A. N. Nagappa and S. Bhatt

Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R (2018) Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol 31(1):24–38 Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population; Board on Health Care Services; Institute of Medicine, Levit L, Balogh E, Nass S et al (2013) Patient-centered communication and shared decision making. In: Delivering highquality cancer care: charting a new course for a system in crisis. National Academies Press, Washington Cruz-Correia R, Ferreira D, Bacelar G et al (2018) Personalised medicine challenges: quality of data. Int J Data Sci Anal 6:251–259 Cutter GR, Liu Y (2012) Personalized medicine: the return of the house call? Neurol Clinl Pract 2(4):343–351 Duck A, Pigram L, Errhalt P et al (2015) IPF care: a support program for patients with idiopathic pulmonary fibrosis treated with Pirfenidone in Europe. Adv Ther 32:87–107 Godman B, Finlayson AE, Cheema PK et al (2013) Personalizing health care: feasibility and future implications. BMC Med 11:179 Goetz LH, Schork NJ (2018) Personalized medicine: motivation, challenges, and progress. Fertil Steril 109(6):952–963 Heistein JB, Acharya U (2021) Malignant melanoma. StatPearls Publishing, Treasure Island Holderfield M, Deuker MM, McCormick F, McMahon M (2014) Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer 14(7):455–467 Hussain MR, Baig M, Mohamoud HS, Ulhaq Z, Hoessli DC, Khogeer GS, Al-Sayed RR, Al-Aama JY (2015) BRAF gene: from human cancers to developmental syndromes. Saudi J Biol Sci 22(4):359–373 Institute of Medicine (US) Committee on Assuring the Health of the Public in the 21st Century (2002) The health care delivery system. In: The future of the public's health in the 21st century. National Academies Press, Washington Iqbal N, Iqbal N (2014) Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Molecul Biol Int 2014:852748 Jimmy B, Jose J (2011) Patient medication adherence: measures in daily practice. Oman Med J 26(3):155–159 Longtin Y, Sax H, Leape LL, Sheridan SE, Donaldson L, Pittet D (2010) Patient participation: current knowledge and applicability to patient safety. Mayo Clin Proc 85(1):53–62 Nasr M, Sigdel T, Sarwal M (2016) Advances in diagnostics for transplant rejection. Expert Rev Mol Diagn 16(10):1121–1132 Novelli G, Ciccacci C, Borgiani P, Papaluca Amati M, Abadie E (2008) Genetic tests and genomic biomarkers: regulation, qualification and validation. Clin Cases Miner Bone Metab 5(2): 149–154 Petrucelli N, Daly MB, Pal T (1998) BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews®. University of Washington, Seattle Sharma A, Shah SR, Illum H, Dowell J (2012) Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies. Drugs 72(17): 2207–2222 Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283 Tracy TS, Chaudhry AS, Prasad B, Thummel KE, Schuetz EG, Zhong XB, Tien YC, Jeong H, Pan X, Shireman LM, Tay-Sontheimer J, Lin YS (2016) Interindividual variability in cytochrome P450-mediated drug metabolism. Drug Metab Dispos 44(3):343–351 Vogenberg FR, Isaacson Barash C, Pursel M (2010) Personalized medicine: part 1: evolution and development into theranostics. P & T 35(10):560–576

Introduction to Pharmacoeconomics and Outcome Research

18

A. N. Nagappa and Shvetank Bhatt

Abstract

Costs of treatments by modern medicine have significantly increased causing accessibility and affordability problems. The patent protections for new drugs have killed the competition and have given the patent holder to become super rich at the cost of patients’ health. Pharmacoeconomics and outcome research have helped the government to understand the dynamics of drug price and its impact on accessibility and affordability. Outcome research is helpful in rationalizing the drug therapy and making drug therapy from product-centric to patient-centric. Keywords

Cost-outcome analysis · Cost of illness · Cost-benefit analysis · Quality-of-life studies

Medical treatments are becoming not only clandestine but also unreasonably expensive. Many patients across the world who lack subscription to health insurance have to pay medical expenses by out of the pocket. Treatment of certain chronic disease and conditions is very expensive and patients may become bankrupt in order to survive. On average, 40% of the treatment bill is for medicines. Medicine prices play an important role as for the cost of treatment is concerned (Institute of Medicine (US) Committee on the Consequences of Uninsurance 2002). The patient community is the only the sufferer among the stakeholders. Patients are dependent on advice and recommendation of the doctors, and due to their ignorance, they are easily exploited, for example, doctors never take interest in the A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_18

287

288

A. N. Nagappa and S. Bhatt

price of medicines as they were motivated to prescribe brand medicines promoting pharmaceutical industries although in the open market there are equivalent inexpensive generic medicines available. Moreover, patients discharged are advised not to use those medicines but to use expensive brand medicines (Roy and Rana 2018). Apart from these, adverse effects of medicine play a role in the choice of medicines. Medicines may be very good in terms of efficacy if the molecule has serious adverse drug reactions than those drugs that cannot be used. In such circumstances, the doctor demands risk-benefit analysis and also comparative study of alternative treatments. In order to assess quantitatively the value of the treatment, one has to carry out pharmacoeconomic analysis. Pharmacoeconomic analysis is divvied into partial and full pharmacoeconomic evaluations. In partial economic evaluation, there are cost-consequence analyses or cost-outcome analysis and cost-of-illness evaluation. In full pharmacoeconomic analysis, we have cost minimization analysis, cost-benefit analysis, cost-effective analysis, and cost-utility analysis (Tunis 2009). The value of resources consumed by drug therapy is defined as cost; healthcare costs are classified as direct medical costs, direct nonmedical costs, indirect nonmedical costs, intangible costs, opportunity costs, and incremental costs. Direct costs are those direct medical costs plus direct nonmedical costs. Indirect costs are morbidity costs plus mortality costs, total costs, and direct costs plus indirect costs plus intangible costs (Tunis 2009). Direct medical costs include the money spent on drugs, medical supplies, equipment, laboratory, diagnostic test, hospitalization, and physician fee. An indirect medical cost is the expenditures for patients and includes the attendant’s bus fare from his/her home to hospitals. It also includes extra trips undertaken to the emergency department. One should also include out-of-pocket expenses for child or family care, special diet, and various other expenses. Indirect nonmedical costs are the costs due to loss of productivity during illness. It also includes loss of years of service due to premature death. Nonfinancial outcomes of disease and medical care such as grief inconvenience, pain, and suffering are computed as intangible costs. The economic benefit or value that was forgone by not choosing the alternative therapy is the opportunity costs. The incremental costs are those which need to be spent to purchase an addition unit of effect (Yousefi et al. 2014). Before pharmacoeconomic analysis is undertaken, one should clarify on whose perspective the analysis is carried out. Common perspective includes the patient’s perspective who is worried about the portion of the costs which he/she has to bear as those costs are not covered by health insurance as there is no subsidy by the third parties, like government or any philanthropic agencies. In provider’s perspective, evaluation is based on direct costs which are important for the hospital administration. When we are caring out pharmacoeconomic analysis on behalf of health insurance company employers or the government, we are calculating a pair perspective. The society’s perspective includes the total cost calculated for the whole society which includes all direct and indirect costs (Ahmad et al. 2013). Treatment consequences are defined as the effects or outputs/outcomes of a drug therapy. There can be three types of outcomes which are also combined in echo

18

Introduction to Pharmacoeconomics and Outcome Research

289

model. The economic outcomes involve comparing direct, indirect, and intangible costs of a treatment with another alternative treatment. Clinical outcomes are the outcomes of treatment events that occur due to treatment or disease, for example, efficacy end points or therapy end points (Jo 2014). These are very much important for doctors to assess the patient’s response to disease. Clinicians are more concerned with clinical outcomes; the humanistic outcomes are the consequences of disease or treatment on patient’s functional status such as mobility, physical function, social function, general health, well-being, and quality of life with satisfaction as experienced by the patient. There can be positive outcomes (desired effect of a drug), negative outcomes (ADR or toxicity of a drugs), and intermediate outcomes which can serve as a proxy for more relevant final outcomes. The final outcomes can be compute on the basis of patient’s expression i.e. in case of myocardial infarction the final outcome will be reduction in the severity of the disease and patient’s symptoms by the treatment of lipid lowering agents (Feingold 2000).

18.1

Partial Pharmacoeconomic Analysis

Partial economic evaluations included simple descriptive tabulation of outcomes or resource consumed. These evaluations require a minimum time and efforts: 1. Cost-consequence analysis is also known as cost-outcome analysis: A costconsequence analysis compares the health interventions of interest to one or more relevant alternatives, listing the cost component and various outcomes of each interventions separately (Table 18.1). There are few assumptions made in cost-consequence study, analysis dose, not combined cost, and consequence of interventions making table of cost and consequence. The user of the method should independently reach at a decision which is the better alternative among the choices. The cost-consequence study provides a compressive presentation of cost and value of the intervention. The cost-consequence study lists the cost and outcome in the following manner (Stergachis 1995): • Direct medical costs • Direct nonmedical costs • Indirect costs (time cost, productive costs) • Health-relative quality-of-life impact • Utility impact • Clinical outcomes (including side effects, adverse events) (Jo 2014) 2. Cost-of-illness analysis: Cost-of-illness evaluations identify and estimate the overall costs of a particular disease for a defined population. It is also known as burden of illness. It mainly involves computing direct and indirect costs attributable to a specific disease such as cancer, hypertension, or diabetes. Cost-of-illness evaluation is not used to compare alternative treatments but to provide an estimation of a financial burden of a disease (Jo 2014).

290

A. N. Nagappa and S. Bhatt

Table 18.1 Example of a cost-consequence table Intervention A Units Cost

Intervention B Units Cost

Direct medical costs Intervention A/B Other medication/ interventions Physician office visits ER visits Hospitalizations Home care Direct nonmedical costs Transportation Paid caregiver time Indirect nonmedical costs Patient time missed from work Unpaid caregiver time off from work Symptom impact Patient distress days Patient disability days Adverse events Serious adverse events Moderate adverse events Mild adverse events Health-related quality-of-life impact Quality-adjusted life years Quality-of-life profile

Cost-of-illness analysis aims to determine the total economic impact of a disease or health condition on society through identification, measurement, and valuation of all direct and indirect costs. This one does not address the issues relating to treatment efficiency. Cost-of-illness analysis is adopting societal perspective which is useful in measuring the financial burden due to disease on sectors like state or federal government, specific institutions, or organization such as employers and health insurances. It also can be used by individuals to assess the financial burden due to a disease or condition he/she suffering. It is the costumer who estimates the cost of an illness which is an annual basis for a particular disease or condition (Jo 2014). Further the approach provides an estimate of the lifetime cost of incident cases diagnosed in a particular year. The direct cost can be calculated using top-down or bottom-up costing techniques or sometimes both. Indirect cost arises from lost economic activity due to illness. These are calculated by using human capital method

18

Introduction to Pharmacoeconomics and Outcome Research

291

that includes the stock knowledge, habits, and social and personality attributes, including creativity, embodied in the ability to perform labor so as to produce economic value. On the other hand, friction cost method is a method that estimates the indirect cost due to productivity loss (https://www.euro.who.int/__data/assets/ pdf_file/0007/144196/e95096.pdf). Cost-of-illness studies help one to measure the total expenditure spent on particular diseases in comparison to the scope of health problem. Comparison can be theoretically computed across different diseases, for example, cost of illness for asthma, hypertension, diabetes, and breast cancer prevention. Cost-of-illness studies provide a market measure for the pharmaceutical manufacturer with respect to assessing the market size and treatment pattern of specific health problem and diseases (Hernlund et al. 2013).

18.2

Full Pharmacoeconomic Analysis

1. Cost-minimization analysis is a type of pharmacoeconomic analysis comparing two alternative therapies only in terms of costs because their outcomes (effectiveness and safety) are found to be or expected to be identical. The economic analysis of medical technologies, in general, and pharmaceutical therapies, in particular, is based on the principle of comparing alternatives in terms of costs and of health outcomes. The principal types of analysis are costconsequence analysis, cost-minimization analysis, cost-effective analysis, costutility analysis, and cost-benefit analysis (Robinson 1993). Cost-minimization analysis has an advantage because in this analysis health outcomes are assumed to be equivalent and the choice of preferred alternative will be the least expensive. However, practically value and utility of costminimization analysis are very limited for assessing new medical interventions. New intervention should have demonstrated a better efficacy profile with less side effects to be accepted by regulatory authorities. Sometimes Cost-minimization analysis is also used to compare me-too drugs. The most valuable analysis would be between two drugs belong to same class, having similar efficacy and safety but differing in formulation, for example cost-minimization analysis for a tablet versus Intravenous infusion, i.e. Paracetamol tablet versus Paracetamol injection. Paracetamol tablet price is INR 2.8 per unit, while paracetamol injection price is INR 50 per unit. Cost-minimization analysis is useful in assessing me-too drugs where clinical outcome does not be able to assess, but comparison can be on differences in acquisition cost and administrative cost like differences in nonmedical cost such as patients time value (https://www.who.int/medicines/ technical_briefing/tbs/06-PG_Evaluating-drug-costs_final-APRIL-25-2008.pdf). It is recommended to apply statistical test when only the objective of the study is to highlight cost difference but not the clinical efficacy. 2. Cost-benefit analysis: Cost-benefit analysis is an analytical technique that compares and enumerates the cost of a healthcare intervention with the derived benefits as a consequence of intervention. It is based on economic theory which

292

A. N. Nagappa and S. Bhatt

considers net cost and the benefits of health interventions which are expressed in terms of monitory units. The punch line of the analysis is determination of net benefits which is the benefits—the net cost is the net benefit. Net benefits are the basic decision criterion in cost-benefit analysis. If the net benefit is positive, one can accept the decision. However, sometimes analysis computes for cost-benefit ratio or benefit-cost ratio. Cost-benefit analysis is usually carried out for a societal perspective. It tries to include all the relevant cost and outcomes. The major advantage of cost-benefit analysis is it allows the compression of two different programs—interventions which may be unrelated as far as outcomes are considered. It is possible to compare two completely unrelated programs strictly on a monitoring value. The choice of the intervention is usually based on the highest net benefits (https://www.nlm.nih.gov/nichsr/hta101/ta10107.html). Further, it can be a unique technique that has a definitive self-contain decision rule for evaluating even single intervention; if net benefit intervention is positive, it is worth to perceive further. One should understand here that cost-benefit analysis is not to be used to compare alternative therapies due to ethical concerns which compare human livelihood against monitory value. A key disadvantage of this type of analysis is the difficulty of converting nonmonetary clinical and quality-of-life outcomes such as years saved life and saved into monetary units. Moreover, usually method of making this translation i.e. willingness to pay seems to be unethical as more weightage and preference is given to the rich people. Cost-benefits analysis is usually based on a model which requires significant assumption. Hence, it becomes very important to validate the model assumptions and to determine robustness of the result by a sensitivity analysis. 3. Cost-effective analysis: Cost-effective analysis is a comparison between two treatments and is usually expressed graphically called as cost-effectiveness acceptability curb which plots the probability of one treatment against another in terms of willingness to pay for one additional unit of efficacy. It is a systematic method of comparing two or more alternative programs by measuring the cost and consequence of each (health outcomes). The striking feature of cost-effective analysis is the health outcomes of alternative intervention are compared and must be measured in the same common units, for example, symptom-free days gained, cases prevented, number of patients improved, and life years gained (https:// www.nlm.nih.gov/nichsr/hta101/ta10107.html). In cost-effective analysis, if there are only two treatments, then the incremental cost (deferent in cost) is compared to their difference in outcomes (increments effect). One can calculate incremental cost-effectiveness ratio (ICER) by dividing incremental cost by incremental effect. If there are more than two alternatives, the ICER is calculated by comparing incremental effect with incremental cost of individual treatments. CEA is the most popular technique of pharmacoeconomics to enhance the compatibility across different cost-effectiveness studies. It is recommended to include reference case. The reference case prescribes the standard approaches like how to measure cost and effectiveness. It also has details of application of quality-adjusted life years whose preferences are also used to calculate its

18

Introduction to Pharmacoeconomics and Outcome Research

293

quality-adjusted life years. The advantage of conducting reference case analysis before doing real analysis is it has built-in concept and assumptions needed in making comparisons across different cost-effectiveness studies. The reference case used in a cost-effective analysis usually is based on compressive societal perfective (Franklin et al. 2019). 4. Cost-utility analysis: Cost-utility analysis is a method of economic analysis in which two or more alternative therapies are compared in terms of money and outcome or utility. The utility is often measured in the units of quality-adjusted life years. The objective of cost-utility analysis is to compare using costeffectiveness of two or more alternatives in terms of clinical and economic value. Cost-utility analysis is considered as a benchmark methodology for evaluating cost-effectiveness of healthcare alternatives. In this analysis, the denominator is measured in terms of quality-adjusted life years gained by the treatment. It is important because it allows the cost utility measured to be compared with alternative treatments and allows one to decide the level of acceptance of cost utility for healthcare alternatives. In Cost Benefit Analysis, terms of threshold level (cost/QALY), which uses intermediate outcomes such as cost per infection cured or cost per Cancer detected. In cost-benefit analysis, which uses the human capital method to evaluate survival effects, which can be not equitable when comparing some groups such as males and females or the elderly and adults as this measured depends on ones ability to earn money. Cost-utility analysis is a methodology which overcomes these deficiencies of cost-benefit analysis and cost-effective analysis. In addition, cost-utility analysis has the advantage of including quality adjustments which are very important when the two alternative choices defer in the effects on quality of life and also on survival. Cost-utility analysis is expressed in terms of ratio of the incremental cost of alternatives over the incremental quality-adjusted life years of the alternative treatments. The result shows the amount of saving cost and its relation to quality-adjusted life year for particular a treatment (https://www.nlm.nih.gov/nichsr/hta101/ta10107.html) (Ryder et al. 2009). Cost-utility analysis is used to determine the relative value of alternative healthcare programs. It is very much similar to cost-effective analysis but defers in its use of QALYs as the measurement of outcome in the denominator. The denominator in the cost/utility ratio is the incremental gain in QALYs for comparing the alternatives programs. Advantage of using QALYs as an outcome measure allows comparability across all cost utility analysis studies. QALYs is an universal measure can be applied to all the patients and all the diseases. QALYs provide the common matrix which enables decision-maker to compare CUA ratios. Quality weights for QALYs are based on individual preferences for different health states. It can be directly measured by instrument such as slandered gamble, time trade-off, or visual analog scale. On the other hand, quality weights are available such as multi-attribute utility indexes, EuroQal EQ-5Q, or Quality of

294

A. N. Nagappa and S. Bhatt

Well-Being (Health Utilities Index). QALYs are calculated by summing the survival years and the utility for each year of survival. If the survival year is spent in perfect health, that is multiplied by one and has the full value; however, if the year is spent in a health state of 0.6, that year survival is 1
0.6 ¼ 0.6 QALYs. In all 5 years of survival due to an intervention which have a 0.6 utility value, the total QALYs for that intervention is calculated as 5
0.6 ¼ 3 QALYs. If the alternative intervention has the same survival of 5 years with perfect health than the QALYs is 5
1 ¼ 5 QALYs. Incremental CUA is calculated. B versus A is calculated as (Cost B – Cost A)/QALYs of B – QALYs of A). If the cost of intervention B is 50.000 and cost of A is 30.000 and if the QALYs of B are 5 and QALYs of A are 3, then intervention B is more costly as described above. However, intervention B is more expensive which provided more QALYs than incremental CUA is INR 50,000/−-INR 30,000/−) /(5-3) ¼ INR 20,000/− 2QALYs or INR 10,000/− Per QALYs. Therefore, it costs an additional of INR 10,000 per each QALY gain to choose from alternative B or alternative A. Example: Calculate the cost-utility analysis to compare the coronary angioplasty versus coronary artery bypass graft (CABG). Step one: Identify the two alternative decisions. Strategy A, coronary angioplasty, is a procedure used to widen blocked or narrowed coronary arteries (the main blood vessels supplying the heart). Strategy B, coronary artery bypass graft (CABG), is a type of surgery that improves blood flow to the heart. Surgeons use CABG to treat people who have severe coronary heart disease (CHD). Step Two Gather outcome data, utility data, cost data, and clinical trial data which are used to assess survival at 5 years with the use or nonuse of CABG in patients. Utility study which measured the utility of different health states with coronary artery disease with or without coronary angioplasty is used to adjust survival to account for the effects of the side effects of coronary angioplasty and the effect of CABG itself on subjects. Costs were estimated from a combination of the literature, Medicare costs, and locally derived costs. Step Three Determine life expectancy, utility, and cost.

Strategy A: No. test, no interferon Strategy B: SLN test, interferon to positives

Calculate the incremental CUA:

Quality adjusted Survival (years) 3.06 4

Costs INR125000/ INR150000/

18

Introduction to Pharmacoeconomics and Outcome Research

CUA ¼

295

Cost Strategy B  Cost Strategy A QALY Strategy B  QALY Strategy A ¼

150000  125000 4  3:06 CUA ¼

25000 04

¼ 62500=  Per QALYs It costs an additional of 62,500/ per additional QALYs saved if we choose CABG over coronary angioplasty. This is below the often used cut of threshold of 1 lakh per QALYs, and therefore, CABG is a cost-effective choice.

18.3

Outcome Research

Outcome research is a recent phenomenon which revolves around the concept of patient-centric care. The history of clinical practice is dominated by clinical outcomes, and hardly any importance was given for the cost of the treatment or how the patient feels during and after treatment. Patients are very important stakeholders who are responsible for funding the treatment expenses directly or indirectly. To elaborate further, a patient pays for the treatment by out of his/her pocket or through funding agency like health insurance company and government. In fact the health insurance companies are funded by patients, who purchase the insurance policies. Of course the government collects the tax from the people and funds the health budget (Committee on the Learning Health Care System in America; Institute of Medicine, et al. 2013). The patients directly or indirectly are responsible for arranging the funds for treatments. In the course of treatment, many patients feel exhausted due to either unable to meet the treatment cost or unable to bear the morbidity due to treatment itself, for example, cancer. In cancer treatment, a lot of money has to be spent on drugs and also on hospitalization. The patient and his family become bankrupt and also psychotically depressed due to the deteriorating condition of the patients. These incidences were the seeds for development of pharmacoeconomic and outcome research. Pharmacoeconomic has been discussed in great details previously. The outcome research measures the functional status, health status, and quality of life of the patient undergoing treatments. They are summarily called as humanistic outcomes (Institute of Medicine (US) Committee on Psychosocial Services to Cancer Patients/Families in a Community Setting et al. 2008). Initially the humanistic outcome emerged as an observation study which aimed at documenting clinical, economic, and/or humanist outcomes along with the treatment. The outcome research becomes more scientific by developing observation study into a formal experimental design. The clinical outcomes are usually quantitative or qualitative data which can be subjected to statistical analysis, whereas the

296

A. N. Nagappa and S. Bhatt

outcome research data is usually a descriptive data expressed by the patient through an instrument of questionnaire. This means the outcome research has a great drop back as far as the prediction of the patient preferences and satisfaction are concerned. The outcome research should also be defined on whose perspective the research is conducted. For example, the outcome research can be aimed at patient perspective or provided perspective. It may be also be carried out from the point of health insurance companies or the government. There are various instruments designed and validated for the purpose of measurement of quality of life. The instruments of quality of life are divided into generic and disease-specific instrument. These instruments are available in public and private domains; the instruments available in private domain are charged fee for doing an outcome research. Generic questionnaire collects information about the patient well-being in terms of questionnaires which are commonly used to gather first-hand information from a large audience, in the form of a survey. There are different types of questionnaires in practice, and the type of questionnaire to be used usually depends on the purpose of the survey and the type of data that has to be collected. Questionnaires are highly practical and can be carried out by any number of people, and the results can be quickly quantified as well. Over the years, this form of conducting research has also been proven to be more scientifically accurate, as compared to other quantitative research tools.

18.3.1 Questionnaire Formats Depending upon the nature of the questions in a questionnaire, there can be different types of questions in questionnaire.

18.3.2 Questions in an Open-Ended Format Questions that allow the target audience to voice their feelings and notions freely are called open-format questions or open-ended questions.

18.3.3 Questions in a Closed-Ended Format Questions which have multiple options as answers and allow respondents to select a single option from among them are called closed-format or closed-ended questions.

18.3.3.1 Types of Closed-Format Questions Closed-ended questions which are aimed at collecting accurate statistical data can be classified into the following seven types:

18

Introduction to Pharmacoeconomics and Outcome Research

297

Leading Questions A question forcing the target audience to opt for a specific kind of answer is called a leading question.

Importance Questions Questions which ask respondents to rate the importance of some specific matter on a rating scale of 1 to 5 are called importance questions.

Likert Questions The degree to which respondents agree to a specific statement can be ascertained using Likert questions.

Dichotomous Questions Questions that make respondents answer with a simple “yes” or “no” are called dichotomous questions.

Bipolar Questions Questions that have two answers with different levels of extremities, written at opposite ends of a scale, are called bipolar questions.

Rating Scale Questions Questions that ask respondents to provide a rating on a specific matter on a scale of 1 to 10 or on a scale of “poor” to “good” are called rating scale questions.

Buying Propensity Questions These are aimed at assessing customers’ future intentions and determining their propensity toward buying a specific product or service.

Other Types of Questionnaires Apart from the abovementioned two broad classifications, there are two more types which are rarely used in practice, namely, mixed questionnaire and pictorial questionnaire. Mixed questionnaires consist of closed as well as open-ended questions. These are normally used in the field of social research. Pictorial questionnaire on the other hand is used in promotion of interest to answer questions. These are mostly used as study material for children.

298

18.4

A. N. Nagappa and S. Bhatt

Different Types of Quality Life Insurance

18.4.1 Generic Instrument 18.4.1.1 Disease-Specific Instrument Generic Instrument These instruments were applicable to all persons irrespective of their type or number of disease, but they may not be sensitive to some problems unique to particular disease. Examples for generic QOL instruments were summarized in Table 18.2.

Advantages of Generic Instruments 1. Generic instruments are suitable across a broad range of health problems. 2. They can be used for comparing treatments of different patient groups to assess comparative effectiveness. 3. They can also be used in healthy populations to get generic normative data that can be used to compare different patient groups. 4. Useful for asserting the impact of new healthcare technologies when the therapeutic effects are uncertain.

Disadvantages of Generic Instruments 1. Limitation for the relevance of generic instruments when applied to a specific patient population. 2. Generic instruments are potentially less responsive to clinical important changes in health.

18.4.1.2 Disease-Specific Instruments These instruments are used to measure the patient’s perceptions of a specific disease or health problems. Examples for disease-specific QOL instruments were summarized in Table 18.3. Table 18.2 Example of generic instrument S. no. 1 2 3 4 5 6 7 8

Name of instruments Medical outcomes study 36-item short form (SF-36) health survey Nottingham health profile (NHP) Quality of Well-being (QWB) scale EuroQol instrument (EQ-5D) Sickness impact profile (SIP) Health utilities index (HUI) World Health Organization quality of life instruments (WHOQOL-100 and WHOQOLBref) Dartmouth primary care cooperative information project (COOP) charts

18

Introduction to Pharmacoeconomics and Outcome Research

299

Table 18.3 Example for disease-specific QOL instruments S. no. 1

Name of instruments Dermatology life quality index (DLQI)

2 3 4 5 6

Kidney disease quality of life short form (KDQOL-SF) Asthma quality of life questionnaire (AQLQ) Diabetes quality of life measure (DQOL) HIV-AIDS-targeted quality of life instrument European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C 30 The MacNew

7

Disease Skin and connective tissue disease Kidney disease Asthma Diabetes HIV/AIDS Cancer Heart disease

Advantages of Disease-Specific Instruments 1. These are diseases-specific instruments to a particular disease and clinically relevant. 2. Disease-specific instruments do not contain any items or health dimensions that are not related to the disease. 3. Instruments have clear relevance to patients with the presenting problem; acceptability is likely to be high. 4. These instruments can be used for economic evaluation including cost-utility analysis.

Disadvantages of Disease-Specific Instruments 1. It is not possible to administer diseases-specific instruments to patients who do not have the specific health problem. 2. It is not possible to make comparisons across treatments for different disease, which limits the application of diseases-specific instruments in economic evaluation.

Examples of Quality-of-Life Domains Quality-of-life instruments are used to measure different domains of quality of life of patients which were described below and represented in Fig. 18.1.

18.5

Physical Functioning

How much health limit for everyday physical activities such as walking, bending, kneeling, and running, lifting or carrying groceries, bathing or dressing, and climbing stairs.

300

A. N. Nagappa and S. Bhatt

Fig. 18.1 Quality-of-life (QOL) domains

18.6

Physical Role

How much difficulty is experienced with work or other regular activities as a result of physical health such as cutting down the amount of time spent on work or other activities, accomplished less than you would have liked, etc.

18.7

Bodily Pain

The amount of body pain experienced by the patient and how much did pain interfere with his normal work.

18.8

General Halt

An assessment of overall health is very good, good excellent, fair, and poor.

18.9

Vitality/Energy and Fatigue

The amount of energy and fatigue experienced by the patient.

18

Introduction to Pharmacoeconomics and Outcome Research

301

18.10 Social Functioning How much physical health or emotional problems limit the usual social activities like visiting families, friends, neighbors, relatives, etc.

18.11 Emotional Role How much personal or emotional problems show impact on usual daily work in the home and away from home (such as feeling depressed or anxious) as a result of cutting down the amount of time spent on work or other activities, accomplished less than you would have liked, etc.

18.12 Emotional Well-Being/Mental Health The degree to which the respondent is affected by emotional problems (such as feeling nerves, unhappy, depressed, or irritable).

18.13 Factors Affecting Quality of Life Factors affecting the quality of life such as advanced age, female gender, lower education level, low income, unemployment, comorbidities, poor control of the disease, lack of treatment options, adverse drug reactions (ADRs), ethnicity, and race are represented in Fig. 18.2 (https://www.who.int/chp/knowledge/publications/ adherence_full_report.pdf).

Fig. 18.2 SQOL factors

302

A. N. Nagappa and S. Bhatt

18.14 Applications of Quality-of-Life Instruments Wide application of quality-of-life measures has been found worldwide and represented in Fig. 18.3. 1. In daily medical practice, QOL instruments are used to assess the patient disease severity, response to treatment, and satisfaction with care or to improve the patient and healthcare provider’s communication. 2. To monitor the diseased course and response to therapy. 3. It will be useful for measuring the QOL of chronic illnesses. These illnesses include diabetes mellitus, osteoarthritis, gastrointestinal disorders, rheumatoid arthritis, chronic obstructive pulmonary disease, psoriasis, heart disease, posttraumatic stress disorder, and low back pain. 4. Quality-of-life instruments are used to determine the cost-effectiveness of two or more treatment options or diagnostic tests. It can help the healthcare providers to determine which treatment plan or diagnostic test is the best option therapy to improve healthcare through an evolutionary process. 5. Quality-of-life instruments are used in a cost-benefit analysis to make economic decisions about access to expensive drugs that may prolong life by a short amount of time and/or provide a minimal increase to quality of life. 6. Quality-of-life instruments are used in the final step in clinical trials of experimental therapies. Clinical trials depend on reliable and scientifically valid health outcome, measurements that are acknowledged and accepted by the Food and Drug Administration (FDA).

Fig. 18.3 Application of QOL instruments

18

Introduction to Pharmacoeconomics and Outcome Research

303

7. Quality-of-life instruments are used to interpret the quality-of-life outcomes among patients. 8. QOL research informs the individuals tasked with health rationalization or anyone involved in the decision-making process of agencies such as the FDA, European medicine agency, or National Institute for Health and Care Excellence.

18.15 Methods for Evaluation of Quality-of-Life Instruments Quality-of-life instruments can be evaluated by the following methods (https:// conjointly.com/kb/measurement-validity-types/):

18.15.1 Validity Content validity Construct validity Criterion validity

18.15.2 Reliability Test-retest Internal consistency Inter-interviewer reliability

18.15.3 Sensitivity to Change 18.15.3.1 Validity (https://conjointly. com/kb/measurement-validity-types/) In a degree of confidence that can place on inferences based on the scores from the scale.

18.15.4 Content Validity It refers to the degree to which an instrument contains a complete range of items with relevance to the disease under study. An instrument fails to measure attributes of health that are important to patients with the targeted disease. It will likely fail accurately to measure the respondents’ QOL. Although there is no gold standard to measure content validity, it may be subjectively evaluated by comparing the instrument to existing validated instruments, eliciting expert opinion regarding the item content, and pilot-testing the questionnaire in patients with the targeted disease (Halek et al. 2017).

304

A. N. Nagappa and S. Bhatt

18.15.5 Construct Validity It is the degree to which an instrument behaves as predicted when compared with existing patient-oriented and validated outcome measures (Louie et al. 2019).

18.15.6 Criterion Validity It is the extent to which the scores of a QOL instrument are related to a known gold standard measure of the same concept. In simple words, it is a test against a gold standard (Deshpande et al. 2011).

18.15.7 Reliability It is defined as the extent which produces the same results on repeated trials or measurements. In short, it is the stability or consistency of scores over time, for example, a weighing scale—one gets on it and read 150 as the weight—if one repeats it and gets the same weight each time, then the scale is reliable (https:// opentextbc.ca/researchmethods/chapter/reliability-and-validity-of-measurement/).

18.15.8 Test-Retest A test-retest method that involves administering the same measurement instruments to the same individuals under the same conditions after some period of time.

18.15.9 Internal Consistency (Homogeneity) It is a method to the consistency of results across items within a test. Internal consistency is estimated with half index and alpha (Cronbach) index.

18.15.10 Inter-Interviewer Reliability It determines the changes in the results when the instruments are administered by two or more interviewers. It is generally measured by person’s “r” value.

18.15.11 Sensitivity to Change The ability of an instrument is to detect the changes in the expected outcomes. The outcomes particularly important where subjective reports of health status are one of the primary outcomes of the trial. It can be detected via t-test, compares means at

18

Introduction to Pharmacoeconomics and Outcome Research

305

baseline and follow-up and Effect. It relates changes in mean score (form baseline to follow-up) to the standard deviation of baseline score (https://opentextbc.ca/ researchmethods/chapter/reliability-and-validity-of-measurement/).

18.15.12 Short Questions Define quality of life. Define health-related quality of life. What are the different factors influencing quality of life?

18.15.13 Long Questions Explain the different types of quality-of-life instruments with suitable examples. Explain the different domains for quality-of-life measures. What are the applications of quality-of-life instruments? What are the different evaluation methods for quality-of-life instruments?

18.16 Conclusion Pharmacoeconomics (PE) and outcome studies (OR) are coined together as health economics and outcome research (HEOR).These studies are the basis for health policy review and formulary selection of drugs. Pharmacoeconomics contains simple equations exploring the various facets of drug price and its impact on quality of life (QALY). On the other hand, HEOR studies focus on assessment of quality of life due to a treatment. Outcome research uses validated survey questionnaire which reveals the patient preference and helps in humanistic outcome. There are proposals to considering the humanistic outcome as an evidence for effectiveness of treatments.

References Ahmad A, Patel I, Parimilakrishnan S, Mohanta GP, Chung H, Chang J (2013) The role of pharmacoeconomics in current Indian healthcare system. J Res Pharm Pract 2(1):3–9 Committee on the Learning Health Care System in America; Institute of Medicine, Smith M, Saunders R, Stuckhardt L et al (2013) Engaging patients, families, and communities. In: Best care at lower cost: the path to continuously learning health care in America. National Academies Press, Washington Deshpande PR, Rajan S, Sudeepthi BL, Abdul Nazir CP (2011) Patient-reported outcomes: a new era in clinical research. Perspect Clin Res 2(4):137–144 Feingold KR 2000 Cholesterol lowering drugs. Feingold KR, Anawalt B, Boyce A, et al. South Dartmouth: MDText.com, Inc Franklin M, Lomas J, Walker S et al (2019) An educational review about using cost data for the purpose of cost-effectiveness analysis. Pharmacoeconomics 37:631–643

306

A. N. Nagappa and S. Bhatt

Halek M, Holle D, Bartholomeyczik S (2017) Development and evaluation of the content validity, practicability and feasibility of the innovative dementia-oriented assessment system for challenging behaviour in residents with dementia. BMC Health Serv Res 17:554 Hernlund E, Svedbom A, Ivergård M et al (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the international osteoporosis foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8(1):136. https://doi.org/10.1007/s11657013-0136-1 Institute of Medicine (US) Committee on Psychosocial Services to Cancer Patients/Families in a Community Setting, Adler NE, Page AEK (2008) Cancer care for the whole patient: meeting psychosocial health needs. In: The psychosocial needs of cancer patients. National Academies Press, Washington Institute of Medicine (US) Committee on the Consequences of Uninsurance (2002) Effects of health insurance on health. In: Care without coverage: too little, too late. National Academies Press, Washington Jo C (2014) Cost-of-illness studies: concepts, scopes, and methods. Clin Mol Hepatol 20(4): 327–337 Louie C, D'Agostino EN, Han D, Ryken TC (2019) Determining an appropriate outcome measure in neurosurgical research: investigating meaningful, valid, and practical metrics. Cureus 11(9): e5610 Robinson R (1993) Costs and cost-minimisation analysis. BMJ 307(6906):726–728 Roy V, Rana P (2018) Prescribing generics: all in a name. Indian J Med Res 147(5):442–444 Ryder HF, McDonough C, Tosteson AN, Lurie JD (2009) Decision analysis and cost-effectiveness analysis. Semin Spine Surg 21(4):216–222 Stergachis A (1995) Overview of cost-consequence modeling in outcomes research. Pharmacotherapy 15(5 Pt 2):40–42 Tunis SL (2009) A cost-effectiveness analysis to illustrate the impact of cost definitions on results, interpretations and comparability of pharmacoeconomic studies in the US. Pharmacoeconomics 27(9):735–744 Yousefi M, Assari Arani A, Sahabi B, Kazemnejad A, Fazaeli S (2014) Household health costs: direct, indirect and intangible. Iran J Public Health 43(2):202–209

Clinical Trials, Pharmacovigilance, and Drug Safety

19

A. N. Nagappa and Shvetank Bhatt

Abstract

Drugs are potentially useful in the treatment of disease and management of health. All drugs are bioactive and are capable of interacting with all cells and tissues. It causes many undesirable side effects causing serious problems to the patients. Some of the drug’s effects are capable of affecting the fetus causing illness in newborn. The governments have enacted several laws and regulations to ensure the safety of the public. Clinical trials and pharmacovigilance have become mandatory for drug approval for veterinary and human use. Clinical trials and pharmacovigilance are basis of evidence-based medicine and clinical practice. Keywords

RCT · Meta-analysis · Safety evaluation · Systematic review

19.1

Clinical Trials

Clinical trials are experiment that evaluates new drugs or new application of the drug and establishes the clinical efficacy and safety of these drugs by administering these drugs to human beings. Drugs are active molecules that originate from biological source, synthetic source, and mineral source. Drugs from chemical source seem to have reached saturation as drug discovery and development programs indicate slump in new molecules despite the necessity to discover and develop new molecular entity for the control and management of infectious diseases (https://www.nia.nih.gov/ health/what-are-clinical-trials-and-studies). A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_19

307

308

A. N. Nagappa and S. Bhatt

The time is running out of hand because many bacteria and other agents are showing microbial resistance. The super bug standing against all antibiotics is already an critical issue and small new molecules in the area of infectious diseases are not available, although much efforts have been put in drug discovery and development. The antibacterials are one of such examples. Moreover, now a days life style diseases such as diabetes and obesisty are becoming uncontrollable by the use of available marketed drugs. Untimely premature deaths have raised cause for concern among patients due to the failure to get new molecular entity in the management of lifestyle diseases. This has made the scientist to look for other sources like bio-therapeutic and mineral resources. A crisis of nonavailability of effective treatment is a big challenge for pharma industries and other stakeholders (Ventola 2015). Drug discovery and development in bio-therapeutics and drug delivery system have given sigh of relief for the pharma industries and other stakeholders. Drugs of biological source or different from conventional chemical drugs and its development pose different challenges which are under development. Hence, biological drug development is not only difficult but also time-consuming. Drugs from mineral source are looked down as poisonous substance and are not developed very much similar to herbal drugs. Any drugs to be used in humans should be proved as safe and effective by experimental proofs through in vitro, animal, and human studies (Differding 2017). In vitro and animal experiments are called preclinical studies, while experiments on human beings are called clinical studies. In vivo and animal experiment results cannot be extrapolated to human beings. There are a lot of differences in animal physiology and human physiology. The result of in vitro and animal experiments can be used to get a bird’s-eye view of its effect on human beings. It is highly unpredictable regarding safety issues and ADRs while administering to human beings; hence, drug regulators and the government should be highly alert and examine the data of drug development carefully before giving clearance for the next stage of drug development in human beings (Arora et al. 2011). Drug development in humans is divided into stages: phase one, phase two, phase three, and phase four. Further clinical studies are divided into primary research and secondary research.

19.2

Primary Research

19.2.1 Case Report/Case Series Case report study is an analysis in which a single patient is followed. It describes the treatment pattern and the outcomes of treatment. Such reports are available for inpatients while they are undergoing treatment in a hospital. Case reports are examined by doctor, nurse, and pharmacist who make their treatment process documented and are systematic in the format. It contains data of admission, mammographic details of the patients and doctor in charge, details of results of diagnostic

19

Clinical Trials, Pharmacovigilance, and Drug Safety

309

test conducted and medication given, and also a progressive chart of patient with parameters of basic life science like body temperature, blood pressure, and rate, height, and weight of the patient. Furthermore, there may be entries regarding probable diagnosis and confirmed diagnosis. It forms the basis for discharge summary and discharge medication. It is an active document which needs to be updated in which changes occur with treatment and patient conditions (Abu-Zidan et al. 2012).

19.2.2 Ecological Study Ecological studies are studies of risk-modifying factors on health or other outcomes based on populations defined either geographically or temporally. Both riskmodifying factors and outcomes are averaged for the populations in each geographical or temporal unit and then compared using standard statistical methods (Grant 2016).

19.2.3 Cross-Sectional Study In cross-sectional study, the relationship between disease and other variables of importance is examined in a defined population at a particular time. It is based on single-snap short study and does not have any follow-up data. This study reveals about the relationship between disease and factors affecting the disease conditions. For example, in diarrhea, if it is spread across the community, it becomes very important to examine its relationship with contamination of drinking water, nutrition status, and also electrolyte imbalance (Setia 2016).

19.2.4 Case-Control Study The case-control study is an observation study that begins with identification of a group of patients with disease and also individuals without the disease who are identical to the patients with a difference of people having no disease. Case-control study may be retrospective (backdate) and prospective (futuristic). The subjects are allocated to a case group if they show symptoms of disease or to a control group if they do not suffer from the disease. The relationship of risk factor to the disease is evaluated by determining how frequently risk factor is present in cases and controls. In case-control study, the intention is to reflect the rate of outcome in the population (retrospective analysis) when the two groups are retrospectively studied to identify any possible casual exposures. The relative risk of the outcome cannot be determined directly in the population. When incidence is not known (risk), then the relative risk is estimated by odds ratio (OR). Odds ratio (OR) of exposed among the disease is divided by odds ratio (OR) of not exposed; it has become evident when outcomes

310

A. N. Nagappa and S. Bhatt

with a relatively low prevalence odds ratio is a good method for estimating the relative risk (Lewallen and Courtright 1998).

19.2.5 Cohort Study Cohort study is a prospective study of individuals who are exposed and those who are not exposed to the suspected causal agent in a defined population. The cases and control are followed from the time of exposure. Incidences of the outcome are determined in both groups. The ratio of incidences in exposed group is divided by the ratio of incidence in nonexposed group. This is called relative risk or risk ratio (RR) for developing the outcome over time in a population (Song and Chung 2010).

19.2.6 Randomized Clinical Trial A clinical trial is experimentation on human being to establish safety and efficacy of a healthcare intervention. Healthcare intervention may be a new protocol or a new drug or may be both. In clinical trial, its objective is to lessen the severity and cure specific disease condition in human beings. Clinical study is a prospective study in which the effect and value of preventive/diagnostic/therapeutic intervention is compared in human beings under control (ideal) conditions. In clinical trials, there are at least two groups which are compared: the intervention group that receives the treatment, and the control group that does not receive any treatment in several clinical trials. Control group may receive either placebo or existing treatment. This has been necessary to minimize bias introduced by staff members, patients, or both. Randomized clinical trials are those in which allocation of the subjects is carried out in a random fashion. These are considered as golden standard in clinical trial as all care is taken to minimize bias during the conduct of the trial. The bias if present is going to lead to error in the outcomes of the result. The randomization is based on probabilistic rule which neither the investigator nor the patient can predict assignment of the patient to either interventional group or control group. Random assignment is helpful as it allows one to presume that all treatment arms contain subject with mostly equivalent characteristic and hence the major outcomes influenced by the intervention and not due to the differences in the individual subject (Doberer et al. 2021; Spieth et al. 2016).

19.3

Types of Randomized Clinical Trial

19.3.1 Mega-Trial Mega-trial is an RCT in which more than 10,000 patients are tested for outcomes of drug treatment or healthcare interventions. Due to a large number of subjects, the sponsors are able to identify and evaluate outcomes which are not possible to find

19

Clinical Trials, Pharmacovigilance, and Drug Safety

311

out. Typically mega-trial is involved in multicenter study sites and may also involve multiple countries and transcontinents. Although it is very expensive, it is beneficial to study the effect of drugs on a global population and also learn about rational differences of drug effects among different countries (Spieth et al. 2016).

19.3.2 Firm Trial The firm trial is an RCT in which subjects are allocated to investigational group and control group in a clinic or other institutional settings. In the firm trial, subjects are randomized to control clinic versus investigational clinical. The firm trial is different from normal RCT in which the control and the investigational group are within a single clinic. Advantages of a firm trial can give data which can reveal diversity in patient response in particular drug among different clinics (Cebul 1991).

19.3.3 Head-to-Head Comparison Study Head-to-head comparison study is an RCT wherein two different healthcare interventions are compared which have similar outcomes (Peyrin-Biroulet et al. 2017).

19.3.4 Equivalence Study Equivalence study is design to evaluate the outcomes of one healthcare intervention to another healthcare intervention in terms of safety and efficacy. The majors of equivalence study required are different from those required in trials trying to demonstrate the difference. The majors will vary greatly depending on whether the comparison is an attempt to show equivalent health (Nair 2019).

19.3.5 Nonrandomized Trial with Contemporaneous Controls Nonrandomized trial with contemporaneous controls is a trial in which the treatment group is compared with a similar cohort receiving care in the same setting by the same providers but not receiving the treatment within the same timeframe. A similar cohort is established by matching patients based on a set of demographic and clinical characteristic, age, sex, duration of disease, and concomitant diagnoses that may have an impact on the outcome being measured (Concato et al. 2000).

312

A. N. Nagappa and S. Bhatt

19.3.6 Nonrandomized Trial with Historical Controls Nonrandomized trial with historical controls is a comparison of the cohort receiving the intervention with a similar cohort that received care (but not the intervention being evaluated) in the same setting by the same providers, during another time period (usually earlier) (Concato et al. 2000).

19.4

Types of Clinical Trials

There are two main types of clinical trials: observational and interventional. In observational clinical trials, usually no drugs or treatment are involved. Researchers observe the patients by mentoring their health parameters over a period of time. The data generated is used in advancing understating of progression of a disease, for example, Parkinson disease and its treatment. In interventional clinical trial, the objective is to establish safety and efficacy of investigational new drug or therapy or experimental treatments. So among these broad categories, further it is classified as treatment trials, prevention trials, screening trials, quality-of-life trials, and genetic trials. The objective of treatment trials is to test treatments, drug combination, or surgical intervention to improve symptoms and/or slow down progression of disease. In preventions trials, the test approaches medicines, vitamins, mineral, vaccines, or lifestyle changes which can bring down the risk of developing a disease. Quality-of-life trials aim at finding out the intervention that improves comfort and quality of life or patients. The genetic trials aim at identifying an inherent risk of diseases in a population and identifying people at risk (https://www.cancer.org/ treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/ phases-of-clinical-trials.html).

19.5

Trial Phases

Clinical trials are conducted in series which are designated at phase one, phase two, phase three, and phase four. Phase one trials are the first to be conducted in human beings. Invitational new drug which is a potential therapy procedure is carried out with a goal to establish a new intervention safe for humans. Phase one trials are usually conducted on a small group of a healthy people ranging from 10 to 18. Apart from safety, phase one also aims to observe the side effects, effectiveness of route of administration, and appropriate doses of label. Phase two is conducted on patients ranging from 100 to 300 with an aim to evaluate safety and effectiveness in a larger group of patients. In this phase, instead of healthy individual, patients are utilized who are suffering from diseases for which the drug is likely to be used. In phase three trials, a large group of patients ranging from 1000 to 3000 are utilized to confirm the effectiveness of therapy and monitor side effects which are compared against standard treatment

19

Clinical Trials, Pharmacovigilance, and Drug Safety

313

already available. Phase three trials are usually conducted in multiple centers simultaneously. Evaluation in phase three is aimed to find out whether the treatment is going to benefit the patients. It is also important to make observations regarding the risk-benefit ratio of the treatment. Phase four clinical trial is conducted after the regulatory agencies have approved the treatment or the drug to be used among patients which means after the introduction of the drug in the market. This is also known as postmarketing surveillance or pharmacovigilance. Its aim is to identify any severe adverse drug reactions while in use by a large number of patients over a period of time. The responsibility of conducting phase four clinical trial and reporting to national pharmacovigilance program of India is on the pharma industries marketing that drug. These accumulated data become the bases of continuing or banning of the product. Phase four clinical trial can bring out additional pharmacological activities of the drug. Pharmacological activities may lead to the new use of drug. Doctors may observe new pharmacological activities which can be converted into new therapeutic application, for example, sildenafil is a drug used for erectile dysfunction; however, while in use by patients, doctors observed it can bring down blood pressure in the pulmonary artery. Hence, it is found useful in the treatment of pulmonary arterial hypertension. It is also found useful as a treatment of angina pectoris, a symptom of ischemic heart disease (https://www.cancer.org/treatment/ treatments-and-side-effects/clinical-trials/what-you-need-to-know/phases-of-clini cal-trials.html).

19.6

Secondary Research

19.6.1 Systematic Review Systematic review is a secondary research in which already published clinical data is reviewed to establish an evidence for a particular clinical question. There is a huge clinical data available for access and review. This clinical data gets updated in a continuous manner, and it is difficult to comprehend and use it as an evidence to make a rational decision. Systematic review is most useful where there is a substantial research question or several empirical studies have been published and there are uncertainties about the result. There are two types of systematic review which can be either international (RCT) or observational (case control or cohort). Systematic review compiles all empirical evidence that fit prespecified eligibility criteria in order to answer a specific research question. In a systematic review, its objectives with predefined eligibility criteria stated there shall be a categorical reproducible methodology. There will be a throw such that it attempts to identify relevant studies. It is also important to know whether the risk of bias is also included. For example, assessment of the validity of findings is also included. The syntheses of the evidence characteristic of finding are also part of the systematic review. It is important to note that in the era of consumer rights, the clinical information available may in the format of narrative, which may not be very critical. It is observed in several instances it is not updated. The available literature may be biased due to

314

A. N. Nagappa and S. Bhatt

opinion of practicing doctors; however, the published opinion cannot be used directly as it is available in the raw form. It may also happen so different reviewers might have reached different conclusions about the treatment. It is also possible to have a bias depending on subspecialty of reviewer. In a narrative review, there can be little scope and effect to discuss heterogeneity in the literature (Uman 2011). Systemic review is beneficial as it brings the evidence in the support of therapy. For example weather to use clot busters or beta blockers in the treatment of heart attacks. Systematic reviews came into prominence in the mid-1970s. However, it was not used in clinical practice till the 1990s. Systematic reviews are also applied to secure grand funding for research and also may be part of dissertation or postgraduate thesis. It also helps in identifying future research agenda. It is also useful in establishing the clinical or cost-effectiveness of a treatment. Also, it establishes feasibility of intervention and allows the information to be assimilated quickly and easily as the cryptic information is translated into a simple quantifiable data. The dilemma of clinical practice gets cleared, hence lessening confusion (Uman 2011).

19.6.2 Limitation of Systematic Review Due to variability of quality of systematic review, it becomes difficult to accept the result and use it in clinical practice without analysis. Systematic review becomes redundant if not updated regularly. It is also observed that many systematic reviews become out of date by the time they get published. The major limitation of systematic reviews may exclude non-English research publications. It may also get diluted by gray literature and also may exclude early literature. The quality assessment can still be vary by subject opinions of the reviewer. Despite the above limitation, still systematic reviews are needed because it addresses and obtains a good answer to important clinical question by using earlier published evidence. It is the summary of several primary clinical trials. It compares the outcomes of several clinical trials and use the visual output (forest plot). A forest plot, also known as a blobbogram, is a graphical display of estimated results from a number of scientific studies addressing the same question, along with the overall results. It eliminates uncertainty of care provider about evidence of treatment. Systematic review can be about intervention by doing systematic review with RCT. In observational systematic reviews, one can do with birth rate and IQ and mortality of women’s health and morbidity. Literature review is different from systematic review which aims at summarization of specific topic or literature review is a nonquantitative summary of published literature. A systematic review is a quantitative summary which has preset criteria with a protocol. Meta-analysis is a combination of systematic literature review and quantitative synthesis of findings from multiple studies. A literature review is a type of study generally performed to provide a brief overview of published literature. A systematic review has two major differences from literature review. In systematic review, there is a formal and compressive search for a relevant literature. This generally includes database such as MEDLINE,

19

Clinical Trials, Pharmacovigilance, and Drug Safety

315

PMC, and other important databases of the particular topic. Systematic review also further scrutinizes the cross-references from the studies which were considered. Further there are explicit, objective criteria for selecting studies to be included, for example, the criteria which spells out inclusion and/or exclusion, and exclusion criteria shall be strictly followed. These criteria are generally set prior to the writing of systematic review. Further systematic review also evaluates the quality of reviewed literature (Banerjee and Argaez 2017).

19.6.3 Meta-Analysis Meta-analysis involves both a systematic review and a quantitative combination of results across similar studies. Meta-analysis generally performed are published studies. However, they may also include results from unpublished studies. Inclusion of unpublished studies may affect the quality of meta-analysis in a negative manner. It is better to depend on published studies which are peer-reviewed. Meta-analysis methodology for combining studies can be of two types: one is fixed effects, and the other is random effects. Fixed effects indicate that the results of the analysis are conditional on population of the included studies. Random effects assume that the study’s results reflect the outcomes of a broader population. Meta-analysis is useful in order to increase statistical power available to and intervention effect on key outcomes and also get an idea about the size of the population to which outcomes can be applied. Results of meta-analysis are used to assess the effectiveness of a healthcare product or healthcare service. It also gives clues and paves way for new studies. Meta-analysis can bring out the cases wherein the existing literature is composed primarily of small cohort studies with conflict results. Hence, it is agreed that meta-analysis provides the quantitative summary more accurately from a body of literature. Traditionally, meta-analysis is used to combine data on clinical outcomes like efficacy mortality rates of adverse events across studies. It can also be used in economic and QOL outcomes in a robust manner. Further, one can also incorporate study quality as a parameter into a meta-analysis by using a predefined objective. It yields quality scoring system and certifying studies based on the scores. It is important to be careful while including studies in a systematic review and metaanalysis. One should have robust criteria of selecting studies for systematic review and meta-analysis. It is usually found that reviewers are confused whether they are measuring the quality of the research or quality of writing of the manuscript. Another problem faced by the reviewers is deciding the authenticity of original research and separating it from duplicate and overlap studies. It is found that one paper appears in literature in many forms and also verbatim copies with minor modification or same studies with a different outcome (Uman 2011).

316

19.7

A. N. Nagappa and S. Bhatt

Pharmacovigilance and Drug Safety

In recent times, the public have become sensitive to the drug-inflicted injuries and are very much concerned about it. The drug-inflicted injuries comprise of organ damage to the user and genetic aberrations to the next generations. It is very much important to identify the adverse drug reactions before it causes harm to a large number of patients. Following World War II, the great Industrial Revolution spurred. The development in science and technology heralded the era of modern living and management of health and other social needs. Especially in the Europe there were many industry setup with actively involved commercial industry practices. The epidemic of diseases started hunting the mankind in order to control the suffering and death. There was a need of new drugs. Hence, the drug discovery and research became a prominent activity. Furthermore, in order to sponsor these activities, commercialization of drugs and health services was developed to support the sustained activities. Many new molecular entities were synthesized, for example, sulfa drugs, arsenic compounds, and various antibiotics like streptomycin, tetracycline, etc. One of the biggest questions was regarding safety of these drugs in human when used for treating diseases. The first thought is to establish the safety of new drugs in animals. Various animal models were established to test the safety of these drugs. Ultimately, it led to the establishment of therapeutic index which consisted of efficacy and toxicity. There were many adverse drug reactions (ADRs) mandating the necessity of vigilance of long-term safety issues of the drugs in the humans. The course of long-term usage was soon realized that many of these drugs manifested a variety of ADRs not only in the people who use them but also in children born to them, for example, thalidomide-induced teratogenicity (Jeetu and Anusha 2010). The governments, regulators, and public learned a hard lesson, that safe-looking drugs are not so safe and are capable of causing genetic injuries and cancers. Watching and keeping an eye over the ADRs of drugs became a mandatory activity insisted by the government and drug regulatory agencies. The Pharmacovigilance Programme of India (PvPI) was started by the Government of India (GOI) on 14 July 2010 with the All India Institute of Medical Sciences (AIIMS), New Delhi, as the national coordination center for monitoring adverse drug reactions (ADRs) in the country to safeguard public health. The Government of India begins pharmacovigilance activity in the Department of Pharmacology in AIIMS, New Delhi, decades ago. However, this activity persuaded an academic documentation. Hence, it has remained isolated among academic circles. In the last decades, the GOI took keen interest and made a series of rules and regulations with an objective of serious monitoring of ADR profiles of used prescription drugs. The GOI established the National Pharmacovigilance Programme of India (PVPI) Centre and handed over the responsibility to the Central Drugs Standard Control Organization (CDSCO).

19

Clinical Trials, Pharmacovigilance, and Drug Safety

317

Table 19.1 Therapeutic drugs causing serious hazards to the public health (https://www.who.int/ medicines/areas/quality_safety/safety_efficacy/Pharmacovigilance_B.pdf) S. no. 1 2

3 4

Drugs Immunoprin (thalidomide) Brufen (ibuprofen) Grepafloxacin (raxar) Indoprofen (indomethacin)

5

Butazolidine (phenylbutazone)

6

Toradol (ketorolac)

7

Vioxx (rofecoxib)

8

Bextra (valdecoxib)

9

Permax (pergolide) Nimulid (nimesulide)

10

Therapeutic category Immunomodulator Nonsteroidal antiinflammatory drug (NSAID) Fluoroquinolones Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Nonsteroidal antiinflammatory drug (NSAID) Dopamine receptor agonist Nonsteroidal antiinflammatory drug (NSAID)

Type of toxicity Teratogenicity, multiple myeloma Hepatotoxicity, jaundice

Year withdrawn 1961 1968

Cardiac repolarization, QT interval prolongation Gastrointestinal bleeding

1999

Off-label abuse, hematologic toxicity

1985

Hemorrhage, renal failure

1993

Myocardial infarction and stroke

2004

Stevens-Johnson syndrome

2005

Heart valve damage

2007

Hepatotoxicity

2011

1983

Table 19.2 Drug-induced toxicity (Guengerich 2011) S. no. 1 2 3 4 6 7 8 9 10 11

Drugs Abacavir Acetazolamide Aminoglycoside Angiotensin-converting enzyme inhibitors Amphetamine Chloroquine Dexamethasone Doxorubicin Methotrexate Ximelagatran

Toxicity Myelotoxicity Myelotoxicity Nephrotoxicity Nephrotoxicity Neurotoxicity Methemoglobinemia Osteoporosis Aplastic anemia Neurotoxicity Hepatotoxicity

Therapeutic drug-causing serious hazards and drug-induced toxicities are summarized in Tables 19.1 and 19.2.

318

19.8

A. N. Nagappa and S. Bhatt

Conclusion

Clinical research is needed to answer and resolve the problem posed by therapeutic agent not only during drug development but also during clinical practice. The errors in clinical research and practice sometime mislead the therapeutic team leading to many historical incidents of drugs that cause serious problems to the public. It has become the responsibility of the drug regulator to monitor and review the data of clinical trials and pharmacovigilance submitted by the manufacturer in support of drug safety and efficacy.

References Abu-Zidan FM, Abbas AK, Hefny AF (2012) Clinical “case series”: a concept analysis. Afr Health Sci 12(4):557–562 Arora T, Mehta AK, Joshi V et al (2011) Substitute of animals in drug research: an approach towards fulfillment of 4R's. Indian J Pharm Sci 73(1):1–6 Banerjee S, Argaez C (2017) Strengths and limitations of systematic reviews and meta-analyses using AMSTAR. In: Eye movement desensitization and reprocessing for depression, anxiety, and post-traumatic stress disorder: a review of clinical effectiveness. Canadian Agency for Drugs and Technologies in Health, Ottawa Cebul RD (1991) Randomized, controlled trials using the metro firm system. Med Care 29(7 Suppl):JS9–J18 Concato J, Shah N, Horwitz RI (2000) Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342(25):1887–1892 Differding E (2017) The drug discovery and development industry in India-two decades of proprietary small-molecule R & D. ChemMedChem 12(11):786–818 Doberer K, Duerr M, Halloran PF, Eskandary F, Budde K, Regele H, Reeve J, Borski A, Kozakowski N, Reindl-Schwaighofer R, Waiser J, Lachmann N, Schranz S, Firbas C, Mühlbacher J, Gelbenegger G, Perkmann T, Wahrmann M, Kainz A, Ristl R, Halleck F, Bond G, Chong E, Jilma B, Böhmig GA (2021) A randomized Clinical trial of anti-IL-6 antibody Clazakizumab in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol 32(3):708–722 Grant WB (2016) The role of geographical ecological studies in identifying diseases linked to UVB exposure and/or vitamin D. Dermatoendocrinol 8(1):e1137400 Guengerich FP (2011) Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metab Pharmacokinet 26(1):3–14. https://doi.org/10.2133/dmpk.dmpk-10-rv-062 Jeetu G, Anusha G (2010) Pharmacovigilance: a worldwide master key for drug safety monitoring. J Young Pharm 2(3):315–320 Lewallen S, Courtright P (1998) Epidemiology in practice: case-control studies. Commun Eye Health 11(28):57–58 Nair B (2019) Clinical trial designs. Indian Dermatol Online J 10(2):193–201. https://doi.org/10. 4103/idoj.IDOJ_475_18 Peyrin-Biroulet L, Lopez A, Sandborn W (2017) Head-to-head comparative studies: challenges and opportunities? J Crohn's Colitis 11:567–575 Setia MS (2016) Methodology series module 3: cross-sectional studies. Indian J Dermatol 61(3): 261–264

19

Clinical Trials, Pharmacovigilance, and Drug Safety

319

Song JW, Chung KC (2010) Observational studies: cohort and case-control studies. Plast Reconstr Surg 126(6):2234–2242 Spieth PM, Kubasch AS, Penzlin AI, Illigens BM, Barlinn K, Siepmann T (2016) Randomized controlled trials - a matter of design. Neuropsychiatr Dis Treat 12:1341–1349 Uman LS (2011) Systematic reviews and meta-analyses. J Can Acad Child Adolesc Psychiatry 20(1):57–59 Ventola CL (2015) The antibiotic resistance crisis: part 1: causes and threats. P T 40(4):277–283

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical Trials (RCT)

20

A. N. Nagappa and Shvetank Bhatt

Abstract

The questioning of rationality in drug prescription was the beginning of evidencebased medicine. The extensive promotion of medicine by pharmaceutical industry has led to the widespread irrational use of medicines especially when regulatory authorities are weak. The availability of digital products supporting evidence-based medicine has simplified the process of practice. Advances in RCT, meta-analysis (MA), and systematic review are increasingly used in clinical practice. The Network MA helps one to use online data for clinical practice and research. Keywords

Forest plot · Meta-analysis · EBM · Systematic review

Patients and health consumers have the habit of visiting the healthcare facilities whenever they fall ill. In order to mitigate the suffering due to diseases, they usually prefer to consult community pharmacist or nurse and seek opinion and medicines. A patient also asks pharmacist or nurse whether they should visit a doctor. In the above choices, the pharmacist/nurse should be able to assess the patient’s condition as minor ailment or major diseases. Pharmacist with their clinical assessment is able to guide the patient whether over-the-counter (OTC) medications shall be sufficient or else they must visit a doctor immediately for proper diagnosis and treatment (Bennadi 2013). Patients are advised to see a doctor and shall go to a doctor for proper diagnosis and evaluation. Doctor starts with various assessments of health A. N. Nagappa · S. Bhatt (*) Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India e-mail: [email protected] # The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. N. Nagappa et al. (eds.), Perspectives in Pharmacy Practice, https://doi.org/10.1007/978-981-16-9213-0_20

321

322

A. N. Nagappa and S. Bhatt

like physical condition quickly assessing the vital signs like BP, pulse rate, heart rate, and respiration rate to ensure the patient is not heading toward a serious condition. Doctor assesses the patient with several signs and symptoms to arrive at an empirical decision regarding the patient conditions. The patient should undergo various recommended diagnostic tests in order to get a clear picture of health and also evidence regarding the diseases in patients (World Health Organization 2012). In order to give an immediate relief to the patients from the suffering of the disease, the doctor may prescribe medicines for symptomatic relief. Usually if the fever and the pain are the symptoms, paracetamol is prescribed. If the patient is having cough/ cold, patient may be prescribed with chlorpheniramine. In case of hyperacidity, patient may be advised to take antacids or ranitidine a H2 blocker. The idea is to make patients relieved from bothering signs and symptoms. Patients are asked to visit again with results of diagnostic test undertaken. The doctor even after going through the lab reports might not have clear-cut evidence for treatment of the conditions (Morice et al. 2006). In case of malaria and typhoid, the signs and symptoms appear very similar making the diagnosis confusing based on physical examination of the patients. The doctors usually resort to prescribing medicines mostly empirically through a guess diagnosis. The empirical treatments are the most popular approach among doctors and are practiced widely. The empirical treatments are based on individual experience and skills. It does not take much time for an experienced doctor to guess what is happening to patient. The medical sciences have been updated and an intelligent doctor shall be able to understand about the disease by his skills which were acquired through years of experience (Masic et al. 2008). The patients are in a great hurry. They are very much demanding for quick fix solutions for their health conditions. They are not interested what will happen to them after 3 or 5 years by consuming drugs in an irrational manner. It is due to the government and regulatory visionary policies that do not wish the public should not be harmed due to drugs in a long run. The GOI has launched the PvPI and kept a control over the pharmaceutical industry for regulating prescription habits of the doctors. The government is bringing out series of reforming amendments in Indian Medical Council Act, which is called as Health Authority of India. The development in therapeutics and information technology have made it possible to provide evidence-based treatments/medicine in place of empirical method. Evidence-based medicine (EBM) is the careful, clear, cautious, and rational use of current medicine, the best evidence in processing decisions with respect to the care of individual patients. EBM integrates experience in clinics and patient values with the best available updated information of research. While treating infections of bacterial origin in an empirical approach, antibiotics are prescribed based on sign and symptoms of disease condition, wherein EBM is on the identification, isolation of infected bacteria, and determining the cultural sensitivity of infected bacteria. It is also the basis of selection of antibiotic. Pharmaceutical care is affected by the availability of the evidences and quality of evidence. Pharmacists should have an adequate understanding about how to use the

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical. . .

323

evidence results from studies. However, many pharmacists feel difficulty in understanding and interpreting the related statistics. Furthermore, depending on the level of research and its applicability, the rational practice needs to be acquired as a skill in providing pharmaceutical care. The success of pharmaceutical care depends upon the quality of clinical evidence, process of using evidences in practice, and understanding barriers in using evidences. Evidence-based medicine was introduced to PubMed in 1997 as a medical subject heading. It was coined as a method of practice medicine with the aim to benefit the patients and evaluate their symptoms to take care. It requires the careful combination of best evidence of research with the value of patients to make decision about medical care. Generally, MA is considered as the best-quality evidences in pharmacy followed by systematic reviews, randomized controlled trials, and nonrandomized controlled trials. This model is the general case. But there are exceptions where reviews are not available and trials are not possible; in that case, observational studies or case series shall become the best-quality evidence available (Masic et al. 2008).

20.1 1. 2. 3. 4. 5. 6. 7. 8. 9.

Steps of Meta-Analysis (MA)

Formulating research question Developing a proposal Comprehensive literature search Selection of study Critical appraisal of study Extraction of data Synthesis of data Sensitivity and subgroup analysis if appropriate and possible Preparing a structure report

20.2

Meta-Analysis (MA)

MA is a measurable, proper, epidemiological study design used to assess the outputs of previous research data systematically to find out decisions about the body of research. Mostly, but not obligatory, the study is based on randomized, controlled clinical trials. Most of the researchers agree that MA provides better quality evidence than other methods of generating it. MA is performed with careful selection of randomized controlled trials using inclusion and exclusion criteria. This procedure of screening out removes unacceptable methodological bias. It also uses complex statistical methodology and recalculates the results in the selected studies. Ultimately the results and interpretation should be reproducible with least errors. The results produced in MA are more generalizable than by one original large trial (http:// medtrain.chm.msu.edu/ebm/Meta-analysis/steps_meta.html). The forest plot (FP) is an important method via which researchers can summarize data from various sources in one image. Graphical depictions of the MA are known

324

A. N. Nagappa and S. Bhatt

as FP. The word devised from the idea that graph had a forest of lines. In the early 1980s, the plot was originated; however, the term FP was used in 1996. In the year 1998, modern form of FP was originated. It becomes very difficult to evaluate a lot of different papers that ask the same question. This is exclusively true if the articles analyzed come to diverse decisions and have different statistical parameters either in favor or against a conclusion. An FP includes all the significant and relevant studies asking the same question, detects a common statistic in the said papers, and presents them on a single set of axis. Doing this allows you to compare straightforwardly, what the studies show and the result quality all in one place (http://medtrain.chm. msu.edu/ebm/Meta-analysis/steps_meta.html).

20.3

Fundamentals of Forest Plot (FP)/Blobbogram

An FP is well-known as a blobbogram (Figs. 20.1 and 20.2). It is a graphical representation of obtained results from numerous scientific studies addressing the same question, together with the overall results. In FP, the horizontal axis usually represents the statistic the studies being profiled show. This could either be a “relative” statistic like an odds ratio (OR) or a relative risk (RR). Or the statistics being used might be an “absolute” one such as absolute risk reduction (ARR) or standardized mean difference (SMD). Knowing the dissimilarities between relative and absolute statistics is crucial because it influences which number comes on the vertical line. The vertical line is recognized as the “line of null effect.” This line is placed at the value where (as the title suggests) there is no relation between an exposure and outcome or no dissimilarity between two interventions. If you recall from your statistics classes, relative statistics such as OR or RR have a null effect

Fig. 20.1 Forest plot (blobbogram)

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical. . .

325

Fig. 20.2 Combining all the studies of the forest plot

value of 1. For absolute statistics like absolute risk or ARR or SMD, the null difference value is 0. Hence, why the value at the line of no effect is relevant to the statistic being used (https://artsandculture.google.com/entity/forest-plot/m02rb0 lz?hl¼en). The horizontal axis normally denotes the statistic of the studies being profiled show. This could be either a “relative” statistic like an odds ratio (OR) or a relative risk (RR). Or the statistics being used might be an “absolute” one such as absolute risk reduction (ARR) or standardized mean difference (SMD). Knowing the variance between relative and absolute statistics is crucial because it decides which number sits at the vertical line. A point estimate of the result of the study is demonstrated by a black box. This black box also shows a representation of the study size. The bigger box represents more participants in the study. A horizontal line explains the 95% confidence interval (CI) boundaries. What each side of the null effect line demonstrates (i.e., if it supports the control or the intervention) is also critical when viewing at the individual studies. This will be dissimilar and depend on the question that you have asked for your studies. For instance, if you are searching at the risk between an exposure and an outcome, what each side of the vertical line demonstrates will be different to an instance where you are paralleling an intervention with a control. Helpfully, for most FPs published today, the authors helpfully mark what each side of the line demonstrates. If it isn’t marked, recollect every time to go back to first principles of the statistic you are utilizing. The horizontal line and whether it crosses the “line of null effect” is quite crucial to take note of for each and every study. If you recall, the amazingly basic definition of the 95% CI is “The range of values within which you can be 95% certain the true value lies.” If the horizontal line crosses the line of null effect, what that is efficiently saying is that the null value stays within your CI and hence could be the true value. If I was breaking this down to its most obvious explanation: “any study line which crosses the line of null effect does not illustrate a statistically marked result.” Moreover, it is not guaranteed, as a rule of

326

A. N. Nagappa and S. Bhatt

thumb, the studies with a greater number of participants or patients typically have a narrower CI and hence a smaller horizontal line. So in essential terms: 1. The bigger the study, the smaller the horizontal line and the bigger the black box demonstrating the point estimate. This means there are less possibilities for those studies to cross the line of null effect. Why? As your 95% CI should have a much smaller range. 2. The smaller the study, the wider the horizontal line and the smaller the black box representing the point estimate. This means it is more obvious for those studies to cross the line of null effect (because your 95% CI will be much bigger) (https:// dbpedia.org/page/Forest_plot). Now that you have gone through the above description, have a glance at study (a) and study (b) on Fig. 20.1. Add two more studies at the top (have a go at interpreting them) as well as a diamond. Now, the diamond is probably the most critical thing you will observe on a FP. The diamond demonstrates the point estimate and CI when you combine and average all the individual studies together. If you drew a vertical line through the vertical points of the diamond, that demonstrates the point estimates of the averaged studies. The horizontal points of the diamond demonstrate the 95% CI of this combined point estimate. If you remember what I said in part 2 about the size of the CI, because this combined value effectively groups each and every participant from all the individual studies, the CI range for this result should be the smallest on the FP (and in 99% of cases it normally is). The directions about crossing the line of null effect are still true here: if the horizontal tips of the diamond cross the vertical line, the combined result is potentially not statistically significant. Why? If you recall, if the 95% CI holds the null value, you cannot be certain that the null value isn’t the true value (https://dbpedia.org/page/Forest_plot).

20.4

Bringing it All Together

So we have talked about a number of the elements of the FP itself. Let’s have a bit of a look at all the “bumf” so to speak that sits around the FP on the graph. Let’s go back to our original image. Figures 20.1 and 20.2 highlight different elements on the FP that are worth noting.

20.5

To Summarize What Is Covered

1. Each horizontal line on an FP demonstrates an individual study with the result plotted as a box, and the 95% CI of the result displayed as the line. 2. The implication of each study falling on one side of the vertical line or the other depends on the statistic being used.

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical. . .

327

3. If the individual study crosses the vertical line, it means the null value lies within the 95% CI. This implies the study result is in fact the null value and therefore the study did not observe a statistically significant difference between the treatment and control groups. 4. The diamond at the bottom of the FP shows the result when all the individual studies are combined together and averaged. The horizontal points of the diamond are the limits of the 95% CI and are subject to the same interpretation as any of other individual studies on the plot. 5. The I2 statistic gives you an idea of the heterogeneity of the studies, i.e., how consistent they are. If the I2 value is >50%, it might mean the studies are inconsistent due to a reason other than chance. This might make the conclusions you draw from the FP questionable. Systematic reviews: Systematic reviews are again peer reviews like MA, but without complex statistical treatment. A comprehensive literature search will be done to answer a particular clinical issue. A large number of articles are reviewed, and the results are summarized in a logical order. Cochrane collaboration which is considered as a center of EBM gives systematic reviews and MA on many clinical topics. Clinical guidelines and protocols are summarized and shortened article guides based on mostly the systematic reviews and MA. MA, systematic reviews, and clinical guidelines become tertiary sources of information in providing pharmaceutical care (Uman 2011). Randomized controlled clinical trials: Randomized controlled trials (RCTs) are considered as gold standard clinical study designs. MA and systematic reviews are primarily done on RTCs. Thus, RTCs become primary sources of information which is firsthand or called as original research from which review research is done to make it more practice-related or user-friendly in MA or systematic reviews. RCTs are generally costly and time-consuming as they are very experimental and prospective. Care is taken to avoid the influences of confounding factors, and blinding is done to avoid personal bias. Though RCTs are the highest level of scientific study designs, they involve high levels of ethical issues. Even though the results are more reproducible, they are not naturally as it will be obtained in observational studies discussed below. Naturally means, in real practice setup, there are many other influencing factors (confounder) in reality, so the results obtained in RTCs are seldom observed in real practice. But as a piece of information, RTC produced more standard information than observational studies (Kabisch et al. 2011). Cohort studies: Cohort studies are observational, i.e., not very experimental. Large study populations are observed in the real practice setup over a period of time to find out if a particular agent or a condition results in certain clinical outcome. Cohorts are not costly as RTCs, and there are considerably lesser ethical concerns in general. But the results are not generalizable as of RTCs as they are highly dependent on the practices and other related factors in that study setup; when it changes, there are possibility of changes in results. Cohort means a defined group of people with certain clinical characteristics. There will be a control group who differs from the cohorts. And the study design could be mostly prospective or sometimes

328

A. N. Nagappa and S. Bhatt

retrospective. Prospective studies are generally expensive than retrospective studies (Song and Chung 2010). Case-control studies: Case-control studies are another type of observation designs which are retrospective in nature. Here the study focuses on certain outcomes which have happened and look back what factor or condition causes it. They are cheap and could be finished in less time by using medical record and/or databases. But always system lacks completeness of information recorded. So retrospective designs could be more biased as it is not possible to screen the exposures with an exhaustion inclusion and exclusion back in history (Song and Chung 2010). Case series: Case studies are generally not considered as a good study design as it is very subjective and the results shall not be the same in another patient. But in case of rare incidences, where an RTC or observational study is not possible, couple of cases (case serious) of similar kind provides valuable information. Especially in case of rare and serious adverse drug reaction, case reports have high value in clinical decision-making (Mathes and Pieper 2017). Editorials and expert opinions: Certain studies are not possible due to ethical or practical reason. In that case, an expert opinion holds importance in practice. Also it is well known that in evidence-based practice, expert opinion need to be combined to produce the best care by considering local clinical experiences. Animal studies: One of the pharmaceutical care areas where animal research results are widely use is of pregnancy risk of new medicines. Animal toxicology results are also of certain value as human toxicological studies are relatively unethical. So still we use some animal study results in clinical practices, even though its scientific value is limited (Akhtar 2015).

20.6

Process of Using Evidences in Practice

The process of practicing evidence-based pharmaceutical care could be listed into the following steps: (a) (b) (c) (d) (e) (f) (g)

Asking practical questions Finding suitable evidence Categorizing level of evidence Critical appraisal Decision-making Communication and monitoring the outcomes Asking practical question

The question needs to be not only theoretical but also practical. It has to be answered in a stipulated time with an acceptable solution.

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical. . .

329

20.6.1 PICO Model In a simple way, we can say how evidence-based pharmaceutical care is practiced by formulating a clinical question and answering it. One of the best models to formulate a clinical question is PICO (patient, intervention, comparison, outcome): P: Patience or population I: (Pharmaceutical care) Intervention C: Comparison with alternative interventions O: (Expected) Outcome For example, if a pharmacist has to find out which oral hypoglycemic agent works well for diabetes patient in old age with a lower risk of hypoglycemia. After ruling out the intolerances, the pharmacist could develop PICO model for the patient: P ¼ geriatric patient with diabetes, I ¼ Glibenclamide, C ¼ glipizide, and O ¼ lower body sugar level. A review research or original research could be started based on a clinical question developed using PICO model (Aslam and Emmanuel 2010).

20.7

Finding Suitable Evidence

There are a couple of evidence-based database and tools which help collect more user-friendly evidences. Some of the examples are Cochrane Library, National Institute for Health and Care Excellence, National Library of Medicine, National Guideline Clearinghouse, TRIP database, ACP Journal Club, Clinical Evidence, Essential Evidence Plus, Micromedex, Lexi-Comp, Iowa Drug Information System, etc. Some of the secondary sources of information which do abstracting and indexing services help in screening the articles. Some of the examples are PubMed, Embase, Scopus, Directory of Open Access Journals, Web of Knowledge, etc. (https://med. mercer.edu/library/database-differences.htm). There can be a set of standard journals read periodically which believed to have a good peer-review process and has a priority in publishing articles which could influence the current pharmacy practice.

20.8

Categorizing Level of Evidence

The Oxford Centre for Evidence-Based Medicine (OCEBM) levels of evidence were developed by an international group with periodic reviews. It could be used along with critical appraisal in categorizing the quality of evidences. Note: Users can add a minus sign “–” to denote the level of that fails to provide a conclusive answer because:

330

A. N. Nagappa and S. Bhatt

20.9 (a) (b) (c) (d)

Grades of Recommendation

Consistent level 1 studies Consistent level 2 or 3 studies or extrapolations from level 1 studies Level 4 studies or extrapolations from level 2 or 3 studies Level 5 evidence or troublingly inconsistent or inconclusive studies of any level

(Adopted from the Centre for Evidence-Based Medicine: http://www.cebm.net/)

20.10 Critical Appraisal Critical appraisal is the skill used in evaluation evidences in clinical literature. There are a huge number of articles published around the globe. Screening and selecting well-designed and well-written studies would be tough. It is better to depend on MA, systematic reviews, and clinical guidelines in a busy practice. Using pharmaceutical care guidelines developed by the American Pharmacists Association, American Society for Health-System Pharmacist, etc. could help (Al-Jundi and Sakka 2017). If there is time to evaluate the published studies, then we have to look at the clarity of research question, study setup, study population and size, inclusion and exclusion criteria, methodological designs, statistical tool used, and interpretation of the result. CAT maker is a software tool which helps in making critically appraised topic (CAT) for the selected article based on a clinical question. Different databases and computer-based tool made this process of evaluating literature more efficient (Brennan et al. 2020).

20.11 Decision-Making Once the reliable study is identified, the next question is how suitable it is our patient. How to and up to what extent we could use the information in our practice need to be answered. We did discuss earlier that an RTC is the best scientific study design, but it is performed in an experimental study. The pharmaceutical care plan which is prepared for a particular patient shall fall under same category but with considerable real-life differences. Most of the time evidences available is raw and could not be used directly in the patient. Understanding relative risk, relative risk reduction, absolute risk reduction, number needed to treat, etc. will help in making a better clinical decision. Assessment of satisfaction such as CI, probability, kappa, and power of the study is important in forecasting suitability of the study for the patient under care (Houle 2015).

20

RCT, Systematic Reviews, and Evidence-Based Medicine: Randomized Clinical. . .

331

20.12 Communication and Monitoring the Outcomes In clinical pharmaceutical care practices, we have to communicate the care plans to physicians, nurses, and patients. In community pharmaceutical care practice, most of the time, it would be sufficient to communicate to the patient alone. In any case, one of the best methods is to prepare the points in brief (preferably one or two pages) and give it in print. We had seen the limitations of using evidences for the benefits of a particular patient in certain situation. It is imperative to monitor the clinical outcome due to the care strategy. If the desired outcome is not achieved, it shall become essential to modify or change the care plan or its implementation to produce better clinical outcomes at the earliest (McDonough and Bennett 2006).

20.13 Barriers in Evidence-Based Pharmaceutical Care The use of evidence-based practice in pharmaceutical care or even in medicines has been a slow process. There are many barriers for adopting evidence-based practices especially in a resource-limited setting. Most of the high-quality evidences are costly and not affordable by most of the developing or underdeveloped countries. HINARI is an initiative by the World Health Organization for providing free or subsidized evidence resources to the economically underprivileged world. The next major issue is the time. In theory, there is ample time to answer a question, or it can go even unanswered. But in clinical practices, there should be an answer, and it is more valuable if it is as early as possible. Finding time for searching and appraisal of information is hardly possible most of the time by the practitioners. The best solution could be establishing a center of evidence-based practices or drug information services to support the practitioners, but then issue of additional cost and resources hits back again. Hopefully some of the newer tools are costly. The additional time required for following evidence-based practices will reduce the number of patient care significantly. Another major barrier is the acceptance of pharmaceutical care plans by other healthcare professionals. Sometimes, if it is not presented in a tactful and digestible way, even the best-quality evidence shall go unimplemented. Also to note that monitoring the outcomes of pharmaceutical care again steals time and resources. It’s a painstaking work to practice evidence-based pharmaceutical care. But maybe that is the only way to go forward (Toklu 2015). In summary, we would like to express that using best-quality evidences is the only way to increase the acceptance of pharmaceutical care in current clinical practice.

332

A. N. Nagappa and S. Bhatt

20.14 Conclusion The beginning of patient-centric care has increased the demand for evidence-based medicine practice. The RCT data is the primary source of data for practice of EBM. Systematic review is helpful in guiding the therapeutic team to quickly assess the situation and quickly take a decision as the information is organized in point-ofquick understanding and application of the same. MA is a process in which all relevant data from RCT is utilized to synthesis of new information. The Network MA is new development which uses live online interactive information in synthesis of data for making decisions in clinical practice and research.

References Akhtar A (2015) The flaws and human harms of animal experimentation. Camb Q Healthc Ethics 24(4):407–419 Al-Jundi A, Sakka S (2017) Critical appraisal of clinical research. J Clin Diagn Res 11(5):1–5 Aslam S, Emmanuel P (2010) Formulating a researchable question: a critical step for facilitating good clinical research. Indian J Sex Transm Dis AIDS 31(1):47–50 Bennadi D (2013) Self-medication: a current challenge. J Basic Clin Pharm 5(1):19–23 Brennan ML, Arlt SP, Belshaw Z et al (2020) Critically appraised topics (CATs) in veterinary medicine: applying evidence in clinical practice. Front Vet Sci 7:314 Houle S (2015) An introduction to the fundamentals of randomized controlled trials in pharmacy research. Can J Hosp Pharm 68(1):28–32. https://doi.org/10.4212/cjhp.v68i1.1422 Kabisch M, Ruckes C, Seibert-Grafe M, Blettner M (2011) Randomized controlled trials: part 17 of a series on evaluation of scientific publications. Dtsch Arztebl Int 108(39):663–668 Masic I, Miokovic M, Muhamedagic B (2008) Evidence based medicine - new approaches and challenges. Acta Inform Med 16(4):219–225 Mathes T, Pieper D (2017) Clarifying the distinction between case series and cohort studies in systematic reviews of comparative studies: potential impact on body of evidence and workload. BMC Med Res Methodol 17(1):107 McDonough RP, Bennett MS (2006) Improving communication skills of pharmacy students through effective precepting. Am J Pharm Educ 70(3):58 Morice AH, McGarvey L, Pavord I (2006) British Thoracic Society cough guideline group. Recommendations for the management of cough in adults. Thorax 61:1–24 Song JW, Chung KC (2010) Observational studies: cohort and case-control studies. Plast Reconstr Surg 126(6):2234–2242 Toklu HZ (2015) Promoting evidence-based practice in pharmacies. Integr Pharm Res Pract 4:127– 131 Uman LS (2011) Systematic reviews and meta-analyses. J Can Acad Child Adolesc Psychiatry 20(1):57–59 World Health Organization (2012) General donor assessment. In: Blood donor selection: guidelines on assessing donor suitability for blood donation. World Health Organization, Geneva