Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine: Volume 1 012817580X, 9780128175804

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Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine

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Integrative Cardiovascular Chinese Medicine Series

Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine Volume 1

Anika Niambi Al-Shura, BSc, MSOM, PhD Niambi Wellness Institute Integrative Cardiovascular Chinese Medicine St. Petersburg, Florida, USA

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright Ó 2020 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-817580-4 For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Stacy Masucci Acquisition Editor: Katie Chan Editorial Project Manager: Tracy Tufaga Production Project Manager: Poulouse Joseph Cover Designer: Matthew Limbert Typeset by TNQ Technologies

In Memory This textbook is dedicated in memory of my late parents. To Mary A Cummings (1954e2006) who passed away of heart failure and other related diseases, I am continuing to keep my promise of finding out what was wrong with you and what could have been done to prevent some of them. To my father AbdurRahman Qurban Al-Shura (1949e80), I followed what you advised me to do in life, and taught me to always find a way to make it happen.

The writing of this textbook is dedicated to my son, Khaleel Shakeer Ryland, and his son, my grandson Khaleem Qurban Ryland. Your ancestors motivated me to find important solutions that may help some people in this world be relieved of suffering. May this legacy inspire and guide you to do the same in this life and to pass our ways on to future descendants.

Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Dr. Al-Shura biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

Chapter 1 Traditional Chinese Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 A brief history of medicine, pharmacology, and formula preparation in traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Constitutional theories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Using traditional Chinese medicines: herbal preparation and delivery types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Most common herbs used in Chinese medicine cardiology. . . . . . . . . . . . 17 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Chapter 2 Nutritional supplements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 History of nutritional supplement regulation in the United States . . . . . 19 Early government regulations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Regulations for future practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 California proposition 65 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Further reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Chapter 3 Pharmaceutical drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Ancient influence on western medicine pharmacology . . . . . . . . . . . . . . . . 26 Recorded Transition toward modern pharmacology . . . . . . . . . . . . . . . . . . . 27 Islamic medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Modern history. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Further reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

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Contents

Section I Anti-hypertensives Chapter 4 Acute, chronic, recovery, and prevention stages . . . . . . . . . . . . . 35 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Section II Anti-arrhythmics Chapter 5 Anti-arrhythmic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

Section III Anti-thrombotic Chapter 6 Acute, chronic, recovery and prevention stages of PVD and DVT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

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Section IV Antibiotics Chapter 7 Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 History and physical examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Clinical workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Treatment approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Section V Anti-atherosclerotics Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

105 109 109 111 113 114 114

Section VI Antiglycemics Chapter 9 Acute, chronic, prevention, and recovery stages . . . . . . . . . . . . 119 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . History and physical examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treatment approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

119 121 123 124 125 125 127

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Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130

Section VII ACE inhibitors Chapter 10 The Chronic stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . History and physical examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treatment approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

135 137 139 139 140 142 142 143 144 145

Section VIII Beta blockers Chapter 11 Acute to chronic stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

151 151 152 152 152 153

Section IX Calcium antagonists Chapter 12 Calcium channel blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

Contents

Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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157 157 159 160 161

Section X Diuretics Chapter 13 Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

165 165 165 166 168 168 169

Section XI Nitrates Chapter 14 Nitrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

173 178 178 179 180 181 183

Section XII Lipid modifiers Chapter 15 Lipid modifiers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188

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Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

188 189 189 191 192

Section XIII Positive inotropes Chapter 16 Inotropic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

195 197 197 198 198 199 200

Section XIV Vasodilators Chapter 17 Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Traditional Chinese medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pharmaceutical drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute and chronic stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recovery and prevention stages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

203 204 204 204 204 204 204

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207

Preface

The Development, Promotion, and Ongoing Research of Integrative Cardiovascular Chinese Medicine Integrative Cardiovascular Chinese Medicine (ICCM) is an area of medical study, research, and education with basic medical sciences, theories, and practices. It was created by Dr. Anika Niambi Al-Shura in 2014 as part of her doctorate degree. Cardiology in Chinese Medicine first became an interest during her early years of study in Chinese hospitals in China in 2004e06. At the time Dr. Al-Shura got a great opportunity to travel to China to work and study. It had dawned on her that before her father died in 1980, he predicted that she would study sciences and travel east to do something important. Dr. Al-Shura decided that she could search for ways to improve on her skills and master’s degree in Oriental Medicine education to help her mother, Mary, suffering from advancing cardiovascular diseases. Before important revelations in medicine and health care became understood in her mission, Mary passed away in her early 50s in 2006. Dr. Al-Shura continued her study and went on to hospital research in China between 2006 and 2014. She was recycling what her father had predicted directly to her word for word, realizing it may have been bigger than finding ways to only help her mother. Realizing that her father’s prediction seemed to be coming true, she used this period to learn and think about how she could have been able to care for Mary and possibly relieved or cured certain cardiovascular disorders had she survived. It became apparent that Mary’s ignored genetic predispositions, lifestyle, and practitioner racial/cultural profiling assumptions about prescribing, maintaining, and prolonging pharmaceutical drug use, and without access to gold star therapies even though the means to afford such therapies were available, were contributors to her advancing condition. Consideration and empathy for these factors from her health-care team and a careful analysis of the condition early on, the method of combining herbal therapy, nutrition, and pharmaceutical drug therapy, had this method been available at the time, may have had a positive impact. Today, Dr. Al-Shura’s work in developing her subject of ICCM is partially in memory of her mother who lived before the dawning of the integrative medicine era. Health-care practitioners, cardiovascular patients, and the public who study from the textbooks in the Integrative Cardiovascular Chinese Medicine series should note the basic medical sciences, theories, and practices which revolve throughout the textbooks, making it necessary to read them first in order then randomly several times. The reader who studies among the integrative cardiovascular Chinese medicine series embarks on a leg of the life

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journey, discovering what small and significant accomplishments one may achieve in their own well-being. Themes which can be found in the textbooks throughout the series are as follows: 1. ICCM acknowledges and integrates the history of the ancient and modern medicine perspectives from cultures around the world. Science and medicine was shared and preserved on some continents while being destroyed or lost on others. 2. ICCM establishes the belief that the human body can be explained through static scientific explanations of anatomy and physiological mechanisms and actions and through dynamic perspectives which brings people together in common and makes each person unique. Personalizing medicine can put analysis and insight into focus and tailor treatment more effectively. 3. ICCM acknowledges that patient autonomy and responsibility is a necessary and primary factor in health and well-being. Patients must enter the health care arena with a clear intention to heal and a detailed narrative that assists in that purpose. They must partner with providers in compliance with what is required to assist health restoration. 4. ICCM establishes the belief in practitioner empathy and the ability to listen, teach, and guide patients. Also, the ability to discern when utilizing one or more than one system of medicine to help a patient who also helps themselves heal. 5. ICCM considers the etiology of diseases as dynamic as the constant changes in modern and urban life. 6. ICCM considers genetic information as crucial as the patient family and personal history. Physical exam and diagnostic methods should involve routine practices of more than one system of medicine. 7. ICCM considers genetic information, innate and seasonal adaptions in body constitution are as crucial as the patient family and personal history. Certain key factors in a patient’s health-care profile make a significant difference when choosing a herbal formula, nutritional supplement, and pharmaceutical drugs singly or in combination in therapy. 8. ICCM establishes the belief that knowledge of herbal constituents in herbs that combine to swiftly restore health are used to make up a single formula or combination of formulations in acute, recovering, and preventive care in cardiology. Knowledge of nutritional deficiencies associated with cardiovascular symptoms helps in dietary planning over a short treatment course or a permanent lifestyle in acute, chronic, recovering, and preventive stages of care. Use of pharmaceutical drugs can assist with acute and chronic conditions where herbs and nutritional intervention is ineffective or the condition has reached a stage of no return to health restoration. Lifestyle modification that helps avoid preventable cardiovascular disorders leads to personal well-being. Chapters in each textbook involve the latest published research from around the world that identifies agreement of theories of principles of ICCM with ongoing research and established protocols of medical science. On of the purposes of exposure of ICCM is to encourage practitioners and patient to adopt our principles when applicable to improve health outcomes and to encourage medical researchers to study our principles and publish

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results in internationally recognized journals. I welcome your constructive comments, suggestions, and ideas which may improve or enhance content for future editions and courses offered for learners. Please write to: Dr. Anika Niambi Al-Shura St. Petersburg, FL, USA

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Dr. Al-Shura biography Dr. Anika Niambi Al-Shura is originally from Louisville, Ky, USA. She has one son, one grandson, and resides in Kentucky and Florida, USA. She enjoys cultivating medicinal plants and formulating medicinal herb recipes, soapmaking, fine art, travelling internationally to meet people for learning new cultures and ways of living, mountain hiking, and relaxing on the beach near the ocean. Dr. Al-Shura has 14 continuous years of formal education involving Traditional Chinese Medicine (TCM) clinical practice, advanced medical study, research and education between the United States, Italy, and China. In 2004, her master’s degree in Oriental Medicine was earned from East West College of Natural Medicine in Florida, USA. In mainland China between 2004 and 2014, she earned hospital study, advanced scholar, and specialty certificates in Chinese medicine, internal medicine, and surgery and cardiology from several university-affiliated hospitals. Those hospitals include Shandong University of Traditional Chinese Medicine, Shandong Provincial Hospital, and Tianjin University of Traditional Chinese Medicine. Her subspecialty training in TCM is in interventional cardiology involving the catherization lab. Dr. Al-Shura earned her PhD in medical education in 2014 through the University Ambrosiana program. Her dissertation on Integrative Cardiovascular Chinese Medicine (ICCM) became her first textbook entitled, Integrative Cardiovascular Chinese Medicine: A Personalized Medicine Perspective. This book was one of 7 textbooks written to introduce the concepts of ICCM. All were published and released together through Elsevier Academic Press in 2014. Those textbooks are utilized for the level 1 program studies in ICCM with continuing medical education (CME) courses. Eight additional textbooks were written on the establishment and development of intermediate ICCM theories and practices. Those textbooks are utilized for the level 2 program CME studies in ICCM. Those 8 textbooks are part of the Integrative Cardiovascular Chinese Medicine series and were published and released together through Elsevier Academic Press in 2019. Dr. Al-Shura is currently a faculty member at Everglades University in Florida, where she teaches medical and healthcare course in the Bachelors of Alternative Medicine program. She also has the Niambi Wellness Institute, based in Florida and Kentucky, where ICCM research and work continues. It includes a natural pharmacy lab and a CME program. The natural pharmacy researches, formulates, manufactures, and distributes various patented and original formulations using TCM herbs. The CME program includes TCM cardiology courses which grant credits towards NCCAOM, state medical board, and state TCM board license renewals in the United States.

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Other Titles by Dr. Anika Niambi Al-Shura • Integrative Cardiovascular Chinese Medicine: A Prevention and Personalized Medicine Perspective • Health Communications in Traditional Chinese Medicine • Integrative Anatomy and Pathophysiology in Traditional Chinese Medicine • Physical Examination in Cardiovascular Chinese Medicine • Diagnosing in cardiovascular Chinese medicine • Essential Treatments in Cardiovascular Chinese Medicine 1: Hyperlipidemia • Advanced Clinical Therapies in Cardiovascular Chinese Medicine

1 Traditional Chinese Medicine Chapter Objectives: 1. Investigate the history of traditional Chinese medicine from antiquity to the modern era. 2. Describe body constitution according to traditional Chinese medicine through body characteristics, pathological characteristics, and recovery suggestions. 3. Describe herbal preparation and delivery types according to traditional Chinese medicine.

A brief history of medicine, pharmacology, and formula preparation in traditional Chinese medicine The history of medicine, identifying pathology of the human body, and treatment methods in Chinese medicine date far into antiquity. The Yellow Emperor was considered by many scholars to be a mythological deity and actual ruler between 2698e2598 BC. Through discussions with advisors, known as ministers, about life and health, the emperor is considered to be the founder of traditional Chinese medicine. Artifacts from the Yin (Shang) Dynasty (1700e1100 BC), which was also during the bronze age, give evidence of folk medicine practices. Taoism, a religious practice of alchemy, involved beliefs of evil supernatural causes and magical treatment of human diseases by shamans. Animal bones, known as oracle bones of Taoists, included scribed records of treatment methods, magical practices, and prescriptions of herbs, food, hot water, and moxibustion. Bronze knives and metal and bone needles were used on and within the body. The Huangdi Nei Jing (Inner Cannon of the Yellow Emperor Classic) may be the oldest medical text still in regular circulation today. The text is estimated to have been compiled by elite scholars who followed the practices of the Yellow Emperor similar to a religion sometime during the Warring States Period (475e221 Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00001-9 Copyright © 2020 Elsevier Inc. All rights reserved.

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BC) of the Western and Eastern Zhou Dynasty (1100e221 BC) and perhaps modified with contemporary influences during the Qin Dynasty (221e207 BC) and Western- Eastern Han Dynasty (206 BCeAD 9 and AD 25e220). Today, the Huangdi Nei Jing is the oldest record in China, which identifies yin and yang, five elements, anatomy and physiology, gender and age directing factors of body constitution and emotions, diet, lifestyle, and environment influencing the development of diseases. The text is based on a compilation of recorded conversations between the Yellow Emperor and his ministers about life and health and is divided into two sections, the Su Wen and the Ling Shu. The Su Wen, known as the Basic Questions, discusses the foundation of diagnosis and the Ling Shu also known as the Miraculous Pivot, discusses acupuncture therapy. Shen Nong lived during the time of Yellow Emperor and developed agricultural practices adopted by local farmers. His knowledge of planting and harvesting food and herbs for medicine was used to treat diseases.

During the Qin and Han dynasties (221 BCeAD 220) Writing, systems of weights and measurements, technology, astronomy, the arts, philosophy, advanced medicine, education, and Confucian laws were developing and the separation of religion (Taoism) and state (Confucianism) brought burning of books considered witchcraft and executions of important scholars. 1. Creation of Shen Nong Ben Cao Jing (Divine Husbandman’s Classic of Materia Medica). This textbook describes 365 herbs and principles of combinations. It is the basis for the development of later additions and creations of other herbal texts. 2. Creation of Shanghan Za Bing Lun (Treatise on Cold-Induced and Miscellaneous Diseases). This textbook is divided into two books: Treatise on Cold-Induced Diseases and Synopsis of the Golden Chamber. It includes prescriptions for general use in clinical practice. 3. Zhang Zhong Jing: Physician who was famous for developing the principles of creating prescriptions, and wrote textbooks for treating infectious and internal medicine diseases. 4. Hua Tuo: One of many famous physicians who studied under Zhang Zhong Jing, famous for the surgical, wu qing xi (five animals) martial arts techniques, acupuncture (hua tuo jia ji points), moxibustion, herbal prescription expertise including use of cannabis in decoctions for anesthesia, and adapting

Chapter 1 Traditional Chinese Medicine

Taoist and Ayurvedic medicine practices in general clinical use. He was executed, and his secrets mostly lost.

Period of middle ages in China Three kingdoms period Western and eastern Jin dynasty Southern dynasty Northern dynasty

AD AD AD AD AD

220e580 220e280 265e420 420e589 386e581

During this period the military was spreading throughout China as well as a heavy influence of Indian culture with the introduction of Buddhism and Ayurvedic medicine. Medical education developed with academies teaching mathematics, astronomy, human sciences, and departments of Chinese medicine. Acupuncture, moxibustion, meridian and pulse, materia medica, and herbal prescriptions books were written and developed by scientists, and famous physicians were practicing and teaching clinical pearls. 1. Creation of Mai Jing (Pulse Classic). This book standardized pulse diagnosis. 2. Zhenjiu Jia Ying (Systemic Classic of Acupuncture and Moxibustion). This book standardized meridian system, acupoints, acupuncture, and moxibustion clinical practices used today. 3. Zhou Hou Jiu Zu Fang (Prescriptions for Emergencies). This book described treatment of diseases in emergency medicine. 4. Ben Cao Jing Ji Zhu (Annotations to the Classic of Materia Medica Significance). This book included farming and harvesting practices of medicinal herbs.

Sui dynasty (AD 581e618) and Tang dynasty (AD 618e907) During this period government-run medical academies opened with two specialties: medicine and pharmacy. The result was the development of a standard pharmacopeia, medical ethics, doctor qualifying examinations, and the importance of holism in medicine. Chinese medicine continued to develop the system of syndrome differentiation and disease classification in internal medicine and surgery, and preserved Taoist, Buddhist and Ayurvedic traditions of grouping acupuncture with massage, cupping, charms, and incantations and to emphasize the importance of spiritualism in medicine.

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1. Creation of Yao Xing Ben Cao (Materia Medica of Medicinal Properties). This book described the four qi as yang ability to penetrate turbidity and awaken digestion and consciousness, and five tastes of herbs that should be used to treat diseases. 2. Tao Hon Jing (AD 452e536) was a famous physician who revised the Shen Nong Ben Cao to classify the herbs according to botanical, mineral and zoological categories, and included additional herbs and described the clinical benefits. 3. Su Jing (AD 657e759) was a famous physician who wrote the Xin Xiu Ben Cao (Newly Revised Materia Medica). The book was illustrated with 844 different herbs and became the pharmacopeia mandated by the government of the Tang Dynasty. 4. Sun Si Miao (AD 581e682) was an imperial physician who mastered medicine, Ayurveda, Buddhism, Confucianism, and Taoism. He was also a famous physician who advocated therapy through diet. He identified treatment for cholera, diarrhea, tuberculosis deficiency disorders, treatment of hypothyroidism with iodine from animal thyroid, treatment of vitamin A deficiencies using animal livers, and B-vitamin deficiencies using herbs. He also developed the a-shi points used today in medical acupuncture and qi gong exercises.

Song dynasty (AD 960e1108) During this period, international silk road and Arab marine trade and exchange involved the export and import of herbs, books, and medical practices. The printing press was invented, resulting in vast publishing and printing of medical books and wide distribution of Chinese medicine texts abroad and medical books about Ayurveda from India. During these periods foreign exchange brought the spread of medical practices between India, Korea, Japan, and Vietnam. Government-run academies dividing medicine and pharmacy developed, resulting in the development of a standard pharmacopeia, medical ethics and doctor qualifying examinations. 1. Tongren Su Xue Zhen Jiu Tu Jing (Illustrated Manual of Bronze Statue Acupuncture). This book provided all meridians and their acupoints. 2. Zhenglei Ben Cao (Classified Materia Medica). This book listed 1558 different prescriptions and illustrations. 3. Xiao Er Yao Zheng Zhi Jue (Key to Differentiation and Treatment of Children’s Diseases). This book was based on pediatrics and congenital (genetic) diseases. 4. You You Xin Shu (New Book of Pediatric Influence). This book described inspection andw examination of children for genetic and acquired illnesses. 5. Cun Zhen Tu (Anatomical Atlas of Truth). This book described anatomy based on performing autopsies.

Chapter 1 Traditional Chinese Medicine

Ming dynasty (AD 1368e644) During this period, agriculture, art, and culture flourished with international exchange and trade in business, including western influences. The Jesuits had arrived and developed a relationship with the Chinese scholars sharing scientific and medical knowledge, philosophy, and religion. Plagues and pestilential epidemics were sweeping the planet. Famous physicians were reinterpreting and revising the ancient Nei Jing and Ben Cao, creating new texts on developments and trends in medicine, and debating important medical philosophies of the day. Texts on gynecology and pediatrics, including congenital conditions, were being written. Three different schools of medicine emerged: School of Nourishing Yin (and quenching the minister fire), School of Warming and Invigoration (by invigorating spleen and stomach to preserve vital energy (qi), the intention of internal medicine), and School of Epidemic Diseases (considered infectious and noninfectious due to exogenous invasion and formerly just as febrile and cold-induced). There were new cases of the outbreak of venereal diseases, especially syphilis, and advancements in surgical techniques involving cancer treatment, methods of analgesia, asepsis, hemostasis, and instruments used in the processes. The development of more advanced and illustrated acupuncture texts and pharmacy and prescription books were promoted and distributed than at any time in history. 1. Pu Ji Fang (Universal Aid Formulary). This book organized prescriptions according to disease and health condition. 2. Nei Ke Zhai Yao (Synopsis of Internal Medicine). This book is considered the first in history dedicated entirely to the study and treatment of internal medicine diseases. 3. Yi Fang Kao (Study on Prescriptions). This book discussed prescriptions according to efficacy, actions of the herbal components, indications and contraindications, and modification suggestions. 4. Zu Sheng Bai Jian (Eight Essays on Life Nourishment). This book discusses disease prevention by nourishing lifestyle and maintaining health.

Qing dynasty (AD 1644e911) During this period the School of Epidemic Diseases developed even further with inoculation studies, especially with small pox to cure the disease, and more advanced textbooks were written. Western medicine began to emerge, bringing U.S. and British political treatises to set up medical offices and hospitals in certain provinces around China. Integrated traditional Chinese medicine emerged, and the abolishment of Chinese medicine was threatened.

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1. Yi Gaun (Key Link of Medicine). This book discussed warming methods of the body and protecting the vital gate or ming men fire. 2. Ben Cao Bei Yao (Essential of Materia Medica). This book discussed health problems associated with smoking tobacco and other drugs. 3. Shi Bing Lun (Treatise on Seasonal Diseases). This book discussed seasonal diseases, causes, pathology, symptoms, diagnosis, and methods of treatment. 4. Zhonxi Hui Tong Yi Shu Wu Zhong (Five Medical Works on Linking up Traditional Chinese with Western Medicine). This book was the first text on integrating the systems of medicine. 5. Xue Zheng Lun (Treatise on Blood Syndromes). This book discusses diseases involving the blood. 6. Hua Yang Zang Xiang Yue Zuan (A Combination of Chinese and Western Illustration). This book provided images of body organs with Chinese and Western discussion of anatomy and physiology. 7. Zhong Xi Hui Tong Yi Jing Jing Yi (Essential Meaning of the Medical Classics from the Perspective of the Convergence of Chinese and Western Medicine). This book discussed the advantages and disadvantages of the exchange of Chinese and western medicine.

Twentieth century China (AD 1912e99) During the first half of the 20th century, previous treaties and trade deals between China and the consulates of United States and Britain concerning the advancement of medicine were being used to modernize China. At this point escalating tensions and World Wars I and II threatened those international relationships, with speculation over whether it was a good or bad thing. Traditional Chinese medicine and western medicine established a coexistence in China, though the rising difficult and complicated political climate threatened the abolishment of Chinese medicine as well. Epidemic plagues and famines led to further abandonment of Chinese medicine for western medicine answers. Professional and medical associations emerged in China and despite government pressure to continue to abolish traditional Chinese medicine, on March 12, 1929 doctors from 132 Chinese medicine associations came together in Shanghai and formed the National Union of Associations for Chinese Medicine. During the second half of the 20th century around the end of World War II, government influences under Mao Ze Dong redirected the anti-Chinese medicine campaign. In efforts to free the nation from dependence on the Soviet Union for medical equipment and pharmaceutical drugs and to become more patriotic and self-reliant, borders were closed to outside western

Chapter 1 Traditional Chinese Medicine

influence. This sparked a nationalistic resurgence of pride in traditional Chinese medicine. In 1954 the Ministry of Health opened the Department of Chinese Medicine and Beijing College of TCM, Shanghai College of TCM, Nanjing College of TCM, Guangzhou College of TCM, and Chengdu College of TCM. During the Great Leap Forward campaign in 1958, around 200 western medicineetrained physicians graduated from a two-year program of traditional Chinese medicine who went on to become administrators during the 1980s and 1990s. It is noted that agricultural hardships led to widespread starvation and diminishing of available herbs leading to 20 million deaths from 1958 to 1962. In 1960, the Great Leap Forward was repealed resulting in private land being returned to peasants. The cultural revolution between 1966e76 was most devastating to the preservation, study, and advancement of medicine in general and traditional Chinese medicine specifically. Medical schools were shut down, medical curriculums and thousands of original and edited textbooks from many dynasties destroyed, students sent to countryside to be reeducated, and physicians and professors killed or imprisoned. The minimally educated barefoot doctor was promoted, and comprised around 1.3 million. The death of Mao Ze Dong in 1976 slowly brought surviving Chinese medicine and western medicine physicians and academics back into society. In 1980 the World Health Organization published around 43 pathologies that can be effectively treated with acupuncture. Between 1980 and 1990 Colleges of Traditional Chinese Medicine and Western Medicine reopened with record enrollment in both. In 1978 The Chinese Society of Cardiology was founded. The Ministry of Health established guidelines for development and coexistence of Chinese Medicine and Western Medicine, publishing houses were established, and in 1987 the Joint Society of World Acupuncture and Moxibustion was founded in Beijing.

Twenty-first century China Acceptance of integration of Chinese and Western medicine is part of everyday healthcare. Clinical trials on herbs with cardiovascular benefits are conducted at universities and pharmaceutical firms across China. Many Chinese medical journals discuss case studies and diagnostic and treatment methods. Students, physicians, and researchers from all over the world study medicine in China. Many medical universities around the world have educational exchange relationships with cardiology departments of traditional Chinese and western medicine universities in China. China Heart Association was established in 2017.

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Constitutional theories

1a 9 Body constitutions in Chinese medicine

Constitution Symptoms

Diet

Neutral

Strong body build, a stable psychoemotional state, energetic adaptable to the environment

Moderate and balanced and free of oily and spicy food

Qi deficient

Easily tired, breathlessness, spontaneous sweating, easily catches the cold or flu, weak immune functioning, tooth marks on tongue sides, sensitive to the environment Cold limbs especially hands and feet, puffy face and pale puffy tongue, diarrhea, throat mucous problems, sensitive to cold and dampness, sensitive to temperature and noise changes in the environment

More qi food and nutrition that invigorates the spleen Avoid garlic, radishes, and cilantro

Thin body build, hot flushes, hot palms and soles, dry mouth, dry stool, irritability, sore throat and fever, preference for cold drinks, sensitive to hot weather environments Skin is painful, dry, course, and easily bruised. Dark circles under eyes, unknown bruises, abnormal growths. Sensitive to windy and cold environments. Overweight body type, profuse sweating, limb heaviness, oily face, a preference for oily and sweet foods, thick tongue coating, sensitivity to rainy and damp environments

More foods that cool such as salads and fresh fruits No foods that heat such as lamb

Yang deficient

Yin deficient

Blood stasis

Phlegm dampness

More food that benefits qi such as red meat Cook food and eat it hot Less raw cold food such as salads and fresh fruits

Lifestyle • Exercises according to age • Optimistic life outlook and positive attitude • Avoid strenuous exercises • Avoid windy areas • Keep warm • Get enough sleep • • • •

Do mild exercise Do saunas Keep warm Avoid living in cold weather towns and prolonged air conditioning • Moderate exercises • Avoid late nights • Avoid wasteful sexual activity that depletes body fluids

More food that promotes blood circulation No fatty meat or dairy products

• Exercises and activities that promotes blood circulation

Eat a bland diet Reduce or avoid sweet food and drinks Include more seaweed in the diet

• Avoid risk factors for diabetes • Avoid risk factors for metabolic syndrome • Avoid risk factors for cardiovascular diseases • Avoid a sedentary lifestyle

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Damp heat

Normal or thin body type, oily skin that is acne prone, bitter taste in the mouth and bad breath, fatigue or body heaviness, heavy urination or unexplained scant urination both with site pain or lower abdominal pain, excessive vaginal discharge, damp scrotum, sensitive to damp and hot environments

Eat less greasy sweet foods Include more seaweed in the diet

Qi stagnation

Thin body build, depressed mood, easily stressed and anxious. Prone to insomnia and diagnosed psycho-emotional disorders, frequent sighing, and chest palpitations. Sensitive to seasonal depression and overcast rainy days

Eat more hawthorn and seaweed

Congenital deficiency

Body is born with weaknesses, allergies and sensitivities to different foods, medicines, smells, pollen and plants. They develop upper respiratory and nasal problems, itchy skin rashes and patches. Extreme sensitivity to outdoor environments and seasonal changes.

Bland diet Avoid spicy food and allergens

• Avoid living in environments that are hot and damp • Incorporate dry and ventilated home environment • Intense exercises recommended • Find relaxing activities to help alleviate emotional irritability • Find relaxing activities to help alleviate emotional irritability • Live in a quiet, clean and bright environment • Engage in organized social activities that bring fulfillment • Intense exercises recommended • Exercises to invigorate immune system • Keep warm when in the cold environments • Living space should be clean and well ventilated

1b Basic seasonal habits for cardiovascular disease prevention Spring

Summer

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Diet: cultivate the yang and regulate the smooth flow of liver qi. Prevent adverse influence on the blood pressure by blending more sour flavors into daily meals. Include sour herbs, which activate yang and immune mechanisms of wei qi, to prepare for the autumn. Exercise: include vigorous activities, jogging, and tai qi, which stretch the muscles and tendons and increase energy; can be done outdoors or indoors due to the weather. Diet: cultivate the yang and regulate the rising of heart yang. Balance bitter, salty, acrid, and sour foods in moderation in daily meals. Eat vegetable soups with various seasonal fruits and vegetables and herbs which maintain body temperature and blood circulation. Drink water and other fluids in moderation to avoid edema.

1bdcontinued Basic seasonal habits for cardiovascular disease prevention

Autumn

Winter

Exercise: moderate activities such as tai qi or sports that stretch the muscles and tendons and maintain energy; can be done outdoors. Diet: nourish the yin and regulate the lung qi and spleen qi. Mix and alternate choices of seasonal vegetables and fruits with sour, bitter, and pungent flavors with sweet and reducing the acrid flavors. Exercise: the accumulated energy of the summer should be stored for the coming winter. Exercise should be moderate to slow. Some activity can be done outside and indoors due to the weather. Diet: nourish the yin and maintain heart and kidney yang balance. Eat less salty and more bitter and acrid food. Exercise: moderate to slow indoor exercises to avoid opening the pores too much and losing yin fluids.

1c Constitution

General body characteristics

Basic male constitutional

Yang type: Excessive amounts of yang and blood, sexual desires, or activities that rapidly deplete essence, yin, and blood. The balance of yin and yang through the nourishment of essence and blood is the life challenge of the male. Yin type: Excessive amounts of qi, insufficient amounts of yang and blood. Pathological evidences are noticed between the menstruation, childbirth and menopausal stages. Balancing yin and yang through building and nourishment of blood is the life challenge of the female. Yang characteristics of rapid development and growth. Potential for excessive heat and fire syndromes in the liver and heart, deficient immunity wei qi, deficient spleen and kidney syndromes. The personality stage is between agreeable and obstinate. Continuous rapid growth and development in adolescence that leads to a plateau in adulthood. Yin and yang are balanced, essence generates, qi moves freely, and blood flows smoothly. Characteristics include the development of mental and emotional individuality, maturity, selfperception, sexuality, morality, virtues, and choices. The personality is changeable. The developmental plateau leads to decline of vitality. Essence is depleted and there is instability of balance between yin, yang, qi, and blood. The personality is stable yet mental and emotional status begins to decline. The viscera, other organs begin to show signs of dysfunction. The menopausal and climacteric stages in both males and females begin. The rapid decline of vitality leads to eventual mortality. Essence has long been depleted with near depletion of immunity wei qi, yin, yang, qi and blood. Stagnation of body fluids accumulates along with poor circulation and elimination. Dampness and phlegm is more abundant. The personality is changeable with mental and physical deterioration.

Basic female constitutional

General stages of infant and childhood constitution

General stages of teenage and young adult constitution

General stages of the middle-aged constitution

General geriatric constitutions

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1d Constitution Basic male constitutional

General prevention suggestions

Diet: foods, drinks, herbs, and supplements that maintain yin and yang balance. Specifics include tonifying yang and building and nourishing blood and kidney essence. Exercise: include activities that move and nourish blood, build and strengthen muscles and tendons, and generate masculine vitality. Basic female constitutional Diet: foods, drinks, herbs and supplements that maintain yin and yang balance. Specifics include nourishing yin and blood before and after monthly discharge, maintaining mood by smoothing and freeing the flow of liver qi, assisting digestion and water metabolism by tonifying spleen qi and kidney qi. Exercise: include activities that move and nourish blood for muscles and tendons, skin and hair, circulation of feminine vitality. General stages of infant and Diet: foods, drinks, herbs and supplements that establish the balance of yin childhood constitution and yang. Specifics include tonifying kidney essence for intelligence, soothing liver qi and reducing heart fire for colic and uncontrollable behavior problems, and tonifying deficiency spleen qi incontinence and drooling. Exercise: activities that promote intelligence, fitness, self-awareness, and responsibility. General stages of teenage and Diet: foods, drinks, herbs, and supplements that maintain the balance of yin young adult constitution and yang. Specifics include tonifying and regulating kidney essence, soothing and smoothing the liver qi, reducing heart fire, tonifying the kidney essence, lung qi, and spleen qi. The focus is to meet the stressors and demands of puberty, emotional stabilization development of selfexpression, irregular dietary habits, career, and physical and sexual activities. Exercise: activities that regulate energy, build and strengthen muscles and tissues, and regulate fat. General stages of the middle-age Diet: foods, drinks, herbs, and supplements that repair the imbalance of yin constitution and yang. Specifics include tonifying and regulating qi, nourishing and moving blood, smoothing the flow liver qi, balancing kidney yin and yang, and promoting activity, relaxation, and sleep. Exercise: activities that promote energy and relieve stress. General geriatric constitutions Diet: foods, drinks, herbs, and supplements that continually work to rebalance yin, yang, qi, blood, and body fluids. Specifics include building and protecting immunity and wei qi, circulation of blood, proper movement of body fluids and wastes, draining dampness, and phlegm accumulation. Exercises: activities that stretch the tendons and muscles and assist with blood and fluid circulation.

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1e Constitution

General pathological characteristics

Yin deficiency constitution

Characteristic: flushed complexion, dry throat, dry skin and hair, emaciated and weak body structure, interior heat sensation at the center of the chest, feverish palms of hands and foot soles, intolerance for summer weather or tropical regions. Behavior: extroverted personality, manic psychoses, hyper sexual desire or activity. Causes: deficiency of yang, innate essence insufficiency, premature delivery, excessive sexual activity, illicit recreational and designer drug use, certain prescription drugs, decline in old age. Characteristic: Pale complexion and lips, obese body structure, muscle atrophy and weakness, cold sensation from the interior and circulating throughout the body. Aversion to cold environments and climates, fluid accumulation especially in limbs and midline, diminished or lack of sexual desire, spontaneous sweating, clear profuse urination and poor or weak defecation, intolerance for winter weather regions. Behavior: introverted personality, depression. Causes: deficiency of yin, premature delivery, insufficient postnatal care; severe emotional trauma, multiple close duration pregnancies/deliveries; weakness and nutritional and emotional imbalance during pregnancy; prolonged illness; perimenopause; certain bacterial, viral, or fungal infections; decline in age. Characteristic: Round chest and/or waistline with cold limbs, edema, shortness of breath and abdominal fullness, fatigue, dull complexion, spontaneous sweating, low voice, no desire to speak much, intolerance for hot summer weather and tropical climates. Behavior: introversion and emotional instability. Causes: deficient innate and acquired essence, anorexia, prolonged or undertreated illness, and advancing age. Characteristic: emaciated appearance, dizziness, muscle atrophy, numbness and tingling of the limbs; pale complexion, eyes, lips, and nails; limp and dull brittle hair and easy hair loss. Behavior: introverted or extroverted personality, depression. Causes: deficient innate essence inheritance; postnatal malnutrition; prolonged untreated illness; severe bacterial, viral, parasitic, or fungal infections; nutritional deficiencies; tumors; irregular menstruation; hemorrhage; illicit and designer drug use; aggressive prescription drug therapies.

Yang deficiency constitution

Yang deficiency constitution

Blood deficiency constitution

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1f Constitution

General pathological characteristics

Qi stagnation

Characteristic: thin body or fluctuating weight gain or a round waistline, intolerance for prolonged heat environments. Behavior: introverted personality, mental instability, emotional sensitivity. Causes: prolonged emotional and psychological trauma due to fright, grief, disappointment, depression, physical and mental overstrain. Characteristic: thin body; abnormally patterned pigmented complexion; dark orbital cavity; purple lips or tongue; hair loss; dry skin calluses or squamation; susceptibility for cold, flu, and infections; intolerance for windy weather and cold climates. Behavior: depressed personality, amnesia, irritability. Causes: inhibited blood circulation, retention of blood in the body, fluid deficiency in the vessels, kidney deficiencies or failure, infections. Characteristic: obese body, protruding soggy waistline, heavy body sensation, oily and sallow skin complexion especially the forehead and nose, acne, puffy face, limb edema, irritable personality, intolerance for damp tropical climates. Causes: heredity, irregular daily routines, unbalanced diet of sweet and fatty food, insufficient water intake, lack of exercise, and irregular sleep schedule. Characteristic: obese body appearance, inability to adapt to a wet tropical environment, oily and dirty or dark yellow complexion and eyes, vexed personality. Causes: exposure to rain, diet of sweet and fatty food, abnormal alcoholic beverage consumption habit, prolonged edema, tropical environments, digestive disturbance, summer heat climate that transforms into the autumn, insufficient fluid circulation, bacterial or viral infection, bladder or kidney infections, liver or kidney failure, gallbladder disorders.

Blood stasis constitution

Damp phlegm constitution

Damp heat constitution

1g Constitution

Recovery suggestions for stagnation, stasis and excess constitutions

Yin deficiency constitution

Diet: foods, drinks, herbs, and supplements that nourish yin and blood and subdue yang hyperenergy. Avoid spicy, hot, astringent, greasy, alcoholic food and beverages. Life: organize and maintain regular daily schedules of waking and sleeping, meals, work, and recreation; avoid overstraining efforts in work, sex; avoid hot weather and rooms, tobacco, marijuana products, OTC remedies, prescription and illicit recreational drugs, which tend to dry yin fluids. Exercise: avoid activities that create a lot of sweating. Diet: foods, drinks, herbs, and supplements that tonify yang and reduce yin by warming the spleen and kidney yang. Avoid cold, raw, bitter, greasy. Life: organize and maintain regular daily schedules of waking and sleeping, meals,

Yang deficiency constitution

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1gdcontinued Constitution

Qi deficiency constitution

Blood deficiency constitution

Recovery suggestions for stagnation, stasis and excess constitutions work, and recreation; avoid cold weather and rooms, tobacco, marijuana products, OTC remedies, prescription and illicit recreational drugs, which tend to deplete the proper accumulation of yang while reducing yin fluids. Exercise: avoid activities in cold or damp environments. Diet: foods, drinks, herbs, and supplements that invigorate the spleen, tonify and nourish the blood, and builds immunity and wei qi. Avoid greasy, cold, bitter, sweet, and spicy Life: organize and maintain regular daily schedules of waking and sleeping, meals, work and recreation avoid tobacco, marijuana products, OTC remedies, prescription, and illicit recreational drugs, which tend to dissipate qi. Exercise: avoid continuous repetitious activity. Diet: foods, drinks, herbs and supplements that tonify and nourish blood flow. Avoid spicy and astringent flavors that vent, dry, or deplete yin fluids. Life: organize and maintain regular daily schedules and limit study times and other periods of concentrated focus. Avoid tobacco, marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to deplete or make the blood dry and apt to stagnation or stasis. Exercise: avoid activities that require a lot brute effort and overstrain.

1h Constitution

Recovery suggestions for stagnation, stasis, and excess constitutions

Qi stagnation

Diet: foods, drinks, herbs, and supplements that promote the regulations of qi of the heart, spleen, lungs, and liver. Avoid cold and astringent products. Life: organize and maintain a regular daily schedule; avoid tobacco and marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to stagnate liver qi. Exercise: avoid activities that require a lot brute effort and mental overstrain. Diet: foods, drinks, herbs, and supplements that invigorate the spleen, promote movement of qi, and move and circulate blood. Avoid spicy and astringent products that vent, dry, or deplete yin fluids, cold and astringent. Life: organize and maintain a regular daily schedule, avoid tobacco, marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to deplete or make the blood dry and apt to stagnation or stasis. Exercise: avoid activities that require a lot of brute effort and overstrain. Diet: foods, drinks, herbs, and supplements that invigorate the spleen qi and yang, drain dampness, and activate the san jiao. This patient is in danger of developing hyperlipidemia and coronary artery disease. Avoid greasy, sweet, cold, and astringent

Blood stasis constitution

Damp phlegm constitution

Chapter 1 Traditional Chinese Medicine

Damp heat constitution

15

flavors, which nourish yin fluids or generate phlegm. Life: organize and maintain regular daily life of sleep, rest, work, and activity. Avoid tobacco, marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to contribute to factors of phlegm stagnation and dampness. Make sure the living environment is dry and free of fungus. Exercise: avoid activities that require a lot brute effort and overstraining, do exercises that allow normal movement sequences such as walking, jogging, taiqi, swimming, etc. Diet: foods, drinks, herbs, and supplements that invigorate the spleen qi, drain dampness, clear heat, and activate the san jiao. This patient may have concurrent kidney, bladder, or vaginal infections. Avoid greasy, sweet, hot, spicy, and astringent flavors, which generate heat. Life: organize and maintain a regular daily schedule, avoid tobacco, marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to be more astringent, compromise the immune system wei qi, and generate heat in the body. Exercise: incorporate activities that require brute effort and vigorous movement to remove the dampness and vent the heat.

Using traditional Chinese medicines: herbal preparation and delivery types There are many herbal preparation methods in Chinese medicine. Tea pills are the most popular because of convenience, followed by granules, powders, tinctures, and finally raw herbal decoctions. Raw herbal decoctions are the least preferred by patients because of direct contact of the herbal brew with the taste buds. If the flavor is unpleasing, it will discourage the patient from continuing medicinal doses during the treatment course. However, the herbal decoction is the most preferred during a treatment course for moderate to severe cardiovascular symptoms. • The suggested hot temperature of the brew has a better chance of assimilating with gastrointestinal processes • The concentration and quick delivery of the herbal constituents dispersed in a decoction can be digested and quickly sent to assist the target meridian and/or organ. • The decoction formula can easily be modified by adding or eliminating herbs for optimal effect. In addition, difficult herbs can be processed separately and either poured into the mouth and chased by the decoction or dissolved into a decoction with the other herbs.

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• Custom decoctions can be made into granules and powders and packaged for portability and convenience of mixing into a cup of hot water. Herbal decoctions for cardiovascular benefit are cooked two to three times to extract all the constituents. • Decoctions that include plant parts such as blossoms and leaves as well as aromatic herbs are processed in small doses. • Decoctions that include the fruit, root, and heavy substances such as bones and shells are processed in large doses. • One or few herb decoctions are processed in large quantities. • Weaker strength decoctions can be taken regularly for prevention and should be given patients in the weaker constitution categories (children, elderly, those with chronic symptoms with debility). • Stronger strength decoctions should be given to patients with acute and chronic conditions in the stronger constitution categories. Doses are subjective as to age, gender, health condition, and severity of disease. They are also indicated and titrated as follows: Prevention: Take once per day around bed time or breakfast. Acute symptoms: Take at any time and in some cases liberally until symptoms abate. Chronic symptoms: Take every 6e8 hours, 2 hours before or after eating a meal. Recovery: Take every 4e6 hours until well-being is restored.

1i Decoction dosage Suggestions According to Constitution Constitution

Prevention/Recovery

Acute

Chronic

Teenage to young adult Age 13e30 Middle age 40e60 Geriatric age 70þ Weak and ill patients

Medium 30e50 g/dose Medium 30e50 g/dose Small 30e50 g/dose

Large 50e100 g/dose Medium 30e50 g/dose Medium 30e50 g/dose

Medium 30e50 g/dose Medium 30e50 g/dose Small 30e50 g/dose

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Most common herbs used in Chinese medicine cardiology

1j Most commonly Used Herbs in Traditional Chinese Medicine Cardiology Herb

Main active constituents

Significance

Kun bu

Iodine, iron, potassium, laminine

Hai zao

Iodine, potassium, mannitol, laminine

Huo xiang

d-limonene, a-patchouline, linalool

Shan zha

Crategolic acid, citric acid, vitamin C

Dang gui

b-sitosterol, vitamin B₁₂,

Shou di huang

b-sitosterol, mannitol, arginine, rehmannin, campesterol Amino acids: arginine, cystadine, glycine, lysine histadine, Nicotinic acid, corynanthine, corynoxeine b-sitosterol, campesterol, baicalin, wogonoside

Lipid, excess fluid and blood pressure reduction Lipid, excess fluid and blood pressure reduction Lipids, digestion, antimicrobial, antiinflammatory Lipids, vasodilation, digestion, antiinflammatory Build blood, blood pressure reduction, reduce LDL Build blood, blood pressure reduction, reduce LDL Build and nourish blood

E jiao Gou teng Huang qin

Gan cao

Mai men dong Hong hua

Chuan xiong Ru xiang

Glycyrrhizin (saponin), coumarins, inositol, folic acid, PABA, arginine, vitamins B₁, B₂, B₃, B₆, flavonoids, b-sitosterol, iron, selenium, zinc, potassium, magnesium b-sitosterol, stigmasterol Carthamin, Omega-6 (linoleic acid) ALA (a-linolenic acid), palmitic acid, oleic acid, arachic acid Ferulic acid, perolyrine, chuanxingol a- and b- boswellic acid, a- and bphellandrine, olibanoresene, pinene

Blood pressure reduction Antimicrobial, immune builder, basal temperature regulation, lipid, excess fluid and blood pressure reduction Lipid reduction, antiinflammatory, antidiabetic, antiallergen, blood pressure reduction Blood pressure reduction, antiinflammatory Lipid reduction, blood pressure reduction, invigorates blood Invigorates blood circulation, reduces blood pressure Invigorates blood circulation, reduces chest pain

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1jdcontinued Most commonly Used Herbs in Traditional Chinese Medicine Cardiology Herb

Main active constituents

Significance

Huang lian Mu dan pi

Berberine, coptisine, ferulic acid, palmatine, jatrorrhizine Paeonol, camperterol

Ban lan gen Dan shen

b-sitosterol, isatin, glutamine, tyrosine, proline Tanishnone, protocatechuic acid

Suan zao ren

Betulinm jujuboside, saponins, betulic acid, ebelin lactone

He shou wu Yu jin Huang qi

Chrysophanic acid, lecithin d- campene, a- and b- curcumene, tumerone D- b-asparagine, b-sitosterol choline, betaine

Du zhong

Alkaloids, potassium, aucubin, glycosides, vitamin C Panaxadiol, ginsenin, panaenic acid, nicotinic acid

Broad-spectrum antimicrobial, antidiabetic, antiinflammatory Reduces edema and blood pressure, antimicrobial, basal temperature regulation Broad-spectrum antimicrobial Invigorates blood circulation, dilates coronary arteries, reduces blood pressure Sedative and analgesic, basal temperature regulation, reduces blood pressure Tonifies the blood, reduces lipids Reduces lipids Reduces blood pressure, reduces blood lipids Reduces blood pressure

Ren shen

Rou cong rong

alkaloids

Reduces or stops arrhythmia, reduces lipids, increases the immune system, reduces stress Blood pressure reduction

References Al-Shura AN. Integrative Cardiovascular Chinese Medicine: A Personalized Medicine Perspective. Elsevier Academic Press; 2014. Dominique H, Marie-Joseph H. A History of Chinese Medicine [Bailey P, Trans]. Edinburgh University Press Ltd.; 1993. State Administration of TCM. Advanced Textbook on Traditional Chinese Medicine and Pharmacology. New World Press; 1995.

2 Nutritional supplements Chapter Objectives: 1. Introduce history and early regulation of nutritional supplementation in the United States. 2. Discuss regulations for future practices. 3. Describe California Proposition 65 as an added protection for consumers of herbal products.

History of nutritional supplement regulation in the United States Plants for food and as herbal remedies have been used since ancient times for health care. In the United States patent medicines using various herbal and nonherbal medicinal substances became popular with widespread advertising to consumers in the 1800s. Without any established regulating government body, discerning between false and genuine remedies was impossible. Competition embarked with private remedy peddlers marketing directly to consumers, while the emerging pharmaceutical industry marketed directly to healthcare providers.

Early government regulations In 1906, the United States government set up the Federal Food and Drugs Act of 1906 and Federal Meat Inspection Act of 1906. The purpose was to address consumer concerns with adulterated products. Regulators established rules, guidelines, inspection schedules, and violations for specific sectors. Those sectors included the processing and hygiene safety practices of the meat and food industries, and manufacturing and product accuracy for patent medicines and drugs. In 1938 the Federal Food, Drug and Cosmetic Act was passed by the United States Congress, which replaced the 1906 Act. Although direct regulation of the meat and food sectors remained, the purpose was for amending and improving the Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00002-0 Copyright © 2020 Elsevier Inc. All rights reserved.

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previous act concerning patent medicines and drugs and to address the emerging vitamin, mineral, botanical ingredient, and cosmetic sectors, which brought in new consumer concerns. The emphasis was to pass the burden of proof upon the herbal remedy and nutritional supplement industries. They needed to declare whether they were marketing products as food or drugs and their intended use. Manufacturers would submit a statement to determine whether their products would be regulated as a food or drug based upon three important language caveats for defining and labeling the finished product: 1. If a finished product was a nutritional supplement or herbal remedy: “. intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals .” 2. If a finished product was an herbal remedy, food, or drug: “. articles (other than food) intended to affect the structure or any function of the body of man or other animals .” 3. If a finished product was a drug: “. recognized in the official U.S. Pharmacopeia (USP), that a product is a drug if it is recognized in the official U.S. Pharmacopeia (USP), official Homeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them.” In 1958, the FDA needed to clarify the status of many newer food substances that came into use after the 1938 act, by considering them as “generally regarded as safe” (GRAS) according to the then established good manufacturing practices (GMP). Vitamins, minerals, and botanicals considered as group and singular-ingredient products were included. The purpose was to establish new statutes for passing additional burden of proof that the manufacturer was neither creating nor marketing finished products that would bring harm to the public, nor should they be regulated as a drug. Manufacturers were required to submit specific documents according to new definitions for food additives. To declare that a product would be GRAS, the language in the definition of a food additive would state: 1. “Any substance the intended use of which results, or may reasonably be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food.” 2. “. if such substance is not generally recognized .” 3. “. to be safe under the conditions of its intended use.” By the 1970s, it became apparent that regulation of vitamins, minerals, and botanical supplements were inconsistent because it was based upon isolated judicial decisions in litigation and loosely enforced federal rules. As a result, in 1973 the FDA

Chapter 2 Nutritional supplements

introduced the U.S. Recommended Daily Allowance (RDA). The purpose was to standardize nutrient content in a finished product. It was declared that a product containing less than 150% of the nutritional guidelines set by the RDA could be considered a food and more than that be considered a drug. The nutritional supplement industry along with consumers protested maximum limits to the U.S. Congress, who in 1976 set up the Proxmire Amendments/Health Research and Services Amendments. The FDA would then be prohibited from using potency of nutritional supplements to establish whether or not to regulate it as a food or drug. The Acts imposing limitations of the potency of a nutritional supplement were later revoked in 1979.

Regulations for future practices By the 1990s federal regulators needed to make distinctions between food additives and nutritional supplements. In 1990, Congress introduced the Nutrition Labeling and Education Act (NLEA) of 1990 to address the increase of unsubstantiated claims of disease cure and erroneous advice despite medical and scientific knowledge of effects of certain substances on the human body. According to regulators, the 1970s and 1980s involved enough cases of serious illness, cardiac arrest, and infant deaths due to the increase of self-help dieting and parenting books. In addition, manufacturers and nutritional products were increasing and expanding to include new substances such as amino acids, which were starting to blur the lines more about what could be considered health-enhancing, like a drug. Consumers and healthcare workers had reported L-tryptophan supplements were connected to eosinophilia-myalgia syndrome, even though other amino acids were increasingly being used by fitness enthusiasts for enhancing workouts and physical body results. Ultimately, under the passage of NLEA in 1993, regulators authorized health claims on nutritional supplement labels despite adverse cases in the public. The authorized health claims allowed for food and nutritional supplements due to a relationship between specific nutrients and certain health conditions if the claims were approved by the FDA under the Dietary Supplement and Health Education Act (DSHEA), which was passed by U.S. Congress into law in 1994. Artificial/alternative sweeteners such as stevia and aspartame became popular as well as various fruit, nut, and other plantbased oils and essences and needed to be defined under DSHEA as well. Under DSHEA, consumers have certain protected rights. Nutritional supplements can be defined as dietary and necessary for wellness promotion. Therefore, they can be considered as food based on the intended use of the supplement.

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The new millennium has considered past experiences of manufacturing practices and consumer demand, justification for keeping a watchful eye on products, and single vitamin, mineral, and botanicals picking up momentum in the market. Though the FDA does not have the authority to impose safety regulations on products or single supplements, or the authority to recall them from consumer use, they do have authority to warn the public when it could have the ability to collect enough publicly known information to do so. Examples include ephedra, pinellia, mutong, comfrey, and foxglove. In 2003, GMPs for the production of dietary supplements for safety from heavy metals, improper raw materials, pesticides, microorganisms, and possibly endangered or protected species were imposed by the FDA under the DSHEA.

California proposition 65 To date there is increased scrutiny on increase of foreign imported substances considered as dietary supplements as well as the introduction of legal hemp and cannabis products into the U.S. market. California has set a precedent as an authority where any supplement sold to consumers in that state would be required to pass certain regulations. Proposition 65, known as the Safe Drinking Water and Toxic Enforcement Act of 1986, concerned herbs considered as a possible carcinogen or reproductive toxicant. It was amended in 2009 to address the legal cannabis industry about marijuana smoke in legal designated establishments as a possible carcinogen, and the use of the pesticides myclobutanil and carbaryl in plant cultivation. New requirements for nutritional supplements imposed in 2016 about heavy metals, goldenseal root powder, nondecolorized whole leaf aloe extract, and naturally occurring constituents pulegone and b-myrocene were set to be enforced in August 2018.

Further reading FDA (Food and Drug Administration). Regulations for the enforcement of the federal food, drug, and cosmetic act. Fed Regist. 1941;6:5921e5926. FDA. Dietary supplements and vitamin and mineral-fortified foods. Fed Regist. 1966;31:15730e15736. FDA. Definitions and standards of identity for food for special dietary use. Dietary supplements of vitamins and minerals. Fed Regist. 1973;38:20730. Wetli CV, Davis JH. Fatal hyperkalemia from accidental overdose of potassium chloride. J Am Med Assoc. 1978;240:1339. FDA. Vitamin and mineral drug products for over-the-counter human use. Fed Regist. 1979;44:16125e16200.

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FDA. The Story of the Laws behind the Labels Part II: 1938dThe Federal Food, Drug, and Cosmetic Act. FDA Consumer. 1981. Barkan ID. Industry invites regulation: the passage of the pure food and drug act of 1906. Am J Public Health. 1985;75:18e26. Young AL, Bass IS. The dietary supplement health and education act. Food Drug Law J. 1995;50:285e292. FDA. FDA Backgrounder. Milestones in U.S. Food and Drug Law History. 2002. Online. Hartz SC, Otradovec CL, McGandy RB, et al. Nutrient supplement use by healthy elderly. J Am Coll Nutr. 1988;7:119e128. NBJ’s Annual Industry Overview VIII. Nutr Bus J. 2003;8:1e9. Nesheim MC. What is the research base for the use of dietary supplements? 1999. Publ Health Nutr 2:35e38 State of California Health and Safety Code section 25249.5 et seq. The Safe Drinking Water and Toxic Enforcement Act of 1986, Commonly Known as “Proposition 65”. Hereafter Referred to as “Proposition 65” or “The Act”. State of California Article 6 of Title 27. California Code of Regulations, Section 25600 et seq amendment August 2016.

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3 Pharmaceutical drugs Chapter Objectives: 1. Introduce the integrative cardiovascular Chinese medicine perspective on pharmacology. 2. Introduce some recorded ancient influences on general pharmacology. 3. Introduce ancient scientists and physicians of many cultures internationally who contributed to medicine in general and pharmacology specifically. 4. Introduce the scientists and physicians in modern history who have contributed to medicine in general and pharmacology specifically. 5. Introduce some terminology in pharmacology.

Pharmacology is the study of the interactions that occur between a living organism and any natural, synthetic, or endogenous substance on the organism that exerts a biochemical or physiological effect on the cell, tissue, organ, or organ system, and with a normal or abnormal effect. This involves: 1. Drug composition and properties 2. Synthesis and drug design 3. Molecular and cellular mechanisms 4. Organ/system mechanisms 5. Signal transduction/cellular communication 6. Molecular diagnostics 7. Interactions 8. Toxicology 9. Chemical biology therapy, medical applications, and antipathogenic capabilities Modern pharmacology as a biomedical science was developed during the 19th century. It has evolved by continuous study of biological mechanisms, biochemistry, and genetics to adapt medicines into more effective tools against pathogenic factors and disease. The purpose is to provide tools for prevention, treatment, and personalized medicine. Pharmacology involves two distinct areas of study: Pharmacodynamics: the effects of chemicals on a biological system of receptors. Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00003-2 Copyright © 2020 Elsevier Inc. All rights reserved.

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Pharmacokinetics: the effect of the biological system dynamics of absorption, distribution, metabolism, and excretion of biological systems on a drug. The creation of stable drugs for use involves the cooperation between scientists of various disciplines and purposes. First, the medicinal chemist creates a medicinal compound. Next, pharmacologists test existing substances for medicinal stability and develop new medicines. The criteria for determining substances for medicinal use involve: • Screening for desired activity of the constituents • Determining mode of action for indications • Quantifying drug activity for the indicated use The pharmacologist approves the compound for successful physiological activity and therapeutic effect. Next, toxicologists and microbiologists test for indication and dosage. Healthcare clinicians provide the cohorts for collecting evidence and experience of therapeutic effects.

Ancient influence on western medicine pharmacology During the times of antiquity, healers from various indigenous cultures around the world were collectively called, “witch doctors”. Many were skilled in the use of local herbal substances to holistically treat the mind, body, and soul of people in their community. They were focused more on natural substances including plant, mineral, animal, and human sources. They were considered practitioners of magical arts associated with their cultural belief systems. Usually little or no recorded information can be found to depict and understand the knowledge and practice of such people. However, in ancient Egypt, pharmacological knowledge was recorded on papyrus. Two examples are Ebers Papyrus from 1550 BC, and the Edwin Smith Papyrus from the 16th century BC. Ancient mummies in Egypt and parts of Sudan included a kind of beer infused with tetracycline, an antibiotic. These early healers were known by many names in parts of the world where their practices influenced transitions toward modern day pharmacology. • African Continent: Babalawo, Adahunse, Oniseegun, Abia ibok, Dibia, Boka, Sangoma, Nganga • Asian Continent: Wu Yi, Zhubo, Kashaf, Pharmakeia, Sihr, jhakri, Dayan, Kitsune, Hanja, Curandero, Bomoh, juju, isangoma • European Continent: Sorcerer, Wizard, Pellers, Hexenmeister, Maghiardzha, De Kloka

Chapter 3 Pharmaceutical drugs

Recorded Transition toward modern pharmacology Hippocrates (460e377 BC) • • • • • •

•

Considered the founder of western medicine Transformed medicine from superstition and magic into a healthcare system based on a scientific uniform of clinical protocol Created the Hippocratic Corpus, which includes his lectures, medical notes, books, essays, and research Taught physicians to be calm, honest, understanding, smart, and serious Taught physicians to keep separate detailed record of observations and clinical diagnosis and treatment methods for each patient Developed a homeopathetic theory that a human body has the power to heal itself based on the four humors: blood, black bile, yellow bile, and phlegm Observed that the disease can be classified as family inheritance, natural environment, lifestyle, and food habits; acute, chronic, endemic, and epidemic; and would either subside or increase, leading eventually to the death of the patient

Islamic medicine During the middle ages, pharmacology advanced further because of innovations in botanical sciences and chemistry. • The first state-regulated pharmacies were established in Baghdad in AD 754 under the Abbasid Caliphate. zi Rhazes (AD 865e915) promoted • Muhammad ibn Zakarıya Ra the use of chemical compounds in medicines. • Abu al-Qasim al-Zahrawi Abulcasis (AD 936e1013) wrote the Liber Servitoris, which described how to make simple medicinal recipes from which complex drugs could be created. • Sabur Ibn Sahl (died AD 869) initiated the order of a pharmacopedia with detailed instructions about drugs for various diseases. • Al-Biruni (AD 973e1050) wrote the Kitab al-Saydalah (The Book of Drugs). He discussed the role of the pharmacist, properties of various medicines, and how to use them. • Ibn Sina (Avicenna) wrote The Canon of Medicine, which described 700 medicines with recipes, actions, and indications. • Al-Maridini of Baghdad and Cairo and Ibn al-Wafid (AD 1008e1074) wrote texts on uses of medicines, which later were printed in Latin as De Medicinis Universalibus et Particularibus, by Mesue and as the Medicamentis simplicibus by Abenguefit.

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• Peter of Abano (AD 1250e1316) translated and added a supplemental section of information in the text De Veneris, which was written by Al-Maridini. • Al-Muwaffaq (AD 842e910) wrote The Foundations of the True Properties of Remedies. The text described distinction and uses of sodium carbonate and potassium carbonate and poisonous elements such as arsenic, copper, and distillation of seawater for drinking.

Modern history Originating in the 19th and 20th centuries, pharmacology developed many techniques and study designs for creating and testing new drugs. • François Magendie: In 1809 he presented his work to the Paris Academy. It involved the convulsant action of strychnine, a constituent of nux vomica, on the spinal cord of dogs. • Friedrich Wohler: By 1828, he had challenged the vital force theory by synthesizing urea from inorganic substances. This led to developing organic chemistry. • Oswald Schmiedeberg (1838e921): He is recognized as the founder of modern pharmacology. • Claude Bernard: In 1842, he discovered that alkaloid constituents in curare plants interrupt the stimulation of muscle by nerve impulses at the neuromuscular junction. • Jean-François Heymans: In 1842, he worked with a harvested heart from a mammal while Claude Bernard experimented with stimulation of nerve impulses. • Karl Ludwig: In 1840 he invented a kymograph, which records motion or pressure, which was used as a crude device to monitor blood pressure. • Arnold Berthold: In 1849, he transplanted testicular tissue into a rooster to prove it would induce growth of the comb. His method initiated the study of male sex hormones. • Edgar Allen and Edward Doisy: In 1924, they used rats in three studies. The first was to remove the ovaries from rats to study estrogen. The second was to inject them with Freund’s adjuvant, which is a serum of dead bacteria, to study antiinflammatory agents. The third was to test the effects of gastric secretion by forming a vagally denervated Heidenhain pouch, which has an opening through the abdominal wall. Oswald Schmiedeberg (1838e921) • •

He obtained his medical doctorate in 1866 with a thesis on the measurement of chloroform in blood. He became professor of pharmacology at the University of Strasburg and studied chloroform and chloralhydrate.

Chapter 3 Pharmaceutical drugs

•

• • •

During his 46-year tenure at University of Strasburg, he trained most of the scientists who became professors at other German universities and around the world. He was responsible for the development of the German pharmaceutical industry up to World War II. In 1869 he showed that muscarine had the same effect on the heart as electrical stimulation of the vagus nerve. In 1878, he published Outline of Pharmacology. In 1885, he introduced urethane as a hypnotic.

John Jacob Abel (1857e938) • • • •

•

An American biochemist and pharmacologist Studied under Oswald Schmiedeberg In 1890, he became the first chair in pharmacology at the University of Michigan. In 1893, he began research at Johns Hopkins University: • 1898: isolation of epinephrine from adrenal gland extracts • 1919: isolation of histamine from pituitary extract • 1926: preparation of pure crystalline insulin His student, Reid Hunt, discovered acetylcholine in adrenal extracts in 1906.

The development of drugs for categories of heart and vascular diseases requires study and design of constituents to act on cell receptors and signaling pathways. Drugs have a narrow or wide therapeutic index or therapeutic window, which is the ratio between the desired effect to toxic effect.

Therapeutic index Narrow index: The desired effect occurs at or close to a toxic dose. The drug is difficult to administer to the patient because it requires close monitoring; for example, antibiotics, warfarin, aminoglycosides, and so on. Wide index: The desired effect occurs below the toxic dose. The drug is easier to administer to the patient because it requires less or no direct monitoring.

Active pharmaceutical ingredient The pharmacokinetics of the drug is also known as the active pharmaceutical ingredient (API). When studying the API, scientists are interested in the LADME: • Liberation: How the API is released from the medication (dissolving, etc.) • Absorption: How the API is absorbed (mouth, skin or intestine)

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• Distribution: How the API is spread through the organism • Metabolism: How the API is converted into active, toxic, or inactive ingredients once inside the body • Excretion: How the API is eliminated from the body, through either breath, skin, urine, bowels, and so on. Screening of candidate compounds and mode-of-action studies may focus on specific tissues, organs, or systems or on actions, such as antihistaminic or anticonvulsant. As knowledge of human biochemistry and molecular biology advances, pharmacology zeroes in more often on enzymatic action and receptors. Clinical pharmacology: focuses on principles and methods in the medical clinic and toward patient care and outcomes. Cardiovascular pharmacology: focuses on the effects of drugs throughout the cardiovascular system. Pharmacogenetics: focuses on the different responses to drugs based on genetic variation. Pharmacogenomics: focuses on the genomics technologies to personalize new drugs and old classifications. Posology: focuses on drug dosage based on age, sex, weight, genetics, elimination rate, and time of administration.

Further reading Titsingh I. Annales des Empereurs du Japon. 1834:434. Levey M. Early Arabic Pharmacology. Leiden: E. J. Brill; 1973. Kremers E, Sonnedecker G. Kremers and Urdang’s History of Pharmacy. Amer. Inst. History of Pharmacy; 1986:17. ISBN 0-931292-17-4. Oldham FK, Kelsey FE, Geiling EMK. Essentials of Pharmacology. Philadelphia: Lippincott; 1955. Sneader W. Drug Discovery: The Evolution of Modern Medicines. New York: Wiley; 1985. Oldham FK, Kelsey FE, Geiling EMK. Essentials of Pharmacology. Philadelphia: Lippincott; 1955. Sneader W. Drug Discovery: The Evolution of Modern Medicines. New York: Wiley; 1985. Holmstedt B, Liljestrand G. Readings in Pharmacology. New York: MacMillan; 1963. Leake CD. An Historical Account of Pharmacology to the Twentieth Century. Springfield, IL: Charles C. Thomas; 1975. Holmstedt B, Liljestrand G. Readings in Pharmacology. New York: MacMillan; 1963. Hadzovic S. Pharmacy and the great contribution of Arab-Islamic science to its development. Med Arh. 1997;51(1e2). ISSN: 0025-8083:47e50. OCLC 32564530. Ellis L. Archaeological Method and Theory: An Encyclopedia. Taylor & Francis; 2000:443e448. ISBN 978-0-8153-1305-2.

Chapter 3 Pharmaceutical drugs

Borchardt JK. The beginnings of drug therapy: ancient mesopotamian medicine. Drug News Perspect. 2002;15(3). ISSN: 0214-0934:187e192. https://doi.org/ 10.1358/dnp.2002.15.3.840015. PMID 12677263. Al-Ghazal SK. The valuable contributions of Al-Razi (Rhazes) in the history of pharmacy during the middle ages. J Int Soc Hist Islam Med. October 2003; 2(4). ISSN: 1303-667X:9e11. OCLC 54045642. Abdullahi AJ. Trends and challenges of traditional medicine in Africa. Tradit Complement Altern Med. 2011;8(S):115e123.

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Anti-hypertensives

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4 Acute, chronic, recovery, and prevention stages Chapter Objectives 1. Introduce atherosclerosis as a disease seen in integrative cardiovascular Chinese medicine. 2. Understand the definition and classification of hypertension. 3. Understand the etiology and pathophysiology of hypertension. 4. Introduce the history and physical examination procedures for monitoring hypertension. 5. Understand what involves a hypertensive emergency. 6. Introduce the methods of differential diagnoses. Introduce steps in the clinical workup. 7. Introduce treatment approaches according to Western medicine. 8. Introduce traditional Chinese medicine formulas for hypertension. 9. Introduce nutritional supplements for atherosclerosis. 10. Introduce pharmaceutical drugs for hypertension. 11. Discuss a perspective for treating patients with traditional Chinese herbal medicine, nutritional supplements, and/or pharmaceutical drugs in the acute and chronic stages. 12. Discuss a perspective for treating patients with traditional Chinese herbal medicine, nutritional supplements, and/or pharmaceutical drugs in the recovery and prevention stages.

Background Hypertension is a risk factor for congestive heart failure, coronary artery disease, peripheral vascular disease, renal failure, and stroke.

Definition and classification Defining and determining what an abnormally high blood pressure means to overall health is very difficult. The JNC 7 (see Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00004-4 Copyright © 2020 Elsevier Inc. All rights reserved.

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Table 4.1 JNC 7 classification of Blood Pressure for adults age 18D Normal Prehypertension Stage 1 Stage 2

Systolic Systolic Systolic Systolic

lower than 120 mm Hg 120e139 mm Hg 140e159 mm Hg 160 mm Hg or greater

Diastolic Diastolic Diastolic Diastolic

lower than 80 mm Hg 80e89 mm Hg 90e99 mm Hg 100 mm Hg or greater

Table 4.2 End organ system dysfunction due to hypertension Neurologic Cardiovascular Other

Encephalopathy, cerebral vascular accident subarachnoid and hemorrhage Acute left ventricular dysfunction, acute pulmonary edema, aortic dissection, unstable angina pectoris, and myocardial infarction Acute renal failure/insufficiency, retinopathy, hemolytic anemia

Table 4.1) and JNC 8 classification systems help make decisions about treatment directions. The purpose of determining hypertension is not necessarily to treat the symptom, but to understand how untreated or undertreated hypertension can lead to what end-stage disorder. (see Table 4.2).

Pathophysiology The progression of essential hypertension is as follows: • Prehypertension: ages 10e30, through increased cardiac output • Early hypertension: ages 20e40 years through increased peripheral resistance • Establishment of hypertension: ages 30e50 • Complicated hypertension: ages 40e60 Factors possibly involved in essential hypertension: • Genetic predisposition

Chapter 4 Acute, chronic, recovery, and prevention stages

• • • •

Diet (excess salt intake) Adrenergic tone Renal infiltration Pathologic immunosuppression T lymphocytes and T-cell derived cytokines (interleukin 17 and tumor necrosis factor alpha) • Cortisol reactivity, which is a hypothalamic pituitary function

Etiology The genetic contributors Genome-wide association studies have revealed multiple gene loci in known pathways of hypertension as well as DNA methylation in the developing fetal kidney nephrons and histone modification. Poor water and protein intake predict preeclampsia, and emotional stress causes a DNA methylase trigger of autonomic responses in pregnancy and increases expression of reninangiotensin in the developing fetus.

Causes of secondary hypertension • Obstructive sleep apnea • Renovascular hypertension • Oral contraceptive use triggers estrogen activating hepatic synthesis of angiotensinogen, which actives the renninangiotensin-aldosterone system • Nonsteroidal antiinflammatory drugs inhibit the vasodilating effects of prostaglandins and the production of vasoconstricting factors in a controlled hypertensive patient. • Primary hyperaldosteronism as marked hypertension: renal sodium retention, kaliuresis, hypokalemia, and hypochloremic metabolic alkalosis. Increase in intravascular volume leads to an increase in blood pressure.

History Findings in the medical history: • History of known renal disease • Abdominal masses • Anemia • Sweating • Palpitations • Cold or heat tolerance • Lack of energy • Bradycardia or tachycardia

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• • • • • • • • •

Hypothyroidism or hyperthyroidism Sleep apnea may be noted Weakness suggests hyperaldosteronism Kidney stones suggest hyperparathyroidism Lifestyle factors: Family history Metabolic syndrome, including elevated cholesterol levels and diabetes Tobacco use Age 45 and over Lack of exercise

Physical examination • The physical examination should determine the stage of hypertension and presence of end-organ dysfunction (see Table 4.2). • Let the patient rest quietly for 5 minutes. Assess volume depletion by measuring blood pressure in both the supine and the standing positions. Assess coarctation of aorta or subclavian artery stenosis by measuring blood pressure in both arms and one leg. • Calculate an average of three blood pressure readings taken 2 minutes apart. • Evaluate signs of left ventricular hypertrophy (LVH) including enlarged apical impulse, and the presence of an S4. • Palpate peripheral pulses (see Table 4.3). • Check the eyes for hypertensive retinopathy. • Confirmed after an elevated blood pressure (see Table 4.1).

Hypertensive emergencies A high blood pressure reading is potentially dangerous and may necessitate calling first responder emergency services to rescue a patient and transport to a hospital. A high systolic pressure of

Table 4.3 Hypertension Femoral Bruit

Absent, weak, or delayed femoral pulses suggest coarctation of the aorta or severe peripheral vascular disease Check neck for carotid bruits, distended veins, or enlarged thyroid gland. Listen for renal artery bruit over the upper abdomen; the presence of a bruit with both a systolic and diastolic component suggests renal artery stenosis.

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more than 160 mm Hg and a diastolic pressure of more than 100 mm Hg or a systolic pressure of more than 160 mm Hg are potentially associated with: • Increase in heart mass caused principally by LVH is connected with arrhythmia leading to death • Cerebrovascular edema and microhemorrhage: hypertensive hemorrhage, hypertensive encephalopathy, and dementia due to dysfunction of cerebral autoregulation Common clinical presentations of hypertensive emergencies: • Cerebral infarction • Pulmonary edema • Hypertensive encephalopathy • Congestive heart failure • Intracranial hemorrhage • Aortic dissection • Eclampsia • Acute myocardial infarction • Hypertension is also one of several conditions that have been increasingly recognized as having an association with • Posterior reversible encephalopathy syndrome: headache, seizures, altered visual and mental disturbances

Differential diagnosis Patients with a history of marked blood pressure elevations over a certain period should determine future health through ambulatory blood pressure monitoring and hypertension screening tests (see Table 4.4).

Table 4.4 Hypertension screening tests Condition

Screening test

Sleep apnea Thyroid and parathyroid Renovascular hypertension Pheochromocytoma Mineralocorticoid excess (adrenals) Drug related (illicit or prescribed)

Sleep study with oxygen saturation and epworth sleepiness scale TSH and serum parathyroid hormone Doppler ultrasonography, MRI, and CT 24 hour urinary metanephrine and normetanephrine 24 hour plasma aldosterone-to-renin activity ratio and mineralocorticoid Drug screen

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Ambulatory blood pressure monitoring Patients with a history of blood pressure elevations over a certain period of time should monitor at different times of the 24 hour day at home. Ambulatory blood pressure monitoring (ABPM) is used to monitor daily and nocturnal blood pressure. In general, these readings are lower than those in a physician office, which causes white-coat hypertension, however hypertensive patients with a 24 hour blood pressure greater than 135/85 mm Hg have been shown to have almost double the likelihood of a future cardiovascular event. Benefits of ABPM include: • A better understanding of blood pressure correlation with target-organ injury • Information that can be calculated into percentages of personal incidence for study such as number of elevated blood pressure readings, overall blood pressure load, and extent of blood pressure fall or elevation during sleep.

Clinical workup Baseline laboratory evaluation Initial workup • Urinalysis • Complete blood count (CBC) • Fasting blood glucose or A1c • Hematocrit • Serum sodium • Potassium • Creatinine: glomerular filtration rate (GFR). An increase in cardiovascular risk is associated with a decreased GFR level and with albuminuria and blood flow through kidneys. • Calcium • Lipid profile following a 9e12 hour fast (total cholesterol, highdensity lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) Assessment of suspected secondary causes and evidence of targetorgan disease • CBC • Chest radiograph • Uric acid and urine microalbumin

Chapter 4 Acute, chronic, recovery, and prevention stages

Screening tests See Table 4.4. Tests that evaluate results of hypertensive emergencies: • Electrolytes • Blood urea nitrogen • Creatinine levels are used to identify renal impairment. • CBC and smear help exclude microangiopathic anemia. • Renal impairment: dipstick urinalysis can be used to detect hematuria or proteinuria; microscopic urinalysis can be used to detect RBCs or RBC casts. • Toxicology screen • Pregnancy test • Endocrine tests Radiologic studies These are generally ordered when there is suspicion of advanced renal damage, specifically renal artery stenosis: • Noninvasive: computed tomographic angiography, magnetic resonance angiography • Invasive: renal angiography Echocardiography Evaluates for end-organ damage in a patient with borderline high blood pressure: • LVH despite normal or borderline-high BP measurements requires antihypertensive therapy. • Detects left atrial dilatation and left ventricular dysfunction (diastolic or systolic) more frequently than electrocardiography • Prognosis for hypertension with coronary artery disease (CAD)

Treatment approaches Lifestyle modifications If at least one antihypertensive medication or herbal formula when indicated is taken at bedtime, it can produce a reduction of 5 mm Hg in the nocturnal mean blood pressure and 20% reduction of future cardiovascular events.

Cholesterol level targets The American Association of Clinical Endocrinologists/American College of Endocrinology now recommends: Extreme-risk patients: Goals: LDL < 55 mg/dL, nonHDL < 80 mg/dL, apolipoprotein B (apoB) < 70 mg/dL

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• Progressive atherosclerotic cardiovascular disease (ASCVD), including unstable angina, in patients after achieving an LDL-C < 70 mg/dL • Established clinical cardiovascular disease in patients with diabetes, chronic kidney disease (CKD) stages 3/4, or heterozygous familial hypercholesterolemia (HeFH) • History of premature ASCVD (20% • Diabetes or CKD stages 3/4 with one or more risk factors • HeFH High-risk patients: Goals: LDL < 100 mg/dL, nonHDL < 130 mg/dL, apoB < 90 mg/dL • Two or more risk factors and 10 years risk 10%e20% • Diabetes or CKD stages 3/4 with no other risk factors Moderate-risk patients: Goals: Same goals as high-risk • Two or more risk factors and 10 y risk < 10% Low-risk patients: Goals: LDL < 130 mg/dL, nonHDL < 160 mg/dL, apoB not relevant • 0 risk factors

Surgical intervention • Aortorenal bypass using a saphenous vein graft or a hypogastric artery • Renal artery angioplasty with stenting • Pheochromocytoma: surgical resection with a unilateral solitary aldosterone-producing adenoma, resolving hypertension by tumor resection • Angioplasty • Renal artery denervation

Dietary changes • Daily consumption of sodium chloride not exceeding 6 g • DASH eating plan encompasses a diet rich in fruits, vegetables, and low-fat dairy products with additional monitoring of protein intake for patients with diabetes. • Daily intake of potassium, calcium, and magnesium

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Weight loss and exercise Most patients with hypertension are more than 20% overweight and associated with insulin resistance and hypertension. • Improved insulin sensitivity and blood pressure can occur with every 5% reduction in weight. • Lowering blood pressure by 5e20 mm Hg can occur with every 6 lb reduction of weight.

Pharmacologic therapy JNC 8 guidelines no longer recommend only thiazide-type diuretics as the initial therapy in most patients, instead suggesting certain drugs specific to racial profiling (see Tables 4.5 and 4.6)

Table 4.5 Suggested Hypertension Treatment Based on U.S. Racial Profiles Black Patients Non-black patients

Calcium channel blockers (CCBs) and thiazide diuretics ACEI/ARB CCBs and thiazide diuretics

Table 4.6 Traditional Chinese Medicine Formulas for Hypertension Herbal medicine

Action

Modified gambirplant branch formula Modified yang hyperactivity check with 7-drug formula Modified liver subduing and wind stopping formula Modified blood pressure reducing decoction Modified qi replenishing and yin nourishing formula Modified cardiotonic formula

Reduces hypertension symptoms, headache, and dizziness Reduces hypertension symptoms, headache, and tinnitus; mildly diuretic Reduces hypertension, thyroid problems, hyperaldosteronism, and tranquilizes the mind Reduces blood pressure, dreaminess, insomnia, brain fog, and chest oppression Stabilizes blood pressure while recovering from dryness, exhaustion, and headache Reduces blood pressure, nourishes blood

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Heart failure: Diuretic, beta-blocker, Angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), aldosterone antagonist. Following myocardial infarction: beta-blocker, ACEI Diabetes: ACEI/ARB Chronic kidney disease: ACEI/ARB

Management of diabetes and hypertension Diabetes risk is three times higher in patients with hypertension within 5 years. Hypertension risk is high in diabetic patients. Blood pressure must be maintained at or below 130/80. Hypertension and diabetes are risk factors for: • Cardiovascular disease • Stroke • End-stage renal disease • Diabetic retinopathy

Traditional Chinese medicine Nutritional supplements Alpha lipoic acid Nutritional constituents: Lipoic acid Benefits: Targets nerve cells, kidney, and liver; lowers blood pressure, prevents cell damage to improve insulin use Caution: May lower blood sugar too much; avoid in pregnancy and nursing

Cod liver oil Nutritional constituents: Vitamins A, D, and omega-3 fatty acids (fish oils, flax seed, primrose, borage, and flaxseed oils) Benefits: Reduces cardiometabolic risk factors, protects sudden cardiac death after myocardial infarction, reduces raised plasma triglycerides, reduces blood pressure, and ameliorates atherogenic effects Caution: High doses required for reduction of blood pressure may have side effects.

Chapter 4 Acute, chronic, recovery, and prevention stages

Coenzyme Q-10 Nutritional constituents: CoQ10 Benefits: Heart, muscle, liver, and lungs; improves glycemic index, myocardial energy Caution: Body stores reduced when glyburide is prescribed for diabetes

Chromium Nutritional constituents: Picolinate, chloride, and nicotinate Benefits: Pancreatic functioning and blood sugar Caution: May lower blood sugar excessively, causing concerns with medication indications

Magnesium Nutritional constituents: Citrate, stearate, and sulfate forms Benefits: Heart, kidneys, and muscle; improves type 2 insulin utilization in elderly Caution: May induce excessive stool elimination and diarrhea in patients at risk of inflammatory bowel disorders

Potassium Nutritional constituents: Citrate Benefits: Cell membranes, reduces blood pressure Caution: May cause sodium retention and increased blood pressure

Chromium Nutritional constituents: Picolinate, chloride, and nicotinate Benefits: Pancreatic functioning and blood sugar Caution: May lower blood sugar excessively, causing concerns with medication indications

Selenium Nutritional constituents: Chelate Benefits: Small intestine and kidneys; helps protect nerves and vessels from excessive sugar intake damage Caution: Low levels may predispose to cancer, diabetes, and CAD.

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Vitamin B6 and Folic acid Nutritional constituents: Pyridoxine and folate Benefits: Liver, jejunum, ileum, and kidney; combined with B12 helps prevent stroke and loss of limbs and vision due to diabetes Caution: Excessive use of B6 may cause disfiguring skin lesions or folic acid nerve damage.

Vanadium Nutritional constituents: Sulfates and chelates Benefits: Liver and muscle cells to utilize insulin Caution: Nausea and cramping leading to diarrhea

Zinc Nutritional constituents: Picolinate Benefits: Production, storage, and secretion of insulin; blood sugar diffuses into cells Caution: May cause headache, nausea, vomiting, and drowsiness

Pharmaceutical drugs Adrenergic agent This drug is for mild hypertension and is often used with other antihypertensive drugs for more severe hypertension.

Aldosterone antagonists These selective drugs compete with aldosterone receptor sites, reducing blood pressure and sodium reabsorption.

Alpha-blockers These drugs selectively block postsynaptic alpha1-adrenergic receptors and lower blood pressure by dilating arterioles and veins. Side effects include dizziness, headache, and drowsiness, in addition to orthostatic and first-dose hypotension.

Angiotensin converting enzyme inhibitors See Chapter10.

Chapter 4 Acute, chronic, recovery, and prevention stages

Angiotensin receptor blockers See Chapter 10.

Beta-blockers See Chapter 11.

Calcium channel blockers See Chapter 12.

Central-acting alpha 2-agonists These drugs stimulate presynaptic alpha 2-adrenergic receptors in the brain stem, which reduces sympathetic nervous activity.

Diuretics Loop diuretics These drugs are commonly used to control the retention of urine volume and are more commonly prescribed for decreased GFR or heart failure. They act on the ascending limb of the loop of Henle, inhibiting the reabsorption of sodium and chloride. They are protein-bound, entering the urine by tubular secretion in the proximal tubule. They are frequently used alone, but better with other medications.

Potassium sparing These drugs decrease potassium secretion, interfere with sodium reabsorption in the collecting duct region of the nephron (distant tubules), and when used alone, have a weak diuretic and antihypertensive effect.

Thiazides These drugs can be used alone or with other antihypertensive medication. Their action is to inhibit the reabsorption of sodium and chloride in the distal tubules. They also increase potassium and bicarbonate excretion and decrease calcium excretion and uric acid retention. Thiazides do not affect normal blood pressure, but long-term use may cause hyponatremia.

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Renin inhibitors These drugs act within the renin-angiotensin system (RAS). RAS is a hormone system that is important for regulation of blood pressure, electrolyte homeostasis, and vascular growth.

Acute and chronic stages Acute stage This stage is when patients experience a stressor or the effects of an illness that raises the blood pressure, fluctuating between stage 1 and 2. Therapy may include remedies with cardioprotective properties while the patient recovers back to normal blood pressure levels or regular life. Nutrients, one or all: • Alpha lipoic acid (ALA) • Cod liver oil • Coenzyme Q-10 • Chromium • Magnesium Herbal formulas, one to three: • Modified yang hyperactivity check with 7-drugs formula • Modified liver subduing and wind stopping formula • Modified BP-reducing decoction • Modified qi replenishing and yin nourishing formula • Modified cardiotonic formula

Chronic Stage Remedies from the acute stage can be effective and must be reduced or eliminated if the blood pressure has sustained increases, with trending patterns that assume to threaten life, or tumors and other health conditions that may necessitate surgical intervention. This includes stage 2 hypertension, when high blood pressure can affect the eyes, overall well-being, aldosterone production, and the kidneys. • When the eyes are affected, patients risk developing an increase in intraocular pressure and glaucoma. Areas of the eyes of concern include the retina, choroid, and optic nerve. • ACEIs may reduce the damage of retinopathy beyond the reduction caused by lowered blood pressure. • When overall well-being is threatened because of elevated blood pressure, paroxysmal hypertension, palpitations, headache, pallor, and perspiration, the physician may be concerned

Chapter 4 Acute, chronic, recovery, and prevention stages

about any medication effects and also suspect pheochromocytoma. The presence of a tumor may necessitate testing plasma and urine for catecholamines and metabolites. When primary hyperaldosteronism is suspected, hypertension is increasingly becoming resistant with potassium depletion or despite potassium and bicarbonate levels being within range, certain drugs may be indicated. • Hydrochlorothiazide or furosemide in combination with either spironolactone or amiloride corrects hypokalemia and normalizes the blood pressure. • A vasodilator or a beta-blocker for better control of hypertension. • A CT scan may help localize an adrenal mass, but if the results are inconclusive, adrenal venous sampling can be performed to test for aldosterone and cortisol levels. • Patients with an adrenal mass who are considered a poor surgical risk can be treated for salt and water depletion. Certain health symptoms manifest, which may be due to being affected by medication: • Hypokalemia, a response to taking a thiazide • Metabolic alkalosis • For patients whose kidney functioning is affected, causing sustained blood pressure elevations, some medications may be avoided in bilateral renal artery stenosis or stenosis found in one kidney. • A diuretic with an ACEI is often prescribed. • Calcium antagonists have a glomerular vasodilatory effect, are effective in renal artery stenosis, and do not compromise renal function.

Recovery and prevention stages A strategy must be set up to reduce the effects of hypertension, which includes adopting a sustainable lifestyle, earlier blood pressure detection, and understanding of appropriate treatment hierarchies from prevention to surgical intervention leading toward mortality. Even a small reduction in diastolic blood pressure by 2 mmHg can decrease the risk of stroke by 15% and the risk of coronary heart disease by 6%. In the western medicine community in the United States, certain groups are considered highrisk, and strategies for them should include a closer watch and care for their overall health. Those groups include patients with a family history of hypertension; obesity and weight gain with physical inactivity; excessive consumption of sugar, sodium, and

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alcohol; those with a black (African) ancestry; and physical inactivity. Prevention of hypertension may be achieved by the following interventions: • Weight control techniques • Increased physical activity • Moderate sodium intake • Reduced alcohol intake • Increased potassium intake • A diet rich in fruits and vegetables • Meat and dairy consumers can enjoy lean meats, fish, and lowfat dairy products. Nutrients: According to mild symptoms and associated with deficiencies seen in laboratory tests • ALA • Cod liver oil • Coenzyme Q-10 • Chromium • Magnesium • Potassium • Selenium • Vitamin B6 and folic acid • Vanadium • Zinc Herbal formulas, one to three: • Modified gambirplant branch formula • Modified yang hyperactivity check with 77-drugs formula • Modified liver subduing and wind stopping formula • Modified BP-reducing decoction • Modified qi replenishing and yin nourishing formula • Modified cardiotonic formula

Further reading Osborn JW, Banek CT. Catheter-based renal nerve ablation as a novel hypertension therapy: lost, and then found, in translation. Hypertension. 2018;71(3):383e388. Jeffrey S. New ACC/AHA hypertension guidelines make 130 the new 140. Medscape Medical News. November 13, 2017; Accessed: November 18, 2017. Qaseem A, Wilt TJ, Rich R, et al. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American college of physicians and the American academy of family physicians. Ann Intern Med. 2017;166(6): 430e437.

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Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1e87. Briasoulis A, Bakris GL. Current status of renal denervation in hypertension. Curr Cardiol Rep. 2016;18(11):107. Forman JP, Scheven L, de Jong PE, Bakker SJ, Curhan GC, Gansevoort RT. Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension. Circulation. 2012;125(25): 3108e3116. American Diabetes Association. Standards of medical care in diabetes 2011. Diabetes Care. 2011;34(Suppl 1):S11eS61. Aburto NJ, Hanson S, Gutierrez H, Hooper L, Elliott P, Cappuccio FP. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;3(346):f1378. https:// doi.org/10.1136/bmj.f1378. Ried K, Sullivan T, Fakler P, Frank OR, Stocks NP. Does chocolate reduce blood pressure? A meta-analysis. BMC Med. 2010;8:39. Fahey T, Schroeder K, Ebrahim S. Interventions used to improve control of blood pressure in patients with hypertension. Cochrane Database Syst Rev. 2006:CD005182. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(9): 1273e1284. Bakris G, Briasoulis A, Dahlof B, et al. Comparison of benazepril plus amlodipine or hydrochlorothiazide in high-risk patients with hypertension and coronary artery disease. Am J Cardiol. 2013;112(2):255e259. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013. Wood S. JNC 8 at Last! Guidelines Ease up on BP Thresholds, Drug Choices. Heartwire; December 18, 2013. O’Riordan M. Spironolactone Provides Benefit in Resistant Hypertension, Small Study Shows. serial online. Medscape Medical News; June 17, 2013. Tsimihodimos V, Gonzalez-Villalpando C, Meigs JB, Ferrannini E. Hypertension and diabetes Mellitus: coprediction and time trajectories. Hypertension. 2018; 71(3):422e428. Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3). Ogihara T, Saruta T, Rakugi H, et al. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 2010;56(2):196e202. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged 75 years: a randomized clinical trial. JAMA. 2016;315(24):2673e2682. Altschul DM, Wraw C, Der G, Gale CR, Deary IJ. Hypertension development by midlife and the roles of premorbid cognitive function, sex, and their interaction. Hypertension. 2019;73(4):812e819. https://doi.org/10.1161/ HYPERTENSIONAHA.118.12164.

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Braunthal S, Brateanu A. Hypertension in pregnancy: pathophysiology and treatment. SAGE Open Med. 2019;7. https://doi.org/10.1177/ 2050312119843700, 2050312119843700. Published 2019 Apr 10. Bravo MA, Batch BC, Miranda ML. Residential racial isolation and spatial patterning of hypertension in Durham, North Carolina. Prev Chronic Dis. 2019;16:E36. https://doi.org/10.5888/pcd16.180445. Published 2019 Mar 28. Butrous G. Schistosome infection and its effect on pulmonary circulation. Glob Cardiol Sci Pract. 2019;2019(1):5. https://doi.org/10.21542/gcsp.2019.5. Published 2019 Mar 31. Choi WS, Lee JW, Lee JY, Kim KY, Myong JP, Lee WC. The effect of special medical examination for night shift workers and follow-up management against hypertension. Int J Environ Res Public Health. 2019;16(5):719. https:// doi.org/10.3390/ijerph16050719. Published 2019 Feb 28. Cuevas S, Villar VAM, Jose PA. Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation. Pharmacogenomics J. 2019; 19(4):315e336. https://doi.org/10.1038/s41397-019-0082-4. Eze IC, Bassa FK, Esse C, et al. Epidemiological links between malaria parasitaemia and hypertension: findings from a population-based survey in rural Côte d’Ivoire. J Hypertens. 2019;37(7):1384e1392. https://doi.org/ 10.1097/HJH.0000000000002071. Hua Q, Fan L, Li J, Joint Committee for Guideline Revision. 2019 Chinese guideline for the management of hypertension in the elderly. J Geriatr Cardiol. 2019;16(2):67e99. https://doi.org/10.11909/j.issn.16715411.2019.02.001. Jiang Y, Li Q, Jia M, Yan Z. PPARd: A Potential Therapeutic Target for the Treatment of Metabolic Hypertension. Int J Hypertens. 2019;2019:7809216. https://doi.org/10.1155/2019/7809216. Published 2019 Apr 3. Jongen VW, Lalla-Edward ST, Vos AG, et al. Hypertension in a rural community in South Africa: what they know, what they think they know and what they recommend. BMC Public Health. 2019;19(1):341. https://doi.org/10.1186/ s12889-019-6642-3. Published 2019 Mar 25. Kokubo Y, Padmanabhan S, Iwashima Y, Yamagishi K, Goto A. Gene and environmental interactions according to the components of lifestyle modifications in hypertension guidelines. Environ Health Prev Med. 2019; 24(1):19. https://doi.org/10.1186/s12199-019-0771-2. Published 2019 Mar 11. Mikolajczyk TP, Guzik TJ. Adaptive immunity in hypertension. Curr Hypertens Rep. 2019;21(9):68. https://doi.org/10.1007/s11906-019-0971-6. Published 2019 Jul 18. Overwyk KJ, Zhao L, Zhang Z, Wiltz JL, Dunford EK, Cogswell ME. Trends in blood pressure and usual dietary sodium intake among children and adolescents, National Health and Nutrition Examination Survey 2003 to 2016. Hypertension. 2019;74(2):260e266. https://doi.org/10.1161/ HYPERTENSIONAHA.118.12844. Rosenzweig EB, Abman SH, Adatia I, et al. Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management. Eur Respir J. 2019;53(1):1801916. https://doi.org/10.1183/ 13993003.01916-2018. Published 2019 Jan 24. Schutte AE, Gona PN, Delles C, et al. The African prospective study on the early detection and identification of cardiovascular disease and hypertension (African-PREDICT): design, recruitment and initial examination. Eur J Prev Cardiol. 2019;26(5):458e470. https://doi.org/10.1177/2047487318822354.

Chapter 4 Acute, chronic, recovery, and prevention stages

Tanase DM, Gosav EM, Radu S, et al. Arterial hypertension and interleukins: potential therapeutic target or future diagnostic marker? Int J Hypertens. 2019;2019:3159283. https://doi.org/10.1155/2019/3159283. Published 2019 May 2. Taylor EB, Wolf VL, Dent E, Ryan MJ. Mechanisms of hypertension in autoimmune rheumatic diseases. Br J Pharmacol. 2019;176(12):1897e1913. https://doi.org/10.1111/bph.14604. Victor RG, Li N, Blyler CA, et al. Nocturia as an unrecognized symptom of uncontrolled hypertension in black men aged 35 to 49 years. J Am Heart Assoc. 2019;8(5):e010794. https://doi.org/10.1161/JAHA.118.010794. SPRINT MIND Investigators for the SPRINT Research Group, Williamson JD, Pajewski NM, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321(6):553e561. https://doi.org/10.1001/jama.2018.21442. Yao Q, Liu C, Zhang Y, Xu L. Health-related quality of life of people with selfreported hypertension: a national cross-sectional survey in China. Int J Environ Res Public Health. 2019;16(10):1721. https://doi.org/10.3390/ ijerph16101721. Published 2019 May 16. Yu BB, Zhi H, Zhang XY, et al. Mitochondrial dysfunction-mediated decline in angiogenic capacity of endothelial progenitor cells is associated with capillary rarefaction in patients with hypertension via downregulation of CXCR4/JAK2/SIRT5 signaling. EBioMedicine. 2019;42:64e75. https://doi.org/ 10.1016/j.ebiom.2019.03.031. Zilbermint M, Hannah-Shmouni F, Stratakis CA. Genetics of hypertension in african americans and others of african descent. Int J Mol Sci. 2019;20(5): 1081. https://doi.org/10.3390/ijms20051081. Published 2019 Mar 2.

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II SECTION

Anti-arrhythmics

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5 Anti-arrhythmic Agents Chapter Objectives: 1. Understand the use of antiarrhythmic drugs and some concerns about toxicity and side effects. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of antiarrhythmic drugs. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with antiarrhythmic drugs. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.

Background Traditional Chinese medicine (TCM) physicians who encounter or are referred a patient with dysrhythmias on prescribed drugs need to keep a close observation of the condition and consider a broad differential diagnosis. Differential diagnosis includes obvious conduction disturbances, ischemia, abnormal shape of the cardiac structure, and evidence of drug toxicity. TCM physicians need to become very familiar with diagnostic results including imaging and lab findings. These findings can point to the need for further study using interventional techniques. These techniques include electrocardiographic profiling, catheter ablation, and the implantable cardioverter-defibrillator, which are often a necessary part of western medicine treatment for serious conditions such as supraventricular and ventricular tachycardia. The challenge is to find an early point in the patient’s health where prevention using herbs and nutrition might educate and help a growing population of patients who would later potentially manifest underlying heart failure. It is important to note that by the time arrhythmias are sustained and diagnosed and the adverse health condition is escalating, herbal medicine will be Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00005-6 Copyright © 2020 Elsevier Inc. All rights reserved.

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contraindicated. The reason is because prescribing them will not generally suffice to rescue the health of the patient. When antidysrhythmic drugs need to continue for treating and suppressing life-threatening dysrhythmias, herb and drug interactions need not be a complicating factor, nor should it constitute an uncertainty in prognosis following electrocardiographic profiling, catheter ablation, and the implantable cardioverter-defibrillator. Patients who visit physicians and practitioners of TCM are looking for natural solutions, yet they often do so at a complicated point in their health condition. Patients may be in noncompliance with the current diagnosing and prescribing physician by manipulating medication use. After receiving a thorough intake and discovering the patient has arrhythmia, it is best to obtain medical records from their physician, which will detail the health progress and what medications the patient has been prescribed. Many diagnosed patients complain that the reason they seek natural medicine is because of the reducing quality of life after taking medications. Managing patients on prescribed medication for chronic and complicating dysrhythmia includes monitoring for sudden death. For this reason alone, it may be necessary to refer the patient back to their main physician to avoid liability. Considering the side effects and toxicity of many of these drugs range from symptomatic problems presented in routine clinical visits to life threatening consequences, it is best to understand how dysrhythmic drugs work. Further, it is crucial to understand what symptoms could be presented in the clinic as part of routine management, what should be referred out or back to a specialist, and what constitutes emergency alert to first responders. The main reasons for study of arrhythmia are for the purposes of realizing what compromised patients will often face in the future and how to help patients avoid such with careful measures during early prevention and recovery stages.

History and physical examination History Before considering whether herbal medicine could be indicated for a patient with arrhythmia, it is best to understand the common history of patients who are prescribed antiarrhythmic drugs. TCM physicians must differentiate between the disease and side effects of the prescribed drugs. Information needed to initiate clarity includes but is not limited to: • What symptoms prompted the need for prescribing the drug • For what the prescribed drugs were indicated • What dosing has been recommended and set

Chapter 5 Anti-arrhythmic Agents

• The duration of taking the prescribed drug and the therapeutic target • What new drugs have recently been added • Patient compliance: overmedicating worsening symptoms, discontinuing doses when feeling better, and taking any unreported nonprescription remedies and drugs

Physical examination with electrocardiography Clinical presentations will most likely involve general symptoms and toxicity with associated electrocardiographic abnormalities. • Anticholinergic syndromes: Procainamide, disopyramide, quinidine • CNS symptoms: Quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, propafenone • Dermatologic: Procainamide, propafenone • Endocrine dysfunction: Amiodarone, quinidine, and disopyramide • Heart failure: Disopyramide, flecainide, propafenone, sotalol, procainamide • Hypotension: Quinidine, procainamide, amiodarone, dronedarone, lidocaine, mexiletine, flecainide, propafenone • Hematology/oncology: Amiodarone, procainamide • Pulmonary/autoimmune: Amiodarone, procainamide • Seizures (acute toxicity): Quinidine, procainamide, lidocaine, mexiletine, flecainide, propafenone Electrocardiographic changes are as follows: • QRS widening: Quinidine, procainamide, disopyramide, flecainide, propafenone, amiodarone, dronedarone • PR prolongation: Procainamide • QTc prolongation: Amiodarone, procainamide, quinidine, disopyramide, dronedarone, sotalol, dofetilide, flecainide, propafenone • Ventricular arrhythmia: Procainamide • Torsades de pointes: Dofetilide, sotalol, quinidine, procainamide, disopyramide

Common symptoms associated with taking common antiarrhythmic agents Adenosine Symptoms that resolve quickly without additional treatment: • Chest pressure • Headache and light-headedness • Dyspnea • Skin flushing

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Electrocardiography (ECG) • Transient asystole, the treatment goal • Developing bradycardia, AV block, or sinus arrest • Atrial fibrillation Amiodarone This drug generally causes several types of side effects, cytotoxicity, immunological problems, and pulmonary toxicity. Direct reactions including bradyarrhythmias and asystole due to prolonged use over time. Generally, symptoms include: • Endocrine problems: hyperthyroidism or hypothyroidism • Central nervous system problems: tremors and dizziness, cognitive fogginess, sleep problems • Dermatological problems: bluish skin discoloration and sensitivity to sunlight • Ophthalmologic: optic neuritis and neuropathy, vision loss Pulmonary toxicity effects include: • Pulmonary fibrosis • Bronchiolitis obliterans • Pleural effusion • Chronic interstitial pneumonitis • Rales and crackles without clubbing Other symptoms of pulmonary toxicity: • Dyspnea • Cough • Fever • Hemoptysis • Malaise • Weight loss • Acute diffuse pneumonitis • Respiratory failure resembling acute respiratory distress syndrome • Hepatotoxicity: jaundice • Hyper/hypothyroidism • Photosensitivity ECG • Prolonged PR and QTc intervals • Sinus bradycardia • Ventricular dysrhythmias • AV block Beta blockers This drug is a popular drug for male sexual virility. It is also prescribed for hyperthyroid and other expanded uses. It is known to

Chapter 5 Anti-arrhythmic Agents

cause hypoglycemia, hypotension, bradycardias, and other types of arrhythmias. Calcium channel blockers See Chapter 12. Dronedarone This drug generally causes several types of side effects. Direct reactions include brady-arrhythmias and asystole due to prolonged use over time. Some patients experience pulmonary toxicity effects, which include: • Pulmonary fibrosis • Bronchiolitis obliterans • Pleural effusion • Chronic interstitial pneumonitis • Bradycardia Other symptoms: • Shortness of breath • Coughing • Crackles and rales without clubbing • Hepatoxicity: jaundice ECG • Prolonged QTc interval and hypotension Disopyramide This drug causes ventricular problems and other symptoms similar to heart failure, and interferes with diabetes medication. Clinical presentations include: • Edema/bloating • Dyspnea and rales • Severe fatigue/exercise intolerance • Constipation • Nausea • Dry mouth • Blurred vision and increased ocular pressure in glaucoma • Peripheral edema, bloating, and urinary retention • Dry skin • Headache Physical exam • Increased jugular venous distention, peripheral edema, and rales ECG • Prolonged PR and QTc intervals that may progress to torsades de pointes

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Flecainide This drug causes symptoms with CNS effects, symptoms similar to heart failure, and possibly cardiomyopathy. Clinical presentations include: • Nausea and dizziness • Blurred vision • Confusion • Headache Severe CNS toxicity • Seizures • Paranoid psychosis and hallucinations • Stroke-like limb movement and gait Congestive heart failure • Dyspnea on exertion • Lethargy • Peripheral edema Cardiomyopathy • Dysrhythmia • Cardiac arrest ECG • Cardiotoxicity: wide QRS complex, prolonged PR and QTc intervals, first- or second-degree heart block • Bradycardia and hypotension • AV block • Atrial ventricular conduction • Ventricular fibrillation • Prolonged ventricular depolarization that increases torsades de pointes • ST elevation in lead V1 characteristic of Brugada syndrome (also used to diagnose suspected Brugada syndrome) Lidocaine and mexiletine These drugs cause CNS toxicity with initial signs being seizures followed by coma and respiratory arrest. Other CNS symptoms and clinical presentations include: • Vision changes • Nausea and vomiting • Tinnitus • Tongue numbness • Hallucinations • Drowsiness • Insomnia • Seizures • Dizziness/light headedness • Personality changes • Memory problems

Chapter 5 Anti-arrhythmic Agents

• • • • •

Dysphoria Ataxia Depression Agitation Coma

Lidocaine • Cardiotoxicity: sinus arrest, atrioventricular block, hypotension, and cardiac arrest • Overdose: prolonged QRS, PR, and QT intervals Mexiletine • Cardiotoxicity: bradycardia, AV block, torsades de pointes, and ventricular fibrillation Procainamide This drug can cause drug-induced systemic lupus erythematosus (SLE) syndrome in both males and females. Symptoms are characterized by Raynauds phenomenon, skin rash, vasculitis, and arthralgia. In addition, patients on this medication often present at a dentist’s office with complaints of bleeding gums; at their physician’s office with a mix of flu-like symptoms of fever, sore throat, nausea, vomiting, and diarrhea; and may be monitored by the cardiologist for gastro-intestinal bleeding, hypotension, and peripheral vasodilation. Other symptoms include: • Bitter mouth taste • Insomnia • Headache and dizziness • Psychosis involving auditory and visual hallucinations • Depression Acute cardiotoxicity may result in any of the following: • Prolonged QT interval • Torsades de pointes • Left ventricular dysfunction • Ventricular tachycardia • Premature ventricular contractions • Atrioventricular (AV) Propafenone This drug may cause drug-induced SLE syndrome in both males and females and definitely causes symptoms of worsening heart failure, gastrointestinal symptoms, and CNS symptoms that are dose dependent. Clinical presentations include: Heart failure • Dyspnea and breathlessness • Edema

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• Common adverse effects include alteration in taste, blurred vision, and dizziness Gastrointestinal • Nausea and vomiting • Constipation CNS • Nausea and dizziness • Bitter mouth taste • Blurred vision • Seizures • Ataxia ECG • Cardiotoxicity: wide QRS complex and sinus bradycardia Quinidine This drug acts on the potassium channels and may cause druginduced SLE syndrome in both males and females. It also can cause immune-mediated hematologic reactions including side effects, acute and chronic toxicity symptoms. Clinical presentations include: • Blurred vision • Dry mouth • Urinary retention • Peripheral vasodilation • Syncope hypotension • Syncope Acute and chronic toxicity symptoms • Cinchonism • Altered mental status • Rash • Fever • Anaphylaxis • Hemolytic anemia, thrombocytopenia, and leukopenia ECG • Cardiotoxicity: wide QRS, prolonged PR and QTc intervals Sotalol Clinical presentations include: • Palpitations and chest pain • Light-headedness and syncope, possibly torsades de pointes • Fatigue and body weakness • Insomnia • Headache • Dyspnea, shortness of breath, and wheezing

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• Nausea with mild diarrhea, nausea, and vomiting ECG • Cardiotoxicity: prolonged QTc interval • Ventricular arrhythmias

Differential diagnosis Lab tests that may be helpful for certain clinical presentations: • Women of childbearing age: pregnancy test to determine drug and herb contraindication • Febrile disease conditions: lumbar puncture, urine and blood cultures • Overdose and poisoning: ECG, acetaminophen and salicylate (aspirin) screen • Serum and electrolyte analysis • CNS infection: lumbar puncture • Arterial blood gas analysis

Clinical workup • CT scan or MRI: altered mental status • ECG: clinical manifestations and suspected overdose

Traditional Chinese medicine Monitor patients for any increase in heart rhythm activity and discontinue when a patient is prescribed medicine such as warfarin and digoxin.

Nutritional supplements Cod liver oil Nutritional constituents: Vitamins A, D, and omega-3 fatty acids (fish oils, flax seed, primrose, borage, and flaxseed oils) Benefits: Reduces cardiometabolic risk factors, protects sudden cardiac death after myocardial infarction, reduces raised plasma triglycerides, reduces blood pressure, and ameliorates atherogenic effects Caution: High doses required for reduction of blood pressure may have side effects.

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Coenzyme Q10

Traditional Chinese medicine formulas for arrhythmia Herbal medicine

Action

An xin ning xin formula Fu mai decoction Shen fu decoction Si ni decoction Wen dan decoction Ling gui shu gan decoction Xue fu zhu yu decoction Tao hong si Wu decoction Zhi gan cao decoction

Soothes the spirit Qi and blood deficiency Recovers after an illness, warms yang Warms coldness Regulates qi and transforms phlegm Phlegm retention Blood stagnation and stasis Invigorate blood Recovers from illness, regulates heart functioning Nourishes blood

Gui pi decoction

Benefits: Heart, muscle, liver, and lungs; improves glycemic index, myocardial energy Caution: Body stores are reduced when glyburide is prescribed for diabetes.

L-carnitine Nutritional constituents: Amino acid synthesized from lysine and methionine Benefits: Mitochondrial energy in the cells of the heart, muscle, liver, and lungs Caution: May cause headache due to blood pressure problems with inappropriate dosing, blood sugar may be reduced too much when taken with medication

Calcium chloride Benefits: Drives calcium into the cells to reverse hypotension and improve cardiac conduction defects, regulates action potential threshold for nerve and muscle performance

Chapter 5 Anti-arrhythmic Agents

Magnesium sulfate Benefits: Used in magnesium deficiency, treatment of torsades de pointes, and refractory ventricular fibrillation Note: Potassium and magnesium should be given with caution by parenteral administration in patients taking drugs that prolong QTc intervals.

Sodium bicarbonate Benefits: Must be given as a bolus intravenously in patients presenting in the clinic with cardiotoxicity from antidysrhythmic medication, with widening QRS interval Continue to run the 12-lead ECG during administration to monitor QRS. Caution: Serum pH should be monitored during treatment for balancing.

Pharmaceutical drugs Cardiac action potentials Phase Phase Phase Phase

0 1 2 3

Influx of Sodium Ions Inactivation of the sodium channel Voltage plateau causes the opening of calcium channels Repolarizing of potassium ions

Antidysrhythmic drugs are often categorized using the VaughaneWilliams classification system, which is based on their mechanism of activity. The VaughneWilliams classes are as follows: • Class I: Sodium channel blockers • Class II: Beta-adrenergic blockers • Class III: Potassium channel blockers • Class IV: Calcium channel blockers • Class V: Other or unknown mechanism of action: these include the actions of magnesium, digoxin, and adenosine.

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Class I: Sodium channel blockers

• • • • •

Class IA agents

• •

Class IB agents

• •

• • Class IC agents • • • • • Class II: Beta-adrenergic • blockers • Class III: Potassium • channel blockers • • Class IV: Calcium channel • blockers •

Reduce depolarization rate, which slows and reduces phase 0 Provide local anesthesia by inhibiting neuronal cells Inhibit depolarization in atrial, ventricular, and Purkinje myocytes Decrease conduction velocity and automaticity Are categorized into A, B, or C subclasses according to the degree and effects of blocking of sodium channels and repolarization Prolong both the QRS and QTc intervals Prolong the repolarization and action potential phases through blocking potassium channels Slow cardiac conduction Do not prolong the QRS interval; shorten the duration of the action potential phases Depress cardiac conduction in ischemic cells Bind to the sodium channel in its inactivated state Prolong the QRS interval; decrease the rise rate of phase 0 of the action potential Have little effect on action potential duration Depress cardiac conduction Bind to sodium channels in the active state Are slow to release from sodium channels Block the opening of calcium channels Block the proarrhythmic effects of catecholamines Lead to prolonged QTc intervals Delay repolarization by blocking potassium channels Have very little effect on sodium channels Slow sinoatrial node pacemaker cell Slow atrioventricular conduction by blocking L-type voltage-gated calcium channels

Class IA antidysrhythmics Disopyramide Sodium and potassium channel blocker and muscarinic antagonist. Indications: Atrial and ventricular dysrhythmias Metabolism: Metabolized by the liver (CYP3A4) with 40%e60% excreted by the kidneys so use with caution in renal failure Procainamide Sodium and potassium channel blocker and prolong the action potential duration of ventricular myocytes and Purkinje fibers.

Chapter 5 Anti-arrhythmic Agents

Indications: Supraventricular or ventricular dysrhythmias Metabolism: Metabolized in the liver by acetylation into a metabolite that prolongs the action potential with drug and metabolite excreted by the kidneys Quinidine Sodium, potassium channel, alpha adrenergic, and muscarininc receptor blocker Indications: Atrial and ventricular dysrhythmias and Brugada syndrome Metabolism: Hepatic elimination is 60%e80% and renal elimination is 20%e40% so use with caution in hepatic or renal diseases.

Class IB antidysrhythmics Lidocaine Sodium channel blocker and leads to phase 0 depolarization reduction rate and shortens action duration of Purkinje fibers. Indications: For ventricular dysrhythmias and as a local anesthetic; previously prevented dysrhythmias after heart attack (amiodarone is now used for this purpose and should not be taken with lidocaine). Metabolism: Hepatic metabolism by CYP3A4 into an active metabolite Mexiletine Sodium channel blocker and leads to phase 0 depolarization reduction rate and shortens action duration of Purkinje fibers and prevents delayed ventricular repolarization and torsades de pointes in long QT syndrome. • Indications: Ventricular dysrhythmias and pain in peripheral neuropathy • Metabolism: After absorption in the small intestine, it is metabolized by liver CYP2D6 at 90%, eliminated unchanged by the kidneys at 10%, so use with caution in hepatic and renal disease.

Class IC antidysrhythmics Flecainide Sodium channel blocker, has negative inotropic effects and slows conduction in all cardiac fibers.

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• Indications: Paroxysmal atrial fibrillation and ventricular dysrhythmias and used to help diagnose and treat congenital Brugada and LQT3 syndromes • Metabolism: Hepatic metabolism CYP2D6 at 75% and renal metabolism at 25% so used with caution in hepatic and renal diseases. Propafenone Sodium and calcium channel blocker. Indications: Atrial fibrillation and life-threatening ventricular dysrhythmias Metabolism: Hepatic metabolism by CYP2D6, CYP3A4, and CYP1A2

Class III antidysrhythmics Amiodarone Sodium, L-type calcium potassium channel or beta receptor delayer or blocker and prolongs refractory periods of cardiac tissue. Indications: Supraventricular and life-threatening ventricular dysrhythmias Metabolism: Hepatic metabolism by CYP3A4 to an active metabolite and mostly excreted in bile Dronedarone Sodium, L-type calcium potassium channel and beta receptor delayer or blocker, prolongs refractory periods of cardiac tissue and inhibits alpha1 receptors. Indications: Atrial and ventricular dysrhythmias and sinus rhythm for atrial flutter or fibrillation Metabolism: Hepatic metabolism by CYP3A4 to active and inactive metabolites Sotalol Nonselective beta-adrenergic antagonist, potassium channel blocker, prolongs the action potential and effective refractory period Indications: Ventricular dysrhythmias, atrial fibrillation, AV tachycardia Metabolism: 90%e100% bioavailability and absorption rate, no metabolism, used with caution in renal disease so creatinine clearance is necessary and excreted unchanged by kidneys

Chapter 5 Anti-arrhythmic Agents

Class V antidysrhythmics Adenosine Induces a short-duration heart block and atrial action potential, polarizes myocyte membrane potential, slows AV node conduction, and increases potassium conduction. Indications: Given for supraventricular tachycardia after failure of vagal maneuver Metabolism: Intracellular metabolism

Alpha/beta-adrenergic agonists Norepinephrine • Increases cardiac output, blood pressure, and heart rate • Strong beta 1 and alpha-adrenergic effects with moderate beta 2 effects • Decreases renal perfusion • Decreases pulmonary vascular resistance

Beta 1/Beta 2 Adrenergic agonists Isoproterenol • Treats torsades de pointes if treatment with magnesium fails • Treats ventricular tachycardia or fibrillation with Brugada syndrome

Anticonvulsants These drugs include benzodiazepines, are CNS (limbic and reticular formation) depressants by increasing the action of gamma aminobenzoic acid, which is a major inhibitory neurotransmitter. Diazepam • Treats emotional irritability or seizures • Accumulates active metabolites that may prolong sedation Lorazepam • Remains in the central nervous system longer than diazepam • Treatment of status epilepticus • Administered intramuscularly if vascular access cannot be obtained Midazolam • Treatment of status epilepticus • Takes three times longer than diazepam to achieve results • Administered intramuscularly if vascular access cannot be obtained

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Acute and chronic stages As already inferred earlier, it is important to get a patient in the prevention stage when drug use may not be necessary and herbal medicine could be indicated. However, when patients visit TCM practitioners, they usually do so at complicated periods of western medicine treatment. These periods are when the medication has become a problem due to side effects and toxicity and when patients, who may or may not be in compliance, are weaning themselves off the medications and are experiencing adverse effects that they hope can be alleviated using natural remedies.

Acute stage The first concern is about patients taking selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). They may have clearance from the treating doctor to be removed from taking the drugs. These physicians usually suggest around 2 weeks to wean off medications without any trouble. Patients will present to the clinic for herbal medicines during this time to help alleviate withdrawal symptoms. The main complaints include weakness, tiredness, body aches, panic attacks, brain fog, and a phenomenon called “brain zaps.” The brain zaps are reported as a sensation similar to electrical shock that surges from the head to toes and may cause a stun that lasts from a few seconds to a few minutes. Often these patients are sent home from emergency visits without medication and a referral back to the attending physician who denies the withdrawal and effects. Patients may present for Chinese herbal medicines and nutritional supplements. Patients should be evaluated closely and must be upfront about medication use. Some patients are following social trends that suggest continuing to fill drug prescriptions for up to 18e24 months for the purposes of creating alternative weaning schedules. The weaning schedules are for curtailing or alleviating reported withdrawal symptoms such as brain zaps and others. These patients will open capsules to count out granules and titrate dosages over time, usually between 6e24 months of continued prescription filling. Under very close supervision, if it is indicated that patients taking SSRIs and MAOIs can take a course of natural medicines, caution about any with serotonin activity and monitor for mood and behavior problems that could result in emergency room visits. The second concern is about patients who present to the clinic with symptoms they wish treated with TCM, and are currently taking prescription drugs that have serious side effects or toxicities, or patients have overmedicated themselves in the attempt

Chapter 5 Anti-arrhythmic Agents

to alleviate worsening symptoms when scheduling a visit with their physician is not possible. For suspected antidotes to a suspected overdose presenting in the clinic: • Adsorbent antidotes for overdose: activated charcoal • Make the patient comfortable and dispatch first responder emergency services Patients who present to their physician’s office may be given the following antidotes: • Serotonin antagonists: cyproheptadine • Sedatives and anticonvulsants: lorazepam, diazepam, midazolam • Antihypertensives: nitroprusside, esmolol When patients are experiencing reversible arrhythmias as a symptom associated with a temporary non-life-threatening illness, the following can help to control blood sugar and while weaning completely off of medications.

Nutrients: one or all • • • • • • • •

Cod liver oil L-carnitine

Coenzyme Q-10 Chromium Magnesium Potassium Vitamin B6 L-5-hydroxytryptophan (5-HTP)

Chronic stage This stage is for patients experiencing mild symptoms that have the potential for heart failure in the future. The patient may be able to fortify drug treatment with occasional hepatic and renal protecting herbal formulas, remedies that build blood and calm emotions, and remedies that rescue health after a bed-ridden illness or temporary hospitalization, not associated with sudden death risk or asystole. Nutrients: According to mild symptoms and associated with deficiencies seen in laboratory tests or for comfort measures • Cod liver oil • L-carnitine • Coenzyme Q-10 • Chromium • Magnesium

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• Potassium • Vitamin B12, used to relax mood and help build blood • 5-HTP, used to relax mood and reduce brain zaps with vitamin B12

Herbal formulas 1e3 • • • • • • • • • •

An xin ning xin formula Fu mai decoction Shen fu decoction Si ni decoction Wen dan decoction Ling gui shu gan decoction Xue fu zhu yu decoction Tao hong si wu decoction Zhi gan cao decoction Gui pi decoction

Further reading Somberg JC, Preston RA, Ranade V, Cvetanovic I, Molnar J. Gender differences in cardiac repolarization following intravenous sotalol administration. J Cardiovasc Pharmacol Ther. 2012;17(1):86e92. Nair M, George LK, Koshy SK. Safety and efficacy of ibutilide in cardioversion of atrial flutter and fibrillation. J Am Board Fam Med. 2011;24(1):86e92. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 annual report of the American association of poison control centers’ national poison data system (NPDS): 32nd annual report. Clin Toxicol. 2015;53(10):962e1147. Lindquist DE, Rowe AS, Heidel E, Fleming T, Yates JR. Evaluation of the hemodynamic effects of intravenous amiodarone formulations during the maintenance phase infusion. Ann Pharmacother. 2015;49(12):1317e1321. Nacca N, Bhamidipati CM, Yuhico LS, Pinnamaneni S, Szombathy T. Severe amiodarone induced pulmonary toxicity. J Thorac Dis. 2012;4(6):667e670. Neal JM, Mulroy MF, Weinberg GL. American society of regional anesthesia and pain medicine. American society of regional anesthesia and pain medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med. 2012;37(1):16e18. € zbasioglu Y, Coskun F. Hemodialysis as an alternative treatment of Akinci E, Yu mexiletine intoxication. Am J Emerg Med. 2011;29(9):1235.e5e1235.e6. Ellsworth H, Stellpflug SJ, Cole JB, Dolan JA, Harris CR. A life-threatening flecainide overdose treated with intravenous fat emulsion. Pacing Clin Electrophysiol. 2013;36(3):e87ee89. Qamar S, Hassan W, Sra J, Akhtar M, Mortada ME. Abstract 14890: hyponatremia associated with flecainide: case series. Circulation. 2012;126:21. Wozakowska-Kaplon B, Stepien-Walek A. Propafenone overdose: cardiac arrest and full recovery. Cardiol J. 2010;17(6):619e622. Ovaska H, Ludman A, Spencer EP, Wood DM, Jones AL, Dargan PI. Propafenone poisoning–a case report with plasma propafenone concentrations. J Med Toxicol. 2010 Mar;6(1):37e40.

Chapter 5 Anti-arrhythmic Agents

Patsilinakos S, Christou A, Kafkas N, et al. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol. 2010; 106(5):673e676. Jovic-Stosic J, Gligic B, Putic V, Brajkovic G, Spasic R. Severe propranolol and ethanol overdose with wide complex tachycardia treated with intravenous lipid emulsion: a case report. Clin Toxicol. 2011;49(5):426e430. Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with hyperinsulinemic euglycemia therapy and intravenous lipid emulsion. Eur J Emerg Med. 2011;18(2):121e123. French D, Armenian P, Ruan W, et al. Serum verapamil concentrations before and after Intralipid® therapy during treatment of an overdose. Clin Toxicol. 2011;49(4):340e344. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol. 2011;49(9):801e809. Martindale JL, Brown DFM. Rapid Interpretation of ECGs in Emergency Medicine: A Visual Guide. Lippincott Williams and Wilkins; 2012. Williams EM. Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol. 1992;32:964e977. Lim YP, Lin CL, Lin YN, et al. Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts. PLoS One. 2015;10(1):e0116960. Benowitz NL. Antiarrhythmic Drugs. Olson KR. Poisoning & Drug Overdose. 6th ed. Mcgraw-Hill; 2012. Piña IL, Oghlakian G. Adverse cardiovascular drug interactions and complications. In: Fuster V, Walsh RA, Harrington RA, eds. Hurst’s the Heart. 13th ed. McGraw-Hill; 2011. Benowitz NL. Quinidine and Other Type Ia Antiarrhythmic Drugs. Olson KR. Poisoning & Drug Overdose. 6th ed. McGraw-Hill; 2012. Trevor AJ, Katzung BG, Kruidering-Hall. Antiarrhythmic drugs. In: Trevor AJ, Katzung BG, Kruidering-Hall, eds. Katzung & Trevor’s Pharmacology: Examination & Board Review. 11th ed. McGraw-Hill; 2015. Ting SM, Lee D, Maclean D, Sheerin NS. Paranoid psychosis and myoclonus: flecainide toxicity in renal failure. Cardiology. 2008;111(2):83e86.

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III SECTION

Anti-thrombotic

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6 Acute, chronic, recovery and prevention stages of PVD and DVT Chapter Objectives 1. Introduce the background and etiology of peripheral vascular disease (PVD) and deep vein thrombosis (DVT). 2. Describe the common history and physical examination. 3. Describe the clinical workup and differential diagnosis. 4. Describe the common treatment approaches in Western medicine. 5. Introduce the traditional Chinese herbal medicine for the root causes and symptoms of PVD and DVT. 6. Introduce nutritional supplements for deficiencies associated with blood circulation. 7. Introduce the pharmaceutical drugs that interact with the expressions and biomechanism failures associated with the movement of blood.

Background Peripheral vascular disease (PVD) and deep vein thrombosis (DVT) are commonly caused by emboli or thrombosis. Thrombosis involves an impairment of the coagulation mechanism, which involves a series of steps that result in a fibrin clot. Under normal conditions the coagulation pathway involves both an intrinsic and extrinsic system that come together at the final level, factor X and Xa. Thrombosis is formed in an earlier step, which ends the cascade. • The extrinsic system: Activated by lipoprotein as a result of injury or trauma • The intrinsic system: Involves circulating plasma factors that promote prothrombin conversion to thrombin factor II, which is necessary for transforming fibrinogen into a fibrin clot Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00006-8 Copyright © 2020 Elsevier Inc. All rights reserved.

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Antithrombotic drugs are commonly used to treat PVD and DVT. Etiology includes phlebitis, autoimmune diseases, blood coagulation disorders, traumatic injury, or surgical complications. It is a condition that manifests through an existing coronary artery disease (CAD) atherosclerosis, which creates insufficient tissue perfusion exasperated by thrombosis or emboli. The following occlusion results in flow stagnation. Limb ischemia, especially in the lower legs, is an acute condition that happens while sitting for long period of time and can become a life-threatening situation. These types of patients may have a history of gait problems when walking, pain in the legs at rest or while sleeping, and circulation problems that may be severe enough to cause blood clots under the skin surface that result in ulceration after bursting. Underlying health conditions can include atrial fibrillation, problems with the heart valves, and possible recent heart attack/myocardial infarction. Acute vascular diseases develop when perfusion is disrupted because of trauma, thrombus, or emboli. When a thrombus is the cause, it occurs commonly in the lower limbs due to: • Atherosclerosis • Aortic dissection • Aneurysm • Hypotension • Sepsis When an embolus is the cause, it commonly occurs in the femoral artery, aorta, iliac, and popliteal arteries due to: • Proximal atheroma • Tumor • Other material Patients who visit a practitioner of traditional Chinese medicine usually are looking for solutions to help with male virility, leg swelling, back pain, and overall energy. Practitioners may find, among other therapeutic principles, that the blood deficiency and stagnation are obvious.

History and physical examination Common health history • • • •

CAD Cerebrovascular disease Renal vascular disease Atrial fibrillation

Chapter 6 Acute, chronic, recovery and prevention stages of PVD and DVT

Noninvasive tests for vascular diseases include the pulse wave velocity and ankle-brachial index (ABI). Risk factors for PVD include: • Smoking • Lipid disorders/obesity • Diabetes mellitus • Psychiatric • Viscous blood • Erectile dysfunction Clinical presentation The area of pain or discomfort is connected to the affected artery: • Aortoiliac disease manifests as pain in the thigh and buttock. • Femoropopliteal disease manifests as pain in the calf. • Distal aorta narrowing manifests Leriche syndrome with symptoms of intermittent claudication, erectile dysfunction, and absence of femoral pulses.

Physical examination Evaluate the arteries for signs of peripheral vascular disease using the “five P’s”: • Pulselessness: limb-threatening ischemia • Paralysis • Paresthesia: limb-threatening ischemia • Pain • Pallor Further assessment: • Assess skin appearance: pigment changes, dry and scaly, erythematous, shiny and atrophic, coldness, mottling, numbness, cyanosis, poorly healing injuries resulting in ulcers or gangrene • Assess nails: usually brittle tips and striation in the nail bed • Check dorsalis pedis artery pulse: absent in 5%e8% of most patients; may be affected by exercise • Check posterior tibial artery pulse: absent in 0.5% of patients; may be affected by exercise • Assess the heart for murmurs or other abnormalities • Test for pulse quality and bruit of carotid, abdominal, and femoral arteries • Perform the Allen test on the hands, which helps provide quality of radial and ulnar arteries • Determine the ABI at the bedside

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• Perform Doppler ultrasonography at the brachial artery and at the posterior tibialis artery • Perform five-level pallor test while the patient is supine on the table: • Level 0: no pallor occurs within 60 seconds • Level 1: pallor occurs 60þ s • Level 2: pallor occurs in less than 60 seconds • Level 3: pallor occurs in less than 30 seconds • Level 4: pallor occurs when the extremity is raised 60 degrees

Differential diagnosis The main laboratory studies: • D-dimer testing: D-dimers are the degradation of fibrin by plasmin. Levels are elevated in sepsis, trauma, hemorrhage, surgical procedures, and cancer. The D-dimer test can be used in care management to detect problems when there are no findings in physical examination or imaging for lower leg edema. Elevated D-dimer tests can also show elevated results 1 month after weaning completely from anticoagulant drugs • Coagulation studies: Evaluate for accelerations of the process. They involve calculating prothrombin and activated partial thromboplastin times • Routine blood tests determine risk: • N-terminal probrain natriuretic peptide • C-reactive protein • Erythrocyte sedimentation rate

Clinical workup Laboratory studies can be ordered at any time, but especially important for diagnosing patients younger than age 50, a family history or genetic predisposition, and skin necrosis caused by warfarin use. • CT venography • Sonography • D-dimer test • MRI • Laboratory studies: homocysteine, protein C, protein S, prothrombin 20210A mutation, ATIII, factor V Leiden, and antiphospholipid antibodies. Presence of deficiencies of any of these factors can create hypercoagulation

Chapter 6 Acute, chronic, recovery and prevention stages of PVD and DVT

Treatment approaches Common approaches used during western medicine treatment • Anticoagulation drugs • Warfarin • Heparin: Low-molecular-weight heparin, unfractionated heparin • Factor Xa inhibitors • Endovascular and surgical interventions • Physical binders: ted hose compression stockings and ambulation

Traditional Chinese medicine

Traditional Chinese medicine formulas for Arrhythmia Herbal medicine

Action

Fu mai decoction Si ni decoction Xue fu zhu yu decoction Tao hong si Wu decoction Zhi gan cao decoction Shen fu decoction Gui pi decoction

Qi and blood deficiency Warms coldness Blood stagnation and stasis Breaks blood stasis, invigorate blood Recovers from illness, regulates heart functioning Recovers after an illness, warms yang Nourishes blood

Nutritional supplements Bioflavonoids Origin: Antioxidants from berries and citrus plants Benefits: Reduces swelling and inflammation and improves blood circulation Caution: Antioxidant use, which may be prohibited in other health conditions

Digestive enzymes Origin: Papain is an enzyme that comes from papaya and bomelain is an enzyme that comes from pineapples

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Benefits: Increases prothrombin time (PTT) to prevent coagulation Caution: Careful use with anticoagulant drugs

Essential fatty acids Origin: Essential fatty acid EPA and DHA from various fish, vegetable, and meat sources Benefit: Antiinflammatory substance prevents platelets from clumping together Caution: Careful use with anticoagulant drugs

Nattokinase Origin: Enzyme created from fermented soybeans Benefits: Enzyme that breaks up blood clots Caution: Working too efficiently with other medicines that break up clots, causing bleeding problems

Lumbrokinase Origin: Enzyme created from fermented soybeans Benefits: Enzyme that breaks up blood clots Caution: Working too efficiently with other medicines that break up clots, causing bleeding problems; may cause mild nausea and bloating

Pharmaceutical drugs The drugs indicated for PVD and DVT are to prevent postthrombotic syndrome, prevent pulmonary embolism (PE), and reduce further health debilitation and morbidity.

Anticoagulants These drugs help prevent thrombolytic vascular occlusion. Many of them reversibly block the active site of factor Xa and affect prothrombin time and platelet function without requiring antithrombin III for activity. They are mostly indicated for use as a prophylaxis, treatment, and preventative of DVT, PE, and venous thromboembolism. • Apixaban: for adult patients undergoing orthopedic surgery • Betrixaban: for hospitalized and restricted/immobile adults at risk for thromboembolic complications

Chapter 6 Acute, chronic, recovery and prevention stages of PVD and DVT

• Dabigatran: prevention of stroke and systemic embolism associated with nonvalvular atrial fibrillation • Edoxaban: reduces the risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation • Fondaparinux sodium: synthetic anticoagulant • Heparin: prevents accumulation of a clot by inhibiting conversion of fibrinogen to fibrin • Rivaroxaban: for adult patients undergoing orthopedic surgery, helps and reduces risk of recurrence of blood clots

Low molecular weight heparins These drugs are prepared by processing heparin to isolate the low molecular weight fragments. The end product is measured out in units designated for inactivation of factor Xa by increasing antithrombin III activity. The measurement is established without checking the PTT or activated partial thrombin time. Doses are given to the patient according to body weight, and treatment usually lasts about 1e2 weeks. They are mostly indicated for the treatment of DVT. • Dalteparin: for DVT treatment • Enoxaparin: for DVT and PE treatment • Tinzaparin: for DVT treatment

Vitamin K antagonists Coumarins interfere with the interaction between vitamin K and dependent coagulation factors II, VII, IX, and X. It is used both as a prophylaxis and treatment of DVT and PE. Doses are adjusted according to patient weight and health condition for maintaining an international normalized ratio of 2-3. • Warfarin

Thrombolytics These drugs help dissolve a thrombus or embolus that passed intact through the fibrinolytic system. They are tissue plasminogen activators given within 24 hours after DVT, PE, ischemic stroke, or myocardial infarction, and as a prophylaxis and management thereafter. Patients are often given heparin and aspirin as well. • Alteplase • Reteplase • Tenecteplase

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Acute and chronic stages Patients may have visited specialists for symptoms that lead to diagnosis or experienced a visit to the emergency room for severe symptoms. During the acute stages in PVD and DVT, patients may have visited specialists for symptoms that lead to diagnosis or experience a visit to the emergency room for severe symptoms. During the chronic stage, CAD condition that manifests through an existing CAD atherosclerosis which creates insufficient tissue perfusion and exasperated by thrombosis or emboli. The following occlusion results in flow stagnation. Limb ischemia, especially in the lower legs, is an acute condition that happens while sitting for long periods of time and can become a life-threatening situation. These types of patients may have a history of gait problems when walking, pain in the legs at rest or while sleeping, and circulation problems that may be severe enough to cause blood clots under the skin surface, which result in ulceration after bursting. Underlying health conditions can include atrial fibrillation, problems with the heart valves, and possible recent heart attack/myocardial infarction. Acute vascular diseases develop when perfusion is disrupted because of trauma, thrombus, or emboli.

Recovery and prevention stages Patients who visit a practitioner of traditional Chinese medicine usually are looking for solutions to help with male virility, leg swelling, back pain, and overall energy. Practitioners may find, among other therapeutic principles, that the blood deficiency and stagnation are obvious. Assisting the patient by balancing yin and yang, qi, and building blood will help them notice marked positive differences in their well-being over time.

Further reading Al-Khudairy L, Flowers N, Wheelhouse R, et al. Vitamin C supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017;3(3):CD011114. https://doi.org/10.1002/14651858.CD011114.pub2. Published 2017 Mar 16. Bei W, Wang Y, Chen J, et al. Chinese medicine FTZ recipe protects against highglucose-induced beta cell injury through alleviating oxidative stress. Evid Based Complement Alternat Med. 2019;2019:6378786. https://doi.org/ 10.1155/2019/6378786. Published 2019 Mar 3.

Chapter 6 Acute, chronic, recovery and prevention stages of PVD and DVT

Brostow DP, Hirsch AT, Pereira MA, Bliss RL, Kurzer MS. Nutritional status and body composition in patients with peripheral arterial disease: A crosssectional examination of disease severity and quality of life. Ecol Food Nutr. 2016;55(1):87e109. https://doi.org/10.1080/03670244.2015.1072817. Desai CK, Huang J, Lokhandwala A, Fernandez A, Riaz IB, Alpert JS. The role of vitamin supplementation in the prevention of cardiovascular disease events. Clin Cardiol. 2014;37(9):576e581. https://doi.org/10.1002/clc.22299. Han S, Chen Y, Wang J, et al. Anti-thrombosis effects and mechanisms by xueshuantong capsule under different flow conditions. Front Pharmacol. 2019;10:35. https://doi.org/10.3389/fphar.2019.00035. Published 2019 Feb 7. Hou YC, Lu CL, Zheng CM, et al. Emerging role of vitamins d and k in modulating uremic vascular calcification: the aspect of passive calcification [published correction appears in Nutrients. 2019 Mar 06;11(3):] Nutrients. 2019;11(1):152. https://doi.org/10.3390/nu11010152. Published 2019 Jan 12. Kim K, Park KI. A Review of antiplatelet activity of traditional medicinal herbs on integrative medicine studies. Evid Based Complement Alternat Med. 2019; 2019:7125162. https://doi.org/10.1155/2019/7125162. Published 2019 Jan 3. Kim K, Do HJ, Oh TW, et al. Antiplatelet and antithrombotic activity of a traditional medicine, Hwangryunhaedok-Tang. Front Pharmacol. 2019;9: 1502. https://doi.org/10.3389/fphar.2018.01502. Published 2019 Jan 9. Li H, Jiang Y, Wang Y, et al. The effects of warfarin on the pharmacokinetics of Senkyunolide I in a rat model of biliary drainage after administration of chuanxiong. Front Pharmacol. 2018;9:1461. https://doi.org/10.3389/ fphar.2018.01461. Published 2018 Dec 12. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8(8):CD006612. https://doi.org/10.1002/14651858.CD006612.pub5. Published 2017 Aug 17. Olas B. Dietary supplements with antiplatelet activity: a solution for everyone? Adv Nutr. 2018;9(1):51e57. https://doi.org/10.1093/advances/nmx014. Smolders VF, Zodda E, Quax PHA, et al. Metabolic alterations in cardiopulmonary vascular dysfunction. Front Mol Biosci. 2019;5:120. https:// doi.org/10.3389/fmolb.2018.00120. Published 2019 Jan 22. Steven S, Frenis K, Oelze M, et al. Vascular inflammation and oxidative stress: major triggers for cardiovascular disease. Oxid Med Cell Longev. 2019;2019: 7092151. https://doi.org/10.1155/2019/7092151. Published 2019 Jun 23. Teodoro JS, Nunes S, Rolo AP, Reis F, Palmeira CM. Therapeutic options targeting oxidative stress, mitochondrial dysfunction and inflammation to hinder the progression of vascular complications of diabetes. Front Physiol. 2019;9:1857. https://doi.org/10.3389/fphys.2018.01857. Published 2019 Jan 17. Touyz RM, Anagnostopoulou A, Camargo LL, Rios FJ, Montezano AC. Vascular biology of superoxide-generating nadph oxidase 5-implications in hypertension and cardiovascular disease. Antioxid Redox Signal. 2019;30(7): 1027e1040. https://doi.org/10.1089/ars.2018.7583.

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IV SECTION

Antibiotics

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7 Antibiotics Chapter Objectives 1. Introduce the purpose and use of antibiotic drugs. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of antibiotic drugs. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with antibiotic drugs. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.

Background Bacterial pericarditis, infective endocarditis, and myocarditis are common heart diseases directly caused by bacterial infections. The pericardium is the sac that surrounds and protects the heart. When it is affected by a bacteria or virus, inflammation and swelling can cause the heart to become restricted within the sac and seize pumping actions. Bacteria and viruses, which enter through the mouth, lungs, skin, intestines, and urinary tract, will travel in the blood stream and flow across the endocardium, the inner surface membrane of the heart and valves. The myocardium is the muscle of the heart; when a virus attacks the heart muscle, it causes tissue inflammation, which can affect the electrical impulses and impair heart pumping action. The infecting bacteria suspected of directly causing these heart diseases and others such as atherosclerosis, coronary artery disease, and events such as myocardial infarction include Staphylococcus aureus, Streptococcus pyogenes, and Chlamydia pneumoniae. The virus groups are adenovirus, Coxsackievirus B, Enteric cytopathic human orphan viruses, human parvovirus B19, and rubella.

Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00007-X Copyright © 2020 Elsevier Inc. All rights reserved.

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Origin Bacteria S. aureus This gram-positive bacterium commonly causes various skin infections including surgical infections. It can be difficult to treat because it forms a biofilm on surfaces. This biofilm makes antibiotics such as oxacillin, penicillin, and amoxicillin unable to penetrate to control or kill it; this phenomenon is called methicillin-resistant S. aureas (MERSA). MERSA is often picked up by immune-deficient or compromised patients at a hospital or skilled nursing setting when they have a surgical procedure (i.e., prosthetic orthopedic and heart valves, central venous catheters, urinary catheters, ear catheters, contact lenses, nasal implants) or have dialysis. S. pyogenes This Group A gram-positive bacterium commonly causes pharyngitis, pneumonia, toxic shock syndrome, strep throat, and various skin infections such as cellulitis, necrotizing faciitis, and impetigo. It can be difficult to treat because it forms a biofilm on surfaces. C. pneumoniae This bacterium is involved in respiratory tract infections, which is a common and recurring illness prevalent among individuals of all ages, especially children and elderly patients. Respiratory infections are mostly self-limiting, without serious symptoms, and usually treated or undertreated without medical attention; they can easily become a chronic condition. C. pneumoniae may be involved in the causes of the development of coronary heart disease (CHD). If a respiratory infection is rarely monitored and treated by most contracted individuals, this may account for widespread prevalence of CHD, which commonly leads to unstable angina/myocardial infarction.

Virus Adenovirus This virus commonly causes respiratory infections and urinary tract and gastrointestinal infections in patients of all ages. Infection can lead to heart problems. Cytomegalovirus This is a group of viruses that includes

Chapter 7 Antibiotics

• EpsteineBarr virus, which causes mononucleosis • Herpes simplex • Varicella-zoster, which causes chickenpox and later in life, shingles Coxsackievirus B This virus is transmitted by contact with fecal matter. It can cause flu-like symptoms such as fever, tiredness, and chest pain, which last up to 2 weeks. It is also part of the etiology of myocarditis, which can begin to develop around 2 weeks after the illness. Enteric cytopathic human orphan virus This virus is transmitted airborne or by contact with fecal matter. It includes a family of viruses that commonly affect the skin and gastrointestinal tract. When it infects the blood flow it is carried to the heart to cause myocarditis. Human parvovirus B19 This virus commonly causes fifth disease and is transmitted airborne. It is commonly diagnosed in children and institutionalized elderly patients. Rubella This virus commonly causes German measles in children and myocarditis later in life, similar to chickenpox, which causes shingles later in life and finally myocarditis. Vaccines are given in a series to newborns, infants, and children. Vaccines are currently a controversial subject in the parenting community, with many opting not to vaccinate children for various personal reasons.

Target Patients undergoing a long-term treatment course of antibiotic drugs in western medicine may be doing so for primary prevention of future ischemic heart conditions such as myocardial infarction and heart failure. Those physicians may prescribe and closely monitor cardiac patients on antibiotics such as tetracyclines or macrolides, though macrolide drugs may also carry a cardiovascular risk in some patients. Patients who seek assistance using traditional Chinese medicine are concerned about cardiovascular prevention. They may be aware of their past health condition results for the possibility of antibiotic drugs for pathogens that cause various infectious illnesses as well as cardiovascular diseases. Focus should be on balancing yin and yang, protecting

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flora of the gastro-intestinal tract, draining dampness that causes lipoprotein disorders, and tonifying qi and blood, which is pathogen dissipated toward anemia and immune depletion.

History and physical examination Bacterial pericarditis This disease is the infection, inflammation, and edema of the sac that surrounds the heart. Other bacteria that directly cause this condition include Streptococcus, Hemophilus influenza, and Meningococci. Infection signs and symptoms include: • Chills • Dry cough • Fever • Sweating Symptoms affecting the heart include: • Radiating chest pain • Breathing difficulty with pain increase on deep inspiration • Chest pain relief when standing or lying down • Fatigue

Infective endocarditis This disease is the infection of the inner lining of the heart and valves. This disease can be fatal if the patient does not seek prompt and effective treatment. Untreated/undertreated strep throat leads to rheumatic fever with the pathogen forming encrusting colonies on heart valves, breaking off to travel to other organs through the blood. Treatment involves being admitted into a hospital and administered intravenous antibiotics. Antibiotics are often administered in high doses and long term. Average treatment time is 4e6 weeks. Damaged heart valves may require surgery to be replaced. Infection signs and symptoms include: • Abnormal urine color • Chills • Fatigue • Muscle aches and pains • Night sweats Symptoms affecting the heart include: • Abdominal swelling • Bloody urine • Excessive sweating

Chapter 7 Antibiotics

• • • • • • • • • • • • • • • • • •

Janeway lesions Joint pain and swelling Leg and feet swelling Nail abnormalities Osler’s nodes Paleness Shortness of breath when active Weakness Weight changes Cardiovascular terminal complications include: Atrial fibrillation Brain abscess Congestive heart failure Emboli/thrombosis traveling to the lungs, heart, brain, or kidneys Glomerulonephritis Neurological and psycho-emotional changes Jaundice Stroke Valvular damage

Myocarditis This disease causes heart inflammation, which can lead to pericarditis, cardiomyopathy, and heart failure. Infection signs and symptoms may include: • Fever • Skin rash • Muscle aches • Headache • Diarrhea • Sore throat Symptoms affecting the heart include: • Abnormal heart rhythm • Fatigue and shortness of breath • Chest pain • Joint pain and lower limb swelling

Physical examination For patients with cardiovascular diseases associated with pathogenic infection, inspection should first include in order: • Cyanosis • Cachexia • Dyspnea

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• Edema • Jugular venous pressure (JVP) and other pulses for palpable sensations known as thrill turbulence • Checking blood pressure/heart rate/respiration and oximetry • Fingers for clubbing or splinter hemorrhages • Chest: breathing, contour changes, visible pulses, tympany, swelling, skin changes, and position of the apex as in cardiomegaly

Auscultation Heart sounds are the normal or pathological opening and closing of valves and the movement of blood through them. • Laminar flow is silent. • Turbulent flow makes a whooshing sound. • A thrill is palpable. Use the bell of the stethoscope: • for detecting lower-frequency sounds • to listen to the mitral valve Use the diaphragm of the stethoscope: • for higher frequencies • to listen to all areas of the chest

Levines scale of sound intensity I: Lowest intensity • Nearly impossible to hear II: Low intensity • Commonly heard by experienced listeners III: Medium intensity • Possible to be heard by anyone • No palpable thrill IV: Medium intensity • Possible to be heard by anyone • With palpable thrill V: Loud intensity • Possible to be heard by anyone with use of the diaphragm on the chest • With palpable thrill VI: Loudest intensity • Possible to be heard by anyone even with the diaphragm raised above the chest • With a palpable thrill

Chapter 7 Antibiotics

Patient positioning Auscultation can be performed with the patient sitting up, supine horizontal, reclined at a 45-degree angle, or decubitus (side lying). Aortic area • Patient should lie in the supine or sitting position. • Location in the right second intercostal space close to the sternum • Sound from the aortic valve can be heard by placing the diaphragm over the carotid artery to hear the carotid bifurcation. • Pathology: • Aortic murmur: common e Best heard using the diaphragm of the stethoscope e Common in elderly patients e Sign of advancing cardiovascular disease e Common in anemia e Common in feverish diseases e Common in thyrotoxicosis • Aortic regurgitation: common e Best heard with the patient in sitting position with stethoscope over the carotid artery e To hear the sound, have the patient lean forward, take a deep breath in, then out. This will allow a few seconds to listen for the regurgitation. • Aortic sclerosis: common in elderly patients e Sound may not transmit to the carotids e Sound may instead transmit to the apex and the midaxillary line e Sign of advancing cardiovascular disease • Aortic stenosis: common e Sound is transmitted to the carotids • Aortic aneurysm: common e Due to Marfan syndrome e Septal defect Erbs point • Patient should lie in the supine position. • Location in the left third intercostal space along the sternal border • Pathology: • Pericarditis: common e Heard at the left sternal edge e Crunching sound as the heart beats against inflamed and possibly stiffening sac

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Pulmonary area • Patient should be sitting up. • Location in the left second intercostal space close to the sternum • Best heard with the patient in sitting position with stethoscope over the carotid artery • To hear the sound, have the patient lean forward, take a deep breath in, then out. This will allow a few seconds to listen for the pulmonary pathology. • Pathology: • Pulmonary stenosis: common e Flow murmur sound creates a crescendoedecrescendo during systole (sound gets louder, then softer) e After sound becomes softer, it disappears on inspiration • Pulmonary regurgitation: common Tricuspid valve area • Patient should lie in the supine position. • Location in the inferior right sternal margin • Pathology: • Infective endocarditis: common e Murmur gets louder over time • Tricuspid murmurs: uncommon • Tricuspid stenosis: very rare • Tricuspid regurgitation: common e Does not radiate to the axilla e A wave sensation on jugular venous pressure palpation e Occurs in cardiomyopathy e Occurs in right ventricular hypertrophy Mitral valve area • Patient should lie in the left decubitus position so the heart hangs closer to the rib cage. • Located in the apical area along the lower right sternal edge • Pathology • Infective endocarditis: common e Murmur gets louder over time • Pan systolic murmur: sign of mitral valve regurgitation • Presystolic murmur: sign of mitral stenosis • Mid-systolic click: sign of mitral valve prolapse • Late diastolic murmur/Austin Flint: sign of mitral valve stenosis

Chapter 7 Antibiotics

• Myocarditis: common e Sound gets muffled over time e Third heart sound due to left ventricular failure e Mid-systolic click in mitral valve prolapse

Differential diagnosis See history and physical examination.

Clinical workup • • • • •

Blood tests: CBC, blood culture Echocardiography X-rays Stress test Nuclear heart scan testing

Treatment approaches Antibiotic prophylaxis This is recommended for patients with certain heart conditions or before undergoing a medical procedure. Other patients may be currently in treatment for an existing condition. Macrolides are a class of drugs commonly selected and include the azithromycin, clarithromycin, erythromycin, and quinolone. These drugs may impose an increased risk of ventricular tachyarrhythmia or sudden cardiac death in certain patients using herbal and nutritional substances. Three authoritative U.S. medical organizations with current opinions about prophylaxis include the American Heart Association (AHA), American Association of Orthopedic Surgeons (AOS) and American Dental Association (ADA). Despite differing opinions of both the AOS and ADA, the AHA has guidelines identifying specific types of cardiac patients who should take antibiotics prior to orthopedic or dental care, including those with • a heart transplant and artificial heart valves • a history of infective endocarditis • unrepaired or repaired congenital cardiovascular conditions • prosthetic material and devices placed during surgery or percutaneous intervention

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Traditional Chinese medicine

Traditional Chinese medicine formulas for arrhythmia. Herbal Medicine

Action

Wu wei xiao du yin Chuan xin lian Huang lian su wan Da huang mu pan pi tang Xi huang wan Zhi gan cao decoction Shen fu decoction Gui pi decoction

Clears viral toxic heat Clears toxic viral heat Clears toxic bacterial heat Clears and expels toxic heat drainage Clears heat, invigorates blood, protects the heart Recovers from illness, regulates heart functioning Recovers after an illness, warms yang Nourishes blood

Nutritional supplements Vitamin C Origin: Antioxidants from berries and citrus plants Benefits: Reduces inflammation and improves blood circulation Caution: Antioxidant use that may be prohibited in other health conditions

Vitamin D Origin: Seafood, egg yolk, mushrooms, cheese, beef liver, sun exposure Benefits: Immune functioning, bone and teeth health

Vitamin E Origin: Antioxidant found in meat, whole and oil variations of vegetables, fruits, and grains Benefits: Immune functioning, blood production, and selenium absorption Caution: May be contraindicated with anticoagulants, statins, niacin, and coumadins

Selenium Origin: Seafood, meat, egg yolk, beans, nuts, mushrooms

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Benefits: Immune functioning, biofilm penetration, and grampositive bacteria inhibition Caution: Interaction with aspirin, anticoagulants, clopidigrel, dalteparin, and lovenox

Pharmaceutical drugs Pharmaceutical drugs used in the treatment of pathogen-related cardiovascular complications include antibiotics, antiinflammatories, glucocorticosteroids, and digoxin.

Antibiotics

Prophylaxis

Treatment

Antiinflammatory

Positive inotropes

Amoxicillin Ampicillin

Penicillin G benzathine Penicillin G procaine Penicillin VK Allergic to penicillin Azithromycin Cephalexin Clarithromycin Clindamycin Erythromycin

Aspirin Glucocorticosteroids Prednisone

Digoxin

Further reading Meier CR. Antibiotics in the prevention and treatment of coronary heart disease. J Infect Dis. 2000;181(Suppl. 3):S558eS562. Int J Nanomed. 2011;6:1553e1558. https://doi.org/10.2147/IJN.S21729. Published online 2011 Jul 29. Tran PA, Webster TJ. Selenium nanoparticles inhibit Staphyococus aureus growth. J Trace Elem Med Biol. 2015;29:235e241. https://doi.org/10.1016/ j.jtemb.2014.07.020. Epub 2014 Aug 9. Baars EW, Zoen EB, Breitkreuz T, et al. The contribution of complementary and alternative medicine to reduce antibiotic use: a narrative review of health concepts, prevention, and treatment strategies. Evid Based Complement Alternat Med. 2019;2019:5365608. https://doi.org/10.1155/2019/5365608. Published 2019 Feb 3. Chassagne F, Huang X, Lyles JT, Quave CL. Validation of a 16th century traditional chinese medicine use of Ginkgo biloba as a topical antimicrobial. Front Microbiol. 2019;10:775. https://doi.org/10.3389/fmicb.2019.00775. Published 2019 Apr 16.

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Chevrette MG, Carlson CM, Ortega HE, et al. The antimicrobial potential of Streptomyces from insect microbiomes. Nat Commun. 2019;10(1):516. https://doi.org/10.1038/s41467-019-08438-0. Published 2019 Jan 31. He J, Li Z, Huang W, et al. Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial. BMJ Open. 2019;9(4):e024800. https://doi.org/10.1136/bmjopen-2018024800. Published 2019 Apr 2. Heise P, Liu Y, Degenkolb T, Vogel H, Schäberle TF, Vilcinskas A. Antibioticproducing beneficial bacteria in the gut of the burying beetle Nicrophorus vespilloides. Front Microbiol. 2019;10:1178. https://doi.org/10.3389/ fmicb.2019.01178. Published 2019 May 31. Lin PY, Chu CH, Chang FY, Huang YW, Tsai HJ, Yao TC. Trends and prescription patterns of traditional Chinese medicine use among subjects with allergic diseases: A nationwide population-based study. World Allergy Organ J. 2019; 12(2):100001. https://doi.org/10.1016/j.waojou.2018.11.001. Published 2019 Jan 26. Wang J, Wang L, Lou GH, et al. Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Pharm Biol. 2019;57(1):193e225. https://doi.org/10.1080/ 13880209.2019.1577466. Wu C, Wu HT, Wang Q, et al. Anticandidal potential of stem bark extract from schima Schima superba and the identification of its major anticandidal compound. Molecules. 2019;24(8):1587. https://doi.org/10.3390/ molecules24081587. Published 2019 Apr 22. Xia R, Hu X, Willcox M, et al. How far do we still need to go? A survey on knowledge, attitudes, practice related to antimicrobial stewardship regulations among Chinese doctors in 2012 and 2016. BMJ Open. 2019;9(6): e027687. https://doi.org/10.1136/bmjopen-2018-027687. Published 2019 Jun 5. Xu Z, Li H, Qin X, et al. Antibacterial evaluation of plants extracts against ampicillin-resistant Escherichia coli (E. coli) by microcalorimetry and principal component analysis. AMB Express. 2019;9(1):101. https://doi.org/ 10.1186/s13568-019-0829-y. Published 2019 Jul 11. Zhou JX, Braun MS, Wetterauer P, Wetterauer B, Wink M. Antioxidant, cytotoxic, and antimicrobial activities of Glycyrrhiza glabra L., Paeonia lactiflora Pall., and Eriobotrya japonica (Thunb.) Lindl. Extracts. Medicines (Basel). 2019;6(2): 43. https://doi.org/10.3390/medicines6020043. Published 2019 Mar 30.

V SECTION

Anti-atherosclerotics

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8 Atherosclerosis: The acute, chronic, recovery and prevention stages Chapter Objectives 1. Introduce atherosclerosis as a disease seen in integrative cardiovascular Chinese medicine. 2. Understand the history and physical examination procedures for monitoring atherosclerosis. 3. Introduce the methods of differential diagnoses. 4. Introduce treatment approaches according to Western medicine. 5. Introduce traditional Chinese medicine formulas for atherosclerosis. 6. Introduce nutritional supplements for atherosclerosis. 7. Introduce pharmaceutical drugs for atherosclerosis. 8. Discuss a perspective for treating patients with traditional Chinese herbal medicine, nutritional supplements, and/or pharmaceutical drugs in the acute and chronic stages. 9. Discuss a perspective for treating patients with traditional Chinese herbal medicine, nutritional supplements, and/or pharmaceutical drugs in the recovery and prevention stages.

Background Atherosclerosis is the diseased condition of the arteries around the heart and in the peripheral body. Atheroma is a soft substance made up of cholesterol and other substances found in the blood. It builds on the artery walls over decades, eventually reducing or blocking the flow of oxygenated blood. Hardened atheromas are often called plaque. Due to blood flow turbulence and other factors, the plaque can break. Breakage of the plaque can spill the soft sticky center content into the artery, causing cell fragments and platelets to stick to the content and form clots. Rapid buildup blocks blood flow, causing occlusion of the artery. Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00008-1 Copyright © 2020 Elsevier Inc. All rights reserved.

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• • • • • • •

•

• •

Composition of plaque: Cholesterol Atheromas Triglycerides Calcium Elastin White blood cells Main areas of blockage within the body: Coronary arteries: • Supply blood to the heart • Complete blockage causes myocardial infarction/heart attack • Aorta • Left coronary artery - Left descending artery - Circumflex artery • Right coronary artery - Right posterior descending artery - Descending artery - Acute marginal artery Carotid artery: • Supply blood to the head • Complete blockage causes ischemic or hemorrhagic stroke • Internal carotid artery - Scalp - Face - Neck • External carotid artery - Brain Renal artery: • Hypertension, increased urine protein, decreased kidney function, and foot and ankle edema Peripheral arteries: • Blockage causes numbness and pain • Arms - Brachial artery - Radial artery - Ulnar artery - Palmar arch • Legs - Iliac arteries - Femoral arteries - Popliteal arteries - Tibial arteries - Dorsalis pedis arteries

Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages

Patients who are not recommended or are not indicated for statin drugs will visit the traditional Chinese medicine (TCM) physician for cholesterol-lowering remedies. Obvious treatment principles are to balance yin and yang, clear heat, transform turbidity, expel toxins, dispel phlegm, and invigorate blood.

History and physical examination Patients will most likely have a history of:

Lipid levels • High LDL cholesterol and low HDL cholesterol • High triglycerides • Bacteroides: Gram-negative rod bacteria found in the gastrointestinal biome, soil, and seawater

Blood pressure • Sustained 140/90 mmHg and climbing higher • 130/80 mmHg or higher with diabetes

Inflammation • • • •

High C-reactive protein result Injury to arteries walls High blood sugar levels: diabetes and insulin resistance Insulin resistance

Genetics • Familial hypercholesterolemia types I, II, III, and IV History of stroke or myocardial infarction or presymptoms warning of future event: • Tight chest, neck, jaw, left arm, or shoulder blade area of the back • Severe fatigue • Severe headache • Clammy skin or cold sweat • Nausea or vomiting • Inability to breathe • Numbness or inability to move the face, arm, or leg on one side of the body • Trouble speaking • Trouble seeing • Dizziness and loss of balance leading to falling • Loss of consciousness

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Physical examination with confirming evidence: • Patient reports brain fog and forgetfulness when answering questions • Potential for hyperthyroid on palpation • Possible xanthomas around the eyes • Rapid weight gain and palpation of fatty areas around the waist and hips • Numbness and tingling of the arms, hands, legs, and feet • Blood pressure sustaining at 140/90 or above consistently over several office visits • Positive stress test and nuclear stress test results

Differential diagnosis Lab test

Detection

C-reactive protein Triglycerides Cardiac stress testing

Detects inflammation, a strong predictor of cardiovascular disease High levels suggest probability of atheromas forming in the arteries Performing exercise while connected to EKG to detect QRSPR changes that indicate reduction in oxygenation to the heart Sending a tube catheter through the femoral artery or radial artery to the main arteries of the heart to help detect blockages on X-ray

Angiogram/percutaneous intervention

Treatment approaches In both TCM and western medicine, the treatment goals for atherosclerosis include: • Relieving symptoms associated with clogged arteries • Assisting patients with lifestyle changes to reduce or eliminate risk factors and improve life quality • Reducing the risk and creation of atheromas, blood clots, and buildup of plaque • Monitoring symptoms of bacterial- and viral-causing illnesses • Preventing diseases associated with atherosclerosis • Widening or bypassing diseased arteries Treatments for atherosclerosis include herbal medicines and/ or pharmaceutical drugs, medical procedures, or surgery.

Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages

Coronary artery bypass grafting CABG is a surgical procedure for helping a patient improve chances of survival. It is a last resort effort used for end-stage diseased coronary arteries or arteries of the legs. The diseased arteries are not removed. Healthy arteries or veins are selected and harvested from other areas of the body and attached at safe distances around the diseased and narrowed arteries so that blood can bypass it and flow.

Traditional Chinese medicine

Traditional Chinese medicine formulas for arrhythmia Herbal medicine Yue jian cao you jiao wan Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling Xi huang wan Zhi gan cao decoction Shen fu decoction Gui pi decoction

Action Invigorates blood, dispels phlegm Invigorates blood, dispels phlegm Clears toxic bacterial and viral heat Clears toxic bacterial and viral heat Clears heat, invigorates blood, protects the heart Recovers from illness, regulates heart functioning Recovers after an illness, warms yang Nourishes blood

Nutritional supplements Alpha lipoic acid Nutritional constituents: Lipoic acid Benefits: Targets nerve cells, kidney, liver, lowers blood pressure, prevents cell damage to improve insulin use Caution: May lower blood sugar too much; avoid in pregnancy and nursing

Cod liver oil Nutritional constituents: Vitamins A, D, and omega-3 fatty acids (fish oils, flax seed, primrose, borage, and flaxseed oils) Benefits: Reduces cardiometabolic risk factors, protects sudden cardiac death after myocardial infarction, reduces raised

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plasma triglycerides, reduces blood pressure, and ameliorates atherogenic effects Caution: High doses required for reduction of blood pressure may have side effects.

Coenzyme Q-10 Nutritional constituents: CoQ10 Benefits: Heart, muscle, liver, and lungs; improves glycemic index, myocardial energy Caution: Body stores reduced when glyburide is prescribed for diabetes

Chromium Nutritional constituents: Picolinate, chloride, and nicotinate Benefits: pancreatic functioning and blood sugar Caution: May lower blood sugar excessively, causing concerns with medication indications

Magnesium Nutritional constituents: Citrate, stearate, and sulfate forms Benefits: Heart, kidneys, and muscle; improves type 2 insulin utilization in elderly Caution: May induce excessive stool elimination and diarrhea in patients at risk of inflammatory bowel disorders

Niacin Nutritional constituents: Vitamin B3 Benefits: Reduction of overall cholesterol levels, lowers triglycerides, increases HDL Caution: May cause nausea, may increase blood sugar levels, and may cause a prickly, flushing sensation on the skin

Potassium Nutritional constituents: Citrate Benefits: Cell membranes, reduces blood pressure Caution: May cause sodium retention and increased blood pressure

Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages

Selenium Nutritional constituents: Chelate Benefits: Small intestine and kidneys; helps protect nerves and vessels from excessive sugar intake damage Caution: Low levels may predispose to cancer, diabetes, and coronary artery disease

Vitamin B6 and Folic acid Nutritional constituents: Pyridoxine and folate Benefits: Liver, jejunum, ileum, and kidney; combined with B12 helps prevent stroke and loss of limbs and vision due to diabetes Caution: Excessive use of B6 may cause disfiguring skin lesions or folic acid nerve damage.

Vanadium Nutritional constituents: Sulfates and chelates Benefits: Liver and muscle cells to utilize insulin Caution: Nausea and cramping leading to diarrhea

Zinc Nutritional constituents: Picolinate Benefits: Production, storage, and secretion of insulin; blood sugar diffuse into cells Caution: May cause headache, nausea, vomiting, and drowsiness

Pharmaceutical drugs Atherosclerosis Ezetimibe: This drug reduces absorption of cholesterol in the small intestines and reduces LDL levels.

Bile acid sequestrants These drugs bind to bile acids in the small intestines to lower the acid, because it requires cholesterol to create it.

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Prescription plant sterols These drugs are called proprotein convertase substilisin kexin type 9 inhibitors and contain omega 3s. They are used by patients who need to lower triglyceride and cholesterol levels to reduce stroke and myocardial infarction risk but cannot take statin drugs.

Reduce blood clots Antiplatelets and aspirin are blood thinners, which prevent blood from forming atheromas and other clots. Clopidogrel is used to prevent clots from forming inside of artery stents. Ticagrelor and prasugrel are drugs used to prevent clots from forming inside of artery stents. They can be taken with aspirin.

Statins These drugs lower LDL and triglyceride levels and raise HDL levels. They decrease inflammation and help reduce the size of plaque. However, they may cause liver and kidney failure and muscle disorders.

Fibrates These drugs lower LDL and triglyceride levels and raise HDL levels.

Drugs to reduce high blood pressure Adrenergic agent This drug is for mild hypertension and is often used with other antihypertensive drugs for more severe hypertension.

Aldosterone antagonists These selective drugs compete with aldosterone receptor sites, reducing blood pressure and sodium reabsorption.

Alpha blockers These drugs selectively block postsynaptic alpha1 -adrenergic receptors and lower blood pressure by dilating arterioles and veins. Side effects include dizziness, headache, and drowsiness, in addition to orthostatic and first-dose hypotension.

Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages

Angiotensin converting enzyme Inhibitors These drugs are used in patients with hypertension, chronic kidney disease, and proteinuria. They suppress the reninangiotensin-aldosterone system by preventing the conversion of angiotensin I to angiotensin II and blocking the major pathway of the degradation of bradykinin by inhibiting angiotensinconverting enzymes (ACEs). They are often considered strong when used alone without a diuretic but can be combined with one.

Angiotensin Receptor blockers These drugs are primarily used when a patient is unable to tolerate ACE inhibitors. They block the binding of angiotensin II to angiotensin type I receptors, reduce effects of angiotensin IIeinduced vasoconstriction, reduce sodium retention, and reduce aldosterone release. Angiotensin receptor blockers are used alone or often combined with a diuretic.

Beta blockers See Chapter 11.

Calcium channel blockers These drugs are either dihydropyridines or nondihydropyridines. Some bind to L-type calcium channels, causing vasodilatation and a decrease in blood pressure. Others bind to L-type calcium channels in the sinoatrial and atrioventricular node. These drugs are often suggested for American patients of distant African ancestry and the elderly.

Acute and chronic stages Patients at risk for life-threatening symptoms associated with atherosclerosis should be treated only with western medicine methods and approaches. One main reason is for diagnostic and follow-up monitoring of sudden death. Another reason is because patients indicated for blood thinners have an increased risk of bleeding and must use caution in diet and lifestyle, and many herbal formulations will enhance the effects of the drug to dangerous levels. For many patients, medication and lifestyle changes can reduce the health risk and may help them become indicated for the benefits of nutritional supplements and herbal medicines in the future.

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Recovery and prevention stages Patients who are at a lower risk due to lipid imbalances and obesity, yet are not indicated for drug therapy, and those not indicated for statin therapy may benefit from natural medicine for prevention. Patients who become stabilized after treatment using western medicine methods and approaches may be indicated for natural medicine in the recovery stages. These patients may also notice immune benefits of natural remedies for bacterial and viral infections and herbal medicines that help build energy and well-being after illness. Laboratory studies would continue to monitor progress, especially for patients still at risk of adverse health chances due to heart or vessel injuries during the chronic stages.

Further reading Bi Y, Chen J, Hu F, Liu J, Li M, Zhao L. M2 macrophages as a potential target for antiatherosclerosis treatment. Neural Plast. 2019;2019:6724903. https:// doi.org/10.1155/2019/6724903. Published 2019 Feb 21. Ehrlich KC, Lacey M, Ehrlich M. Tissue-specific epigenetics of atherosclerosisrelated ANGPT and ANGPTL genes. Epigenomics. 2019;11(2):169e186. https://doi.org/10.2217/epi-2018-0150. Han J, Wang Y, Yuan Z, et al. Nonalcoholic fatty liver disease represents a greater metabolic burden in patients with atherosclerosis: A cross-sectional study. Medicine (Baltimore). 2019;98(11):e14896. https://doi.org/10.1097/ MD.0000000000014896. Huang Y, Hu H, Liu L, et al. Interleukin-12p35 deficiency reverses the Th1/Th2 Imbalance, aggravates the Th17/Treg imbalance, and ameliorates atherosclerosis in ApoE-/- mice. Mediators Inflamm. 2019;2019:3152040. https://doi.org/10.1155/2019/3152040. Published 2019 Apr 10. Kim SM, Huh JW, Kim EY, et al. Endothelial dysfunction induces atherosclerosis: increased aggrecan expression promotes apoptosis in vascular smooth muscle cells. BMB Rep. 2019;52(2):145e150. https://doi.org/10.5483/ BMBRep.2019.52.2.282. Lietava J, Beerova N, Klymenko SV, Panghyova E, Varga I, Pechanova O. Effects of cornelian cherry on atherosclerosis and its risk factors. Oxid Med Cell Longev. 2019;2019:2515270. https://doi.org/10.1155/2019/2515270. Published 2019 Feb 17. Marchio P, Guerra-Ojeda S, Vila JM, Aldasoro M, Victor VM, Mauricio MD. Targeting early atherosclerosis: a focus on oxidative stress and inflammation. Oxid Med Cell Longev. 2019;2019:8563845. https://doi.org/10.1155/2019/ 8563845. Published 2019 Jul 1. Onat UI, Yildirim AD, Tufanli Ö, et al. Intercepting the lipid-induced integrated stress response reduces atherosclerosis. J Am Coll Cardiol. 2019;73(10): 1149e1169. https://doi.org/10.1016/j.jacc.2018.12.055. Summerhill VI, Grechko AV, Yet SF, Sobenin IA, Orekhov AN. The atherogenic role of circulating modified lipids in atherosclerosis. Int J Mol Sci. 2019; 20(14):3561. https://doi.org/10.3390/ijms20143561. Published 2019 Jul 20.

Chapter 8 Atherosclerosis: The acute, chronic, recovery and prevention stages

€ ller M, et al. G-protein coupled receptor van der Vorst EPC, Peters LJF, Mu targeting on myeloid cells in atherosclerosis. Front Pharmacol. 2019;10:531. https://doi.org/10.3389/fphar.2019.00531. Published 2019 May 22. Yang L, Gao C. MiR-590 inhibits endothelial cell apoptosis by inactivating the TLR4/NF-kB pathway in atherosclerosis. Yonsei Med J. 2019;60(3):298e307. https://doi.org/10.3349/ymj.2019.60.3.298. Yu H, Ma S, Sun L, Gao J, Zhao C. TGF-b1 upregulates the expression of lncRNAATB to promote atherosclerosis. Mol Med Rep. 2019;19(5):4222e4228. https://doi.org/10.3892/mmr.2019.10109. Zhou Z, Chen Y, Zhang D, et al. MicroRNA-30-3p suppresses inflammatory factor-induced endothelial cell injury by targeting TCF21. Mediators Inflamm. 2019;2019:1342190. https://doi.org/10.1155/2019/1342190. Published 2019 Jul 2. Zhu J, Nelson K, Toth J, Muscat JE. Nicotine dependence as an independent risk factor for atherosclerosis in the National Lung Screening Trial. BMC Public Health. 2019;19(1):103. https://doi.org/10.1186/s12889-019-6419-8. Published 2019 Jan 22.

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VI SECTION

Antiglycemics

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9 Acute, chronic, prevention, and recovery stages Chapter Objectives 1. Introduce diabetes types 1 and 2, the patient signs and symptoms, and the various health conditions that result from diabetes. 2. Discuss history and physical examination of patients with various types of diabetes. 3. List the values in clinical workup and treatment approaches. 4. Discuss the actions and benefits of formulas in traditional Chinese medicine, nutritional supplements, and pharmaceutical drugs. 5. Discuss the indications for isolated use or integration of herbs, nutritional supplements, and pharmaceutical drugs during the acute, chronic, recovery, and prevention stages.

Background Antiglycemic drugs are used to help insulin control blood glucose levels. Insulin is a hormone that gets glucose into cells to create energy. Insulin deficiency causes excess glucose in the blood. In type 1 diabetes the pancreas does not make enough insulin and in type 2 diabetes, insulin is not utilized properly in the body. Antiglycemic drugs are taken by patients with diabetes, however nephropathy, retinopathy, neuropathy, vascular diseases, and ketoacidosis are long-term complications due to diabetes. They will warrant the need to include other medications and approaches during treatment.

Diabetic nephropathy This is a chronic kidney and renal disease often resulting in the need for dialysis and kidney transplant. If either treatment fails, the patient will die.

Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00009-3 Copyright © 2020 Elsevier Inc. All rights reserved.

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Retinopathy This is a disease involving the damaged or blocked blood vessels in the retina of the eye that potentially lead to abnormal vessel growth, cataracts, and glaucoma. Severity stages include mild nonproliferative, moderate nonproliferative, severe nonproliferative, and proliferative.

Neuropathy This is a disease involving damage to peripheral nerves of the CNS, arms, hands, legs, and feet. It also damages the autonomic nervous system that controls automatic functions such as bladder functioning, blinking, blood vessel contraction and heartbeat, lungs, and intestinal peristalsis.

Vascular diseases Peripheral vascular disease is a disease factor of atherosclerosis and involves clot blockages in the limbs, both of which are advancing rapidly due to diabetes. The lower legs are primarily affected causing coldness, numbness, “pins-and-needles” tingling, cramping, and at times open sores. Cerebral vascular accident is an event caused by an acute episode involving blood supply to the brain. It may be another factor of atherosclerosis advancing rapidly due hypertension and complicated by diabetes affecting kidney functioning. There are three types: • Ischemic stroke: vessel obstruction blocking blood flow to the brain • Transient ischemic attack: temporary interruption of blood flow to a section of the brain • Hemorrhagic stroke: vessel rupture causing flooding of blood in the brain

Diabetic ketoacidosis This condition is characterized by a liver condition involving the production of high levels of ketones circulating in the blood, which are produced mainly because insulin is not present so cells are not receiving glucose, and fatty acids are instead being synthesized for energy. Other causes include bacterial and viral infections, pancreas injury, and fasting (in susceptible individuals). These loose ketones cause the pH of the blood to drop quickly, possibly resulting in sudden death.

Chapter 9 Acute, chronic, prevention, and recovery stages

The main reason patients seek traditional Chinese medicine is to help with the control of blood sugar, lipid levels, and to increase energy levels. Overall the treatment principles will possibly include nourishing kidney and liver yin, clearing deficiency heat, generating fluid, tonifying spleen, and replenishing jing.

History and physical examination History It is best to understand some history about possible genetic and environmental causes of type 1 and 2 diabetes to designate evaluation and methods for ongoing management. The genetic factors can involve mutations of cells that alter cell and immune response to insulin levels in the blood. The major histocompatibility complex (HLA) contains various gene serotypes and IDDM1 and IDDM2, DR3 and DR4 are of interest in diabetes. When mutations of IDDM1 and IDDM2 insulin production genes are circulated in the blood, they are usually noticed as an antigen. The Coxsackie virus is an environmental factor that causes autoimmune responses, especially concerning the pancreas’s ability to produce insulin. Individuals with an HLA variation including DR3 and DR4 and have the Coxsackie virus will create antibodies that destroy the beta cells in the pancreas that produce insulin. Symptoms of gestational and prediabetes associated only with type 2: • Acanthosis nigricans • Fatigue and exhaustion • Dizziness and fainting • Sleep problems • Gastrointestinal problems • HDL levels below 40 mg/dL or triglyceride levels of more than 150 mg/dL • Hypertension 140/90 or higher • Polycystic ovary syndrome • Thirst and dry mouth • Altered sensations in the extremities • Frequent and profuse urination • Muscle and joint pain and stiffness • Rapid and considerable weight gain over short period of time (up to 100 lb or 45 kg within 1 year)

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Symptoms of kidney disease Patients may not realize kidney disease is present until it has advanced to dangerous stages of nephropathy. Symptoms include: • High levels of protein detected in the urine • Easy bruising • Blood urea nitrogen markers are high • Localized edema seen on the face, hands, and feet but not in the chest and abdomen

Symptoms of diabetic ketoacidosis • • • • • • • • • • • • • • • •

Abdominal paindin about 30% of patients Vomiting or nausea Stomach pain Polyphagiadincreased appetite or constant hunger Headache Flushed face Kussmaul’s respiration Dry skin Dry mouth with polydipsia Dehydration Breath that is fruity smelling Shortness of breath and breathing difficulty when lying down History of fainting or loss of consciousness Fatigue Stiff muscles Polyuria

Symptoms of neuropathy • Pins-and-needles sensation on the feet and lower legs that come and go even if legs are set for maximum circulation • Piercing, stabbing, or burning sensations in one area of the foot or hand • Sensitive to sensations and fabric textures • Feeling of skin crawling or something crawling on the skin

Symptoms of hypoglycemia Initial symptoms • • • •

Light-headed feeling with body tremors Cold perspiration Nausea yet hungry Rapid heartbeat

Chapter 9 Acute, chronic, prevention, and recovery stages

More serious symptoms with evidence that the central nervous system may be affected • • • • • • • • •

Body weakness Anxiety Slurred speech with difficulty communicating Delayed reflex actions Dizziness and confusion Headache Sleepiness Seizures or convulsions Unconsciousness or coma

Physical exam and management • Lab tests: Glucose and lipids • Eyes: Signs of retinopathy • NeckdSpecific focus on the glands: enlargement of thyroid gland, abnormalities in the lymph nodes • Auscultation of heart and lungs, bruit of the pulses • Electrocardiogram • Blood pressure • Palpation: Sensitivities of the liver, stomach, and intestines and pulses that may indicate an abdominal aneurysm • Arms: Muscle sensitivity • Legs: Muscle sensitivity, edema, knee and ankle reflexes, foot deformity, peripheral neuropathy, bruised skin or ulcers, and numbness and tingling

Clinical workup Glycated hemoglobin test (A1c): • Average blood sugar levels in the body over the last 2e 3 months by measuring the blood sugar attached to the blood hemoglobin • Normal: ¼ /6.5% • Fasting blood glucose and impaired fasting glucose: • Done after fasting for at least 8 hours • Normal: 35 in with close monitoring especially during perimenopausal stage and after menopause • HDL cholesterol levels decreased, often lower than LDL levels: • Men 7 mm revealed during a revascularization procedure is a predictor of future unstable angina, myocardial infarction necessitating revascularizations, and sudden death

Recovery and prevention stages Recovery Clinical management of angina due to problems with poor microvascular circulation in Syndrome X often includes lifestyle modification practices. • Changing food and beverage items to those that are conducive to meeting therapeutic goals • Adopting an exercise practice that helps to strengthen heart muscles and promote blood flow • Balancing blood lipid levels • Reducing body fat • Reducing and eliminating factors that lead to confirmed diabetes Patients taking nitrates often experience side effects that may linger or resolve after completing a medication course: Qi, blood, phlegm, and dampness issues: • Dizziness • Headache • Lightheadedness • Low blood pressure • Nausea • Skin flushing around the face and neck Symptoms to prompt emergency assistance: • Vision blurring • Trouble breathing • Swelling of the face and lips and inside of the mouth

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• Persistent headache • Skin rash including hives When weaning from nitrates to a modified lifestyle that may involve the use of other medications. When indicated, alternate Chinese medicine formula(s) that recover after illness with pharmaceutical drugs. Administer within 3 hours before or after pharmaceutical drug doses. Chinese medicine formulas: • Modified yue jian cao you jiao wan • Modified bao jian mei jian fei cha • Modified xi huang wan • Modified zhi gan cao decoction • Modified shen fu decoction • Modified gui pi decoction Continue a traditional Chinese medicine formula that recovers after illness and within 2 weeks after weaning from nitrates and pharmaceutical drugs, incorporate formula(s) that address rhythm activity, phlegm, and blood sugar: • Modified yu quan wan • Modified zuo gui wan • Modified liu wei di huang wan • Modified zhi gan cao decoction Continue a traditional Chinese medicine formula that recovers after illness while monitoring vitals such as blood sugar, cholesterol, blood pressure, and so forth. At optimal results in clinical examination, incorporate formula(s) that address blood nourishment, opening of channels, and calming shen: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin

Prevention Lifestyle factors to consider: • Abstain from smoking cigarettes and tobacco use • Limit the amount of any kind or form of sugar in daily and weekly meal planning • Check hormonal levels regularly and adjust needs according to milestones at middle age such as menopause and andropause • Check CBC at regular levels, especially for early detection of anemia and lipid levels • Check blood sugar daily • Check blood pressure daily

Chapter 14 Nitrates

• Suggest a dietary plan that is conducive to maintaining control of health and well-being • Use proper measures to completely recover from infections and get tested within suggested timeframes after courses of medicines to be sure Formulas to consider: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin • Modified liu wei di huang wan

Further reading Al-Mohammad A. Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction. ESC Heart Fail. 2019;6(4):878e883. https://doi.org/ 10.1002/ehf2.12459. Battas A, Gaidoumi AE, Ksakas A, Kherbeche A. Adsorption study for the removal of nitrate from water using local clay. ScientificWorldJournal. 2019;2019: 9529618. https://doi.org/10.1155/2019/9529618. Published 2019 Feb 3. Górski J, Dragon K, Kaczmarek PMJ. Nitrate pollution in the Warta river (Poland) between 1958 and 2016: trends and causes. Environ Sci Pollut Res Int. 2019; 26(3):2038e2046. https://doi.org/10.1007/s11356-017-9798-3. Lu L, Rao X, Cong R, et al. Design, synthesis and biological evaluation of nitrate derivatives of sauropunol a A and b B as potent vasodilatory agents. Molecules. 2019;24(3):583. https://doi.org/10.3390/molecules24030583. Published 2019 Feb 6. Smith K, Muggeridge DJ, Easton C, Ross MD. An acute dose of inorganic dietary nitrate does not improve high-intensity, intermittent exercise performance in temperate or hot and humid conditions. Eur J Appl Physiol. 2019;119(3): 723e733. https://doi.org/10.1007/s00421-018-04063-9. Tatarczak-Michalewska M, Flieger J, Kawka J, et al. HPLC-DAD determination of nitrite and nitrate in human saliva utilizing a phosphatidylcholine column. Molecules. 2019;24(9):1754. https://doi.org/10.3390/molecules24091754. Published 2019 May 6. Zhang M, Shi JC, Wu LS. Factors influencing the accuracy of the denitrifier method for determining the oxygen isotopic composition of nitrate. J Zhejiang Univ Sci B. 2019;20(1):49e58. https://doi.org/10.1631/ jzus.B1800197.

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XII SECTION

Lipid modifiers

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15 Lipid modifiers Chapter Objectives 1. Introduce the purpose and use of lipid-modifying drugs. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of lipid-modifying drugs. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with lipid-modifying drugs. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.

Background See Chapter 8 regarding atherosclerosis. Statins are a class of drugs used in primary prevention and for treatment of excess cholesterol levels and to balance LDL and HDL. Excess cholesterol in the blood and sometimes calcium builds up into a hard, waxy substance on vessel and artery walls. The hard, waxy substance is called plaque. Blood cells and other fatty material and microbes in the blood also collect on the plaque to form clots. More plaque will then build to cover the clots. The clots act as soft centers, which make the plaque weak and brittle. When the plaque breaks the soft blood clots and infection can flow out and block the artery at some distance. If this does not happen, the stiff plaque can build up enough to completely block blood flow. Both possibilities commonly cause myocardial infarction or stroke. The action of statin drugs is to reduce or stop the production of cholesterol by suppressing HMG-CoA, the liver enzyme that is responsible. The purpose is to lower LDL and triglyceride levels, provide opportunity to raise HDL levels, and reduce or eliminate Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine https://doi.org/10.1016/B978-0-12-817580-4.00015-9 Copyright © 2020 Elsevier Inc. All rights reserved.

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chances of infarction by 40% and heart disease related deaths by 30%. Statin drugs present a hopeful clinical result. However, there are populations of people who may not benefit because of improper prescribing, noncompliance, and side effects. Patients who are neither recommended nor indicated for statin drugs often look to natural therapies. Many visit the traditional Chinese medicine (TCM) physician for cholesterol-lowering remedies. Considering a full workup including syndrome differentiation and important preexisting western medicine diagnoses, treatment principles are to balance yin and yang, clear heat, transform turbidity, expel toxins, dispel phlegm, invigorate blood, and break blood stasis.

History and physical examination See Chapter 8 regarding atherosclerosis.

Differential diagnosis See Chapter 8 regarding atherosclerosis.

Clinical workup See Chapter 8 regarding atherosclerosis.

Treatment approaches See Chapter 8 regarding atherosclerosis.

Guidelines See Chapter 8 regarding atherosclerosis.

Traditional Chinese medicine See Chapter 8 regarding atherosclerosis.

Nutritional supplements Cod liver Oil Nutritional constituents: Vitamins A, D, and omega-3 fatty acids (fish oils, flax seed, primrose, borage, and flaxseed oils)

Chapter 15 Lipid modifiers

Benefits: Reduces cardiometabolic risk factors, protects sudden cardiac death after myocardial infarction, reduces raised plasma triglycerides, reduces blood pressure, and ameliorates atherogenic effects Caution: High doses required for reduction of blood pressure may have side effects

Niacin Nutritional constituents: Vitamin B3 Benefits: Reduction of overall cholesterol levels, lowers triglycerides, increases HDL Caution: May cause or exacerbate liver disease symptoms, irritate gastric ulcers, lower blood pressure too much

Pharmaceutical drugs Lipid-lowering agents Statins: HMG-CoA reductase inhibitors These drugs inhibit HMG-CoA reductase to eliminate cholesterol production. Apolipoprotein B antisense oligonucleotide These agents affect VLDL to lower LDL and total cholesterol levels by targeting apolipoprotein B (apoB).

Bile acid sequestrants These drugs sequester the bile duct to lower cholesterol and LDL.

Fibrates These drugs decrease hepatic production of cholesterol and absorption in the gastrointestinal tract.

MTP inhibitor These drugs bind to microsomal triglyceride transfer protein to reduce and prevent ApoB-containing lipoproteins such as LDL and cholesterol.

Acute and chronic stages See Chapter 8 regarding atherosclerosis.

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Acute stage Some patients are prescribed statin drugs based on borderline results during a workup and risk factors such as age and weight. They may not have vascular disease, but they do have high cholesterol levels. They may be on statins as a prophylaxis to guard against high chances of developing heart disease. The course may be temporary until a modified lifestyle can be established that shows. Supplementing with omega 3, niacin, and extra vitamin B3 may provide favorable results in some patients. Chinese herbal formulas may be included after weaning off of statin drugs to continue cholesterol-reducing effects until proper dietary choices can suffice.

Traditional Chinese formulas • Modified yue jian cao you jiao wan • Modified bao jian mei jian fei cha

Chronic stage Some patients are prescribed statin drugs based on results during routine diagnostic tests. They have vascular disease and high cholesterol levels, both of which are risk factors for atherosclerosis, myocardial infarction, stroke, and heart disease. They may be on a combination of statins and other cardiovascular drugs to reduce cholesterol levels and chances of mortality. Combination drugs for cholesterol reduction and blood pressure control: • Atorvastatin and amlodipine • Atorvastatin and ezetimibe • Lovastatin and niacin (nicotinic acid) • Simvastatin and ezetimibe • Simvastatin and niacin These patients commonly experience side effects of statin use that include: Shen and blood deficiency disturbances: • Difficulty sleeping with drowsiness during active periods, active during sleep periods • Headache • Dizziness • Memory loss • Mental confusion Musculoskeletal side effects: • Elevated creatinine kinase, which causes muscle inflammation

Chapter 15 Lipid modifiers

• • • •

Muscle and joint aches Muscle tenderness to the touch Myalgia: weakness with inability to exercise Myositis: inflammation, especially with statin and fibrates together • Peripheral neuropathy • Rhabdomyolysis: overall body muscle pain with severe inflammation that releases protein into the blood stream causing kidney failure and sudden death Gastrointestinal side effects: • Nausea • Vomiting • Blood sugar elevation to the point of developing confirmed type 2 diabetes • Abdominal cramping • Bloating due to fluid or gas • Diarrhea • Constipation Dermatological side effects: • Skin rash • Skin flushing Physicians will discontinue statins due to complications from drug interaction, side effects, and little to no benefit over an expected period of long-term use. Some patients who seek TCM care may need constitutional rescue during the feathering component of weaning stage, before planning and managing treatment. • Modified zhi gan cao decoction • Modified shen fu decoction • Modified gui pi decoction

Recovery and prevention stages See Chapter 8 regarding atherosclerosis. Yue jian cao you jiao wan Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling Xi huang wan

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Further reading Banerjee S, Kundu A. Lipid-drug conjugates: a potential nanocarrier system for oral drug delivery applications. Daru. 2018;26(1):65e75. https://doi.org/ 10.1007/s40199-018-0209-1. Corradi V, Sejdiu BI, Mesa-Galloso H, et al. Emerging diversity in lipid-protein interactions. Chem Rev. 2019;119(9):5775e5848. https://doi.org/10.1021/ acs.chemrev.8b00451.  M, Huynh K, et al. Exceptional human longevity is associated with Pradas I, Jove a specific plasma phenotype of ether lipids. Redox Biol. 2019;21:101127. https://doi.org/10.1016/j.redox.2019.101127. Solati Z, Ravandi A. Lipidomics of bioactive lipids in acute coronary syndromes. Int J Mol Sci. 2019;20(5):1051. https://doi.org/10.3390/ijms20051051. Published 2019 Feb 28. Xie T, Gorenjak V, G Stathopoulou M, et al. Epigenome-wide association study (EWAS) of blood lipids in healthy population from STANISLAS family study (SFS). Int J Mol Sci. 2019;20(5):1014. https://doi.org/10.3390/ijms20051014. Published 2019 Feb 26. Yang H, Young D, Gao J, et al. Are blood lipids associated with microvascular complications among type 2 diabetes mellitus patients? A cross-sectional study in Shanghai, China. Lipids Health Dis. 2019;18(1):18. https://doi.org/ 10.1186/s12944-019-0970-2. Published 2019 Jan 18.

XIII SECTION

Positive inotropes

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16 Inotropic Drugs Chapter Objectives 1. Understand to use of inotropic drugs for patients with hypertension, angina, arrhythmia, cardiomyopathy, and myocardial infarction and during a cardiac procedure. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of inotropic drugs. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with inotropic drugs. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.

Background See Chapters 5, 6, 8, 10, and 11. Generally, inotropic drugs are medicines used for symptoms of heart failure including hypertension, angina, arrhythmia, and cardiomyopathy, and after a myocardial infarction or a cardiac surgical procedure. The heart potentially suffers due to decreasing blood pressure and rhythmic disturbance affecting the contraction of the heart muscle and producing poor cardiac output. Oxygen deprivation and lactic acid formation leads to organ failure and death. Following a cardiac event or procedure, hemodynamic studies are performed monitoring: • Arterial pressure • Cardiac output • Central venous pressure Inotropes are identified as positive or negative and are introduced to change the force of heart muscle contractions. • Positive inotropes • Heart failure • Cardiomyopathy Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00016-0 Copyright © 2020 Elsevier Inc. All rights reserved.

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• Myocardial infarction • Cardiogenic shock • Bind to potassium and sodium receptors to control and stop calcium from leaving myocardial cells • Strengthen the contractions with fewer heart beats to pump more blood • Negative inotropes • Hypertension • Arrhythmia • Angina • Weaken the contractions and slow down the heart rate • Reduces stress on the heart following myocardial infarction to prevent future events Positive inotropes are most commonly prescribed because they help meet the oxygen needs of the heart and the rest of the body tissues. Digoxin is one of the medicines prescribed to elderly patients to set arterial pressure, cardiac output, and central venous pressure at a predicted range to maintain life. The reasons some patients may seek traditional Chinese medicine (TCM) care is to address chief complaints of low energy and lethargy or some side effects of medication. Such patients should be screened and worked up using western medicine methods anyway, as well as Chinese medicine methods. The reason is to rule out an impending emergency, any diagnosed or undiagnosed health condition that affects the thyroid, liver, or kidney function and any known cardiovascular history with past or present reasons to contraindicate Chinese medicine. If it is elected to involve the use of herbal medicine treatment, it would be wise to perform a hemodynamic analysis and examination. Upon confirmation that high output and pressure levels may endanger the patient and introducing herbal formulas that have the action of positive inotropic drugs that will have a therapeutic benefit, choose the formulas and modify them wisely with regular hemostatic monitoring. Without a careful analysis, understanding of cardiac physiology, diseases, and the western medicine therapeutic principle in such cases, a TCM physician may make a fatal mistake. The fatal mistake would be believing that the patient needs to tonify qi and yang; then induce herbal treatment to stimulate energy, thus producing a noticeable result in the short term. Realize that a patient with a known history and background of managed care for heart failure and myocardial infarction may less likely be cleared by a liable managing medical doctor and more likely voluntarily switching care plans in noncompliance. If it is indicated to adopt or incorporate a natural healthcare regimen at the time of visit, consider that herbs in properly

Chapter 16 Inotropic Drugs

designed formulas may act as positive inotropes, function to increase the heart rate, and may be used clinically to treat congestive heart failure patients. Herbs in properly designed formulas may act as negative inotropes, which function to decrease the strength of muscular contractions, and may be used clinically to treat high blood pressure. In western medicine, it is commonly indicated that the physician would elect to put the patient on positive inotrope drugs upon encounter in emergency hospital care and during routine outpatient management. Many patients, especially those with a pacemaker, will likely be on a regimen that includes inotropes including digoxin. Should a TCM physician accept the patient for treatment, it would be wise to exclude herbal formulas or herbs in a modified formula that will contradict the predicted treatment principle ordinarily set for such cases in western medicine in the future. When deciding to prescribe modified formulas, watch for selection, dosing, and substituting or using cardiotonic herbs with glycosides as one of the constituents.

History See Chapters 5, 6, 8, 10, and 11.

Differential diagnosis See Chapters 5, 6, 8, 10, and 11.

Clinical workup See Chapters 5, 6, 8, 10, and 11.

Treatment approaches See Chapters 5, 6, 8, 10, and 11.

Traditional Chinese medicine See Chapters 5, 6, 8, 10, and 11.

Nutritional supplements See Chapters 5, 6, 8, 10, and 11.

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Pharmaceutical drugs See Chapters 5, 6, 8, 10, and 11.

Acute and chronic stages See Chapters 5, 6, 8, 10, and 11.

Acute stage Inotropes are often introduced during a major cardiac event or to control heart functioning to maintain life during end stages of heart failure. Nutritional supplements and herbal formulas should be withdrawn at this time.

Chronic stage Patients are dealing with tachycardia and the more advanced cases are always in danger of possible sudden death from arrhythmia and myocardial ischemia due to oxygen consumption. In addition, they are also dealing with medication side effects: Cardiovascular • Arrhythmia • Dizziness and fainting • Dyspnea • Hypotension • Palpitations • Sweating Endocrine/hormonal disturbances • Erectile dysfunction • Decreased sex drive • Gynecomastia Gastrointestinal disturbances • Diarrhea • Loss of appetite • Nausea • Vomiting Neurological disturbances • Dizziness or lightheadedness • Headache Vision disturbances • Blurred vision • Color halos: white, green, or yellow

Chapter 16 Inotropic Drugs

• Double vision • Light sensitivity Patients in this stage will become inotropic dependent because weaning efforts often result in kidney dysfunction and gradually sustaining hypotension at dangerous lows. Symptoms of heart failure will get worse, prompting increased frequency of emergency room visits, major life-saving mid- and end-stage organ surgical procedures, and hospital inpatient stays. Inotropic therapy will be used in hospitalized patients: • Those who have shown evidence of end-stage organ hypoperfusion • Those who may need support until research or specialist decisions are made, otherwise known as a bridge to decision • Those who have been elected to undergo serious surgical intervention necessary to sustain life: • Mechanical circulatory support • Heart transplant Poor candidates for herbal and drug inotropic therapy: • For those patients who are not candidates for advanced heart replacement therapy, intravenous inotropes may also be considered as palliation at the end of life. • Patients who are experiencing angina or rhythm disturbances that do not respond to drug therapy because of heart failure and ischemic cardiomyopathy • The same patient with heart failure and ischemic cardiomyopathy without current symptoms, but who would experience adverse effects of drugs that increase oxygen demand • Patients who are better candidates for outpatient coronary revascularization • Patients who would be candidates of mechanical cardiovascular devices that would provide a better therapeutic outcome than medications

Recovery and prevention stages Recovery stage Some patients who are under the care of western medicine physicians may be cleared to introduce natural aspects to treatment with extreme caution and monitoring such as CoQ10, potassium, and Chinese herbal medicine formulas. These choices should coincide with and be subjective to needs seen in clinical management. Caution with modifying formulas with herbs such as

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Kushen, milk weed, lily of the valley, and hawthorn; mao di huang, shu di huang, and sheng di huang; and other cardiotonic herbs with glycosides as part of plant or natural substance constituents.

Prevention stage See Chapters 5, 6, 8, 10, and 11.

Further reading Askari A. The sodium pump and digitalis drugs: dogmas and fallacies. Pharmacol Res Perspect. 2019;7(4):e00505. https://doi.org/10.1002/prp2.505. Published 2019 Jul 19. Guth BD, Engwall M, Eldridge S, et al. Considerations for an in vitro, cell-based testing platform for detection of adverse drug-induced inotropic effects in early drug development. Part 1: general considerations for development of novel testing platforms. Front Pharmacol. 2019;10:884. https://doi.org/ 10.3389/fphar.2019.00884. Published 2019 Aug 9. Koponen T, Karttunen J, Musialowicz T, Pietiläinen L, Uusaro A, Lahtinen P. Vasoactive-inotropic score and the prediction of morbidity and mortality after cardiac surgery. Br J Anaesth. 2019;122(4):428e436. https://doi.org/ 10.1016/j.bja.2018.12.019. Neumann J, Hofmann B, Gergs U. On inotropic effects of UTP in the human heart. Heliyon. 2019;5(8):e02197. https://doi.org/10.1016/j.heliyon.2019.e02197. Published 2019 Aug 2. Schumann J, Henrich EC, Strobl H, et al. Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev. 2018;1(1):CD009669. https://doi.org/ 10.1002/14651858.CD009669.pub3. Published 2018 Jan 29.

XIV SECTION

Vasodilators

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17 Vasodilators Chapter Objectives 1. Understand the use of vasodilators for patients with hypertension and heart failure. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of vasodilators. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with vasodilators. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.

Background See Chapters 4 and 10.

History See Chapters 4 and 10.

Differential diagnosis See Chapters 4 and 10.

Clinical workup See Chapters 4 and 10.

Treatment approaches See Chapters 4 and 10.

Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00017-2 Copyright © 2020 Elsevier Inc. All rights reserved.

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Traditional Chinese medicine See Chapters 4 and 10.

Nutritional supplements See Chapters 4 and 10.

Pharmaceutical drugs See Chapters 4 and 10.

Acute and chronic stages See Chapters 4 and 10.

Recovery and prevention stages See Chapters 4 and 10.

Further reading Dong Y, Chen H, Gao J, Liu Y, Li J, Wang J. Bioactive ingredients in chinese herbal medicines that target non-coding RNAs: promising new choices for disease treatment. Front Pharmacol. 2019;10:515. https://doi.org/10.3389/ fphar.2019.00515. Published 2019 May 21. Guo F, Zhang W, Su J, Xu H, Yang H. Prediction of drug positioning for quan-duzhong capsules against hypertensive nephropathy based on the robustness of disease network. Front Pharmacol. 2019;10:49. https://doi.org/10.3389/ fphar.2019.00049. Published 2019 Feb 12. zquez FJ, Romo-Mancillas A, RojasMedina-Ruiz D, Erreguin-Luna B, Luna-Va Molina A, Ibarra-Alvarado C. Vasodilation elicited by isoxsuprine, identified by high-throughput virtual screening of compound libraries, involves activation of the NO/cGMP and H₂S/KATP pathways and blockade of a₁adrenoceptors and calcium channels. Molecules. 2019;24(5):987. DOI:10.3390. Published 2019 Mar 11. Nilsson KF, Gustafsson LE. Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism. Pharmacol Res Perspect. 2019;7(1):e00462. https://doi.org/10.1002/prp2.462. Published 2019 Jan 22. Paladugu N, Shaqra H, Blum S, Bhalodkar NC. Positive vasodilator stress ECG with normal myocardial perfusion imaging and its correlation with coronary angiographic findings in African Americans and Hispanics. Clin Cardiol. 2010;33(10):638e642. https://doi.org/10.1002/clc.20783.

Chapter 17 Vasodilators

Shah RM, Singh M, Bhuriya R, Molnar J, Arora RR, Khosla S. Favorable effects of vasodilators on left ventricular remodeling in asymptomatic patients with chronic moderate-severe aortic regurgitation and normal ejection fraction: a meta-analysis of clinical trials. Clin Cardiol. 2012;35(10):619e625. https:// doi.org/10.1002/clc.22019. Shi R, Wang Y, An X, et al. Efficacy of co-administration of liuwei dihuang pills and ginkgo biloba tablets on albuminuria in type 2 diabetes: a 24-month, multicenter, double-blind, placebo-controlled, randomized clinical trial. Front Endocrinol (Lausanne). 2019;10:100. https://doi.org/10.3389/ fendo.2019.00100. Published 2019 Feb 22.

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Index ‘Note: Page numbers followed “t” indicates tables.’ Abnormal ejection fraction, 139 A1c test, 124 Active pharmaceutical ingredient, 29e30 Acute stage, 48e49, 86, 113, 128e129, 168, 190, 198e199 to chronic stages acute and chronic stages, 152e153 history and physical examination, 58e65 nutritional supplements, 152 pharmaceutical drugs, 152 traditional Chinese medicine (TCM), 57e58, 151, 151t Adenosine, 59e60, 71 Adenovirus, 92 Adrenergic agent, 46, 112 Aldosterone antagonists, 46, 112 Alpha/beta-adrenergic agonists, 71 Alpha-blockers, 46, 112 Alpha-glucosidase inhibitors, 127 Alpha lipoic acid, 44, 109, 125 Ambulatory blood pressure monitoring, 40 Amiodarone, 60, 70 Anginal chest pain, 174 Angiotensin-converting enzyme inhibitors, 46, 113, 143 Angiotensin-2 receptor antagonists, 143e144 Angiotensin receptor blockers, 47, 113, 143e144 Antibiotic prophylaxis, 99

Antibiotics, 101, 101t Anticoagulants, 84e85 Anticonvulsants, 71 Antidysrhythmic drugs, 67 Antithrombotic drugs, 80 Atherosclerosis, 111 Auscultation, 96 Bacteria, 92 Bacterial pericarditis, 94 Baseline laboratory evaluation, 40 Ben Cao Bei Yao, 6 Berberine, 125 Beta 1/Beta 2 Adrenergic agonists, 71 Beta-blockers, 47, 60e61, 113 Bile acid sequestrants, 111, 189 Bioflavonoids, 83 Blood pressure, 107 JNC 7 classification of, 36t Blood tests, 139e140 BNP, 139e140 Brain zaps, 72 Calcium channel blockers (CCBs), 47, 61, 113, 157e159, 158t Calcium chloride, 66 California proposition 65, 22 Cardiovascular disease, 137, 137t Central-acting alpha 2-agonists, 47 Chloride blood test, 140 Cholesterol level targets, 41e42 Chromium, 45, 110, 125 Chronic stage, 48e49, 86, 113, 128e129, 135e137, 144, 168, 190e191, 198e199

acute stage to acute and chronic stages, 152e153 history and physical examination, 58e65 nutritional supplements, 152 pharmaceutical drugs, 152 traditional Chinese medicine (TCM), 57e58, 151, 151t areas of heart failure and symptoms, 136 classification, 136 clinical workup, 139e140 differential diagnosis, 139 history and physical examination, 137e138 nutritional supplements, 142e143 objective assessment of cardiovascular disease, 137, 137t pharmaceutical drugs, 143e144 symptoms during activity, 136, 136t traditional Chinese medicine, 142 treatment approaches, 140e141 Class IA antidysrhythmics, 68e69 Class IB antidysrhythmics, 69 Class IC antidysrhythmics, 69e70 Class III antidysrhythmics, 70 Class V antidysrhythmics, 71 Cod liver oil, 44, 65, 109e110, 142, 188

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Index

Coenzyme Q-10, 45, 66, 110, 142 Common antiarrhythmic agents, 59e65 Constitutional theories, 8, 8te15t Coronary artery bypass grafting, 109 Coxsackievirus B, 93 C. pneumoniae, 92 Cytomegalovirus, 92e93 D-dimers testing, 82 Decoction dosage, 16t Deep vein thrombosis (DVT), 79 Diabetic ketoacidosis, 120e121 symptoms of, 122 Diabetic nephropathy, 119 Diazepam, 71 Differential diagnosis, 39e40, 65, 82, 108, 176 Digestive enzymes, 83e84 Dipeptidyl peptidase-4 inhibitors, 127 Disopyramide, 61, 68 Diuretics, 47, 166e167 Dronedarone, 61, 70 Drugs to reduce high blood pressure, 112e113 Echocardiography, 41 Ejection fraction, 139 Electrocardiography, physical examination with, 59 Enteric cytopathic human orphan virus, 93 Essential fatty acids, 84 Federal Food and Drugs Act of 1906, 19 Federal Food, Drug and Cosmetic Act, 19e20 Federal Meat Inspection Act of 1906, 19 Fibrates, 112, 189 Flecainide, 62, 69e70 Folic acid, 46, 111

“Generally regarded as safe” (GRAS), 20 Genetics, 107e108 Genome-wide association studies, 37 Glucose output and uptake reducers, 127e128 Glycated hemoglobin, 124 Heart failure, 174 Herbal formulas 1e3, 74 Huangdi Nei Jing, 1e2 Hua Yang Zang Xiang Yue Zuan, 6 Human CD34 + stem cell therapy, 177e178 Human parvovirus B19, 93 Hypertension screening tests, 39t Hypertension treatment based on U.S. racial profiles, 43t Hypertensive emergencies, 38e39 Hypoglycemia, symptoms of, 122e123 Infective endocarditis, 94e95, 98 Inflammation, 107 Insulin output increasers, 127 Insulin resistance reducers, 128 Islamic medicine, 27e28 Isoproterenol, 71 Kidney disease, symptoms of, 122 L-carnitine, 66, 142e143 Lidocaine, 62e63, 69 Lifestyle modifications, 41 Lipid levels, 107 Lipid-lowering agents, 189 Loop diuretics, 47, 166e167 Lorazepam, 71 Low molecular weight heparins, 85 Lumbrokinase, 84

Magnesium, 45, 110, 125e126, 166 Magnesium sulfate, 67, 143 Melatonin, 126 Methicillin-resistant S. aureas (MERSA), 92 Mexiletine, 62e63, 69 Midazolam, 71 Ming dynasty, 5 Mitral valve area, 98e99 Modern pharmacology, recorded transition toward, 27 Monoamine oxidase inhibitors (MAOIs), 72 MTP inhibitor, 189 Myocarditis, 95, 99 Nattokinase, 84 Negative inotropes, 196 Nei Ke Zhai Yao, 5 Neuropathy, 120 symptoms of, 122 Niacin, 110, 143, 188 Noninsulin injected drugs, 128 Nonsteroidal antiinflammatory drugs, 37 Nonsulfonylurea group, 127 Norepinephrine, 71 Normal ejection fraction, 139 NT-proBNP, 139e140 Nutritional supplements, 44e46, 83e84, 100e101, 109e111, 125e126, 152, 188, 197 calcium chloride, 66 California proposition 65, 22 cod liver oil, 65 coenzyme Q10, 66 early government regulations, 19e21 L-carnitine, 66 magnesium, 166 magnesium sulfate, 67 N-acetyl cysteine, 179 potassium, 165e166 regulation in United States, 19 regulations for future practices, 21e22

Index

sodium bicarbonate, 67 vitamin C, 166, 178e179 Nutrition Labeling and Education Act (NLEA), 21 Omega-3 fatty acids, 126 Oracle bones of Taoists, 1 Oral and injectable insulin drugs, 127 Oral glucose tolerance test, 124 Organ system dysfunction, due to hypertension, 36t Patient positioning, 97e99 Peripheral vascular disease (PVD), 79 Pharmaceutical drugs, 25, 46e48, 84e85, 101, 111e113, 127e128, 143e144, 152, 166e167, 189, 198 acute and chronic stages, 159e160 calcium channel blockers (CCBs), 157e159, 158t cardiac action potentials, 67e71 chronic stages, 180e181 nitrates, 179e180, 179t recovery and prevention stages, 160e161 therapy, 177 Pharmacological therapy, 43e44, 180e181 Physical exam and management, 123 Plasma glucose tolerance test, 124 Positive inotropes, 195e196 Potassium, 45, 110, 165e166 Potassium sparing, 47, 167 Prescription plant sterols, 112 Preserved ejection fraction (HFpEF), 139 Prevention stages, 49e50, 86, 114, 129e130, 168, 181e183, 200

Primary hyperaldosteronism, 37 Probiotics, 126 Procainamide, 63, 68e69 Propafenone, 63e64, 70 Pu Ji Fang, 5 Qin and Han dynasties, 2e3 Qing dynasty, 5e6 Quinidine, 64, 69 Recorded transition, toward modern pharmacology, 27 Recovery stage, 49e50, 86, 114, 129e130, 168, 181e183, 199e200 Recovery suggestion, 13te15t Reduce blood clots, 112 Reduced ejection fraction (HFrEF), 139 Renin inhibitors, 48 Retinopathy, 120 Rubella, 93 Safe Drinking Water and Toxic Enforcement Act of 1986, 22 S. aureus, 92 Screening tests, 41 Secondary hypertension, 37 Selective serotonin reuptake inhibitors (SSRIs), 72 Selenium, 45, 100e101, 111 Shanghan Za Bing Lun, 2 Shen Nong Ben Cao Jing, 2 Shi Bing Lun, 6 Sodium bicarbonate, 67 Song dynasty, 4 Sotalol, 64e65, 70 Sound intensity, levines scale of, 96 S. pyogenes, 92 Statin drugs, 188 Statins, 112, 187 Sui dynasty, 3e4 Sulfonylurea group, 127 Syndrome X, 173e174

209

Systemic lupus erythematosus (SLE) syndrome, 63 Target-organ disease, 40 Therapeutic index, 29 Thiazides, 47, 167 Thrombolytics, 85 Traditional Chinese formulas, 190 Traditional Chinese medicine (TCM), 1e7, 57e58, 65, 83, 100, 100t, 109, 125, 142, 151, 151t, 188, 196e197 common herbs used in Chinese medicine cardiology, 17, 17te18t formulas for hypertension, 43t herbal preparation and delivery types, 15e16, 16t Ming dynasty, 5 Qin and Han dynasties, 2e3 Qing dynasty, 5e6 Song dynasty, 4 Sui dynasty, 3e4 twentieth century China, 6e7 twenty-first century China, 7 Treatment approaches, 108e109 Tricuspid valve area, 98 Twentieth century China, 6e7 Twenty-first century China, 7 Urine Ketones, 124 U.S. racial profiles, hypertension treatment based on, 43t U.S. Recommended Daily Allowance (RDA), 20e21 Vanadium, 46, 111, 126 Vascular diseases, 120 VaughneWilliams classes, 67 Virus, 92e93 Vitamin B-1, 126 Vitamin B6, 46, 111 Vitamin C, 100, 166 Vitamin D, 100, 126 Vitamin E, 100 Vitamin K antagonists, 85

210

Index

Western medicine pharmacology, 26 Western medicine treatment, 83 Xue Zheng Lun, 6

Yao Xing Ben Cao, 4 Yellow Emperor, 1 Yi Fang Kao, 5 Yi Gaun, 6 Yin Dynasty, 1

Zhong Xi Hui Tong Yi Jing Jing Yi, 6 Zhonxi Hui Tong Yi Shu Wu Zhong, 6 Zinc, 46, 111 Zu Sheng Bai Jian, 5