Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine [2, 1 ed.] 0128175745, 9780128175743

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Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine [2, 1 ed.]
 0128175745, 9780128175743

Table of contents :
Cover
Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine: Integrative Cardiovascular Chinese Medicine Series Volume 2
Copyright
Dedication
In Memory
Preface
The Development, Promotion, and Ongoing Research of Integrative Cardiovascular Chinese Medicine
Dr. Al-Shura biography
Other Titles by Dr. Anika Niambi Al-Shura
Part I: Medical empathy in prescribing, modifying and weaning
1 . Establishing a therapeutic rationale during treatment
Acute stage
Chronic Stage
Recovery Stage
Prevention Stage
Further Reading
2 . Partnering with compliant patients
Medical empathy
Patient compliance
Physician/patient relationship
Further reading:
Part II: Basic overview of pharmacologic systems
3 . Discussion of drug classes and types
Class IA antiarrhythmics
Class IB antidysrhythmics
Class IC antidysrhythmics
Class III antidysrhythmics
Class V antidysrhythmics
Inotropics
Alpha/beta-adrenergic agonists
Beta 1/beta 2 adrenergic agonists
Anticonvulsants
Anticoagulants
Antiplatelets
Antiglycerides
Antihypertensives
Antiglycemics
Injected drugs
Diuretics
Nitrates
Further Reading
4 . Traditional Chinese medicine
A brief history of medicine, pharmacology, and formula preparation in traditional Chinese medicine
During the Qin and Han Dynasties (221 BC–AD 220)
Sui Dynasty (AD 581–618) and Tang Dynasty (AD 618–907)
Song Dynasty (AD 960–1108)
Ming Dynasty (AD 1368–1644)
Qing Dynasty (AD 1644–911)
20th century China (AD 1912–1999)
21st century China
Constitutional theories
Using traditional Chinese medicines: herbal preparation and delivery types
Most common herbs used in Chinese medicine cardiology
Antihypertensive formulas
Antiarrhythmic formulas
Antithrombotic formulas
Antibiotic formulas
Antilipid formulas
Antiglycemic formulas
ACE inhibitor formulas
Diuretic formulas
Further Reading
5 . Nutritional supplements
History of nutritional supplement regulation in the United States
Early government regulations
Regulation for future practices
California proposition 65
Antihypertensive nutrients
Alpha lipoic acid
Cod liver oil
Coenzyme Q-10
Chromium
Magnesium
Potassium
Chromium
Selenium
Vitamin B6 and folic acid
Vanadium
Zinc
Antiarrhythmic nutrients
Cod liver oil
Coenzyme Q10
L-carnitine
Calcium chloride
Magnesium sulfate
Sodium bicarbonate
Antithrombotic nutrients
Bioflavonoids
Digestive enzymes
Essential fatty acids
Nattokinase
Lumbrokinase
Antibiotic nutrients
Vitamin C
Vitamin D
Vitamin E
Selenium
Antilipidemic nutrients
Alpha lipoic acid
Cod liver oil
Coenzyme Q-10
Chromium
Magnesium
Niacin
Potassium
Selenium
Vitamin B6 and folic acid
Vanadium
Zinc
Alpha-lipoic acid
Berberine
Chromium
Magnesium
Melatonin
Omega-3 fatty acids
Probiotics
Vanadium
Vitamin B-1
Vitamin D
Angiotensin-converting enzyme inhibitor nutrients
Cod liver oil
Coenzyme Q-10
L-carnitine
Magnesium sulfate
Niacin
Diuretic nutrients
Potassium
Magnesium
Vitamin C
Further Reading
6 . Pharmaceutical drugs
Ancient influence on western medicine pharmacology
Recorded transition toward modern pharmacology
Islamic medicine
Modern history
Therapeutic index
Narrow index
Wide index
Active pharmaceutical ingredient
Further Reading
Part III: Treatment principles & strategies
7 . Treating according to disease stages
Acute stage
Blood pressure
Arrhythmia
Acute stage
Nutrients: One or all
Antithrombotics
Atherosclerotics
Antiglycemics
Hypertension/beta blockers
Nutrients: One or all
Hypertension/calcium channel blockers
Nutrients: One or all
Diuretics
Lipidemia/statins
Traditional Chinese formulas
Positive inotropes
Chronic stage
Blood pressure
Arrhythmia
Common symptoms associated with taking common antiarrhythmic agents
Adenosine
Amiodarone
Beta blockers
Calcium channel blockers
Dronedarone
Disopyramide
Flecainide
Lidocaine and mexiletine
Procainamide
Propafenone
Quinidine
Sotalol
Antithrombotics
Atherosclerotics
Antiglycemics
Hypertension
Hypertension/beta blockers
Hypertension/calcium channel blocker
Diuretics
Lipidemia/statin
Lipidemia/statins
Positive inotropes
Recovery stage
Blood pressure
Antithrombotics
Atherosclerotics
Antiglycemics
Hypertension/calcium channel blockers
Diuretics
Recovery stage
Symptoms that require emergency assistance
Heart failure nitrates
Pharmacological therapy
Nitrates
Recovery
Positive inotropes
Prevention stage
Blood pressure
Antithrombotics
Atherosclerotics
Hypertension/calcium channel blockers
Diuretics
Nitrates
Lipidemia/statins
Further Reading
8 . Lipoprotein, hypertension, and diabetes
Lipoprotein disorders
Current medications
Traditional Chinese medicine
Nutritional supplements
Alpha lipoic acid
Cod liver oil
Coenzyme Q-10
Chromium
Magnesium
Niacin
Potassium
Selenium
Vitamin B6 and folic acid
Vanadium
Zinc
Pharmaceutical drugs
Bile acid sequestrants
Prescription plant sterols
Statins
Fibrates
Drugs to reduce high blood pressure
Adrenergic agent
Aldosterone antagonists
Alpha blockers
Angiotensin-converting enzyme inhibitors
Angiotensin receptor blockers
Beta blockers
Beta-1 receptor blockers
Calcium channel blockers
Acute and chronic stages
Recovery and prevention stages
Hypertension
Primary hypertension: environmental and genetic causes
Secondary hypertension: renal system failures
JNC 7 classification and recommendations to lower blood pressure
Management
Current medications
Traditional Chinese medicine
Nutritional supplements
Alpha lipoic acid
Cod liver oil
Coenzyme Q-10
Chromium
Magnesium
Potassium
Chromium
Selenium
Vitamin B6 and folic acid
Vanadium
Zinc
Pharmaceutical drugs
Adrenergic agent
Aldosterone antagonists
Alpha blockers
Angiotensin converting enzyme inhibitors
Angiotensin receptor blockers
Beta blockers
Beta-1 receptor blockers
Calcium channel blockers
Central-acting alpha 2-agonists
Diuretics
Loop diuretics
Potassium sparing
Thiazides
Renin inhibitors
Acute and chronic stages
Acute stage
Chronic stage
Recovery and prevention stages
Herbal formulas: 1–3
Clinical pearls
Diabetes
Prediabetes
Type 2 diabetes and dawn phenomenon
Management
Glucose studies
HbA1c
Current medications
Traditional Chinese medicine
Nutritional supplements
Alpha lipoic acid
Berberine
Chromium
Magnesium
Melatonin
Omega-3 fatty acids
Probiotics
Vanadium
Vitamin B-1
Vitamin D
Pharmaceutical drugs
Oral and injectable insulin drugs
Insulin output increasers
Sulfonylurea group
Alpha-glucosidase inhibitors
Glucose output and uptake reducers
Insulin resistance reducers
Noninsulin injected drugs
Acute and chronic stages
Recovery and prevention stages
Further Reading
9 . Cardiac rhythm diseases
Background on heart blocks
Atrioventricular block
Ventricular arrhythmias
Arrhythmogenic right ventricular dysplasia/cardiomyopathy
Current medications/treatment
AV block
Traditional Chinese medicine
Nutritional supplements
Cod liver oil
L-carnitine
Calcium chloride
Magnesium sulfate
Sodium bicarbonate
Pharmaceutical drugs
Class IA antidysrhythmics
Disopyramide
Procainamide
Quinidine
Class IB antidysrhythmics
Lidocaine
Mexiletine
Class IC antidysrhythmics
Flecainide
Propafenone
Class III antidysrhythmics
Amiodarone
Dronedarone
Sotalol
Class V antidysrhythmics
Adenosine
Alpha/beta-adrenergic agonists
Norepinephrine
Beta 1/beta 2 adrenergic agonists
Isoproterenol
Anticonvulsants
Diazepam
Lorazepam
Midazolam
Acute and chronic stages
Acute stage
Chronic stage
Further Reading
10 . Chamber and valve diseases
Atrioventricular block
Ventricular arrhythmias
Arrhythmogenic right ventricular dysplasia/cardiomyopathy
Valvular heart disease
Mitral valve prolapse
Bicuspid aortic valve
Current medications
Traditional Chinese medicine
Nutritional supplements
Pharmaceutical drugs
Acute and chronic stages
Further Reading
11 . Vascular diseases
Background
Peripheral vascular disease and deep vein thrombosis
Stroke
Current medications
Peripheral vascular disease
Stroke
Traditional Chinese medicine
Nutritional supplements
Bioflavonoids
Digestive enzymes
Essential fatty acids
Nattokinase
Lumbrokinase
Pharmaceutical drugs
Anticoagulants
Low molecular weight heparins
Vitamin K antagonists
Thrombolytics
Acute and chronic stages
Recovery and prevention stages
Further Reading
Index

Citation preview

Integrative Cardiovascular Chinese Medicine Series

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine Volume 2

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: 978-0-12-817574-3 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

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.

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.

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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Preface

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

Preface

xiii

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

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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Dr. Al-Shura biography

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 Establishing a therapeutic rationale during treatment Chapter Objectives 1. Introduce common cardiovascular disease conditions in integrative cardiovascular Chinese medicine through the acute, chronic, recovery, and prevention stages of cardiovascular disease conditions. 2. Introduce the purpose of treatment. 3. Indicate whether herbal formulas could be the only treatment. 4. Indicate whether the integration of herbs, nutrition, and pharmaceutical drugs could be used in treatment. 5. Indicate whether pharmaceutical drugs are the only preferred method of treatment.

This chapter discusses the health factors and the purpose and possible effectiveness of isolated and integrative treatment through each stage.

Acute stage

Condition

Purpose of treatment

Hypertension

Stabilizing the patient back to normal blood pressure levels or regular life from a painful event or condition that raised the blood pressure

Herbal formula treatment only

Integrative herbs and drugs

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00001-1 Copyright © 2020 Elsevier Inc. All rights reserved.

Pharmaceutical drugs only

3

4

Chapter 1 Establishing a therapeutic rationale during treatment

dcontinued

Condition

Purpose of treatment

Arrhythmia

Reversing arrhythmia symptoms during or after a temporary non-life-threatening illness

Hyperlipidemia Stimulating the body's natural ability to digest fats; utilization and distribution of fats for normal body functions that require fats Breaking up the clotted blood or Peripheral removal or foreign obstruction vascular within the affected vessel disease Atherosclerosis Vessel and endothelial protection, control or elimination of vessel inflammation, control or elimination of the fatty streak of the lipid layer Prophylaxis due to borderline diagnosis due to very high cholesterol levels plus age and weight with other steadily developing cardiovascular symptoms Diabetes Control of temporary blood sugar elevation or drop that has caused reversible adverse symptoms, stimulating the body's natural ability to metabolize sugars for normal body functions that require sugars Diuretics Patient experiences a stressor or the effects of an illness that raises blood pressure, causes exhaustion or physical strain, breathing difficulty, and lower body edema

Herbal formula treatment only

Integrative herbs and drugs

Pharmaceutical drugs only

Chapter 1 Establishing a therapeutic rationale during treatment

Chronic Stage

Condition

Purpose of treatment

Hypertension

Stabilizing the uncontrolled stage 2 blood pressure levels when high blood pressure can affect the eyes, overall well-being, aldosterone production, and lifethreatening circulation to the brain and the kidneys. There can be suspected pheochromocytoma and bilateral renal artery stenosis or stenosis found in one or both kidneys. Patients at the chronic stage and taking nitrates for confirmed diagnoses will have a prior history of serious noncompliance. They may likely not be indicated for Chinese herbal medicine and nutritional supplements, especially vitamin C and cysteine. The effectiveness is still subjective to findings in lab studies, disease stage, body constitution, and overall prognosis. None will have satisfactory clinical effects of much significance over the long term because concentric remodeling in confirmed and advancing diseases states does not present reversal. Pharmacodynamics of nitrates can increase blood pressure and the likelihood of anginal chest pains and emergency events if

Herbal formula Treatment only

Integrative herbs and drugs

Pharmaceutical drugs only

5

6

Chapter 1 Establishing a therapeutic rationale during treatment

dcontinued

Condition

Arrhythmia

Hyperlipidemia

Peripheral vascular disease

Purpose of treatment interacted with other ingested pharmaceutical drugs or Chinese herbal medications. Men are especially affected as certain blood pressure medications, with side effects that enhance experiences during sexual encounters, can experience excessively dangerous drops in blood pressure, which can be fatal. Clinical management of advancing heart failure with coronary artery disease and metabolic syndrome as causative factors involves disease surveillance, balancing health factors within subjective yet acceptable ranges. Sustaining normal rhythm to prevent asystole and sudden death Patients 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 Prophylaxis against potential lifethreatening events. These types of patients may have a history

Herbal formula Treatment only

Integrative herbs and drugs

Pharmaceutical drugs only

Chapter 1 Establishing a therapeutic rationale during treatment

Atherosclerosis

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. Patients at risk of 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. Prophylaxis due to diagnosis of very high cholesterol levels plus age and weight, other steadily developing cardiovascular symptoms, positive stress test, and percutaneous intervention (PCI) result of 50% or more occlusion

7

8

Chapter 1 Establishing a therapeutic rationale during treatment

dcontinued

Condition

Purpose of treatment

Diabetes

Confirmed diabetes diagnosis, patients can present with at least two other common occurrences concerning glycemic levels. The first is diabetic dermopathy. This condition involves the skin, and complaints range from itchiness, flakiness, and acanthosis nigricans of the neck, back, arm pits, elbows, knuckles, and knees to hemorrhage and erosion ulcers that are often complicated by fungal and bacterial infections. The second is hypoglycemia. This happens in patients who are using injected or oral insulin and can occur in patients with diabetes for a variety of reasons including insulin resistance and lack of insulin production. Treatment strategy must include the type and stage of the diabetes and body constitution. Patients should understand proper timing, such as how to predict peak action of insulin when indicated snacks, meals, herbs, and nutritional supplements can be integrated with oral or injected pharmaceutical drugs. Patients with chronic and confirmed diabetes type 1 and 2 frequently

Herbal formula Treatment only

Integrative herbs and drugs

Pharmaceutical drugs only

Chapter 1 Establishing a therapeutic rationale during treatment

Diuretics

monitor for several complications including diabetic ketoacidosis (DKA). DKA is preventable but when it does occur symptoms are typically dehydration with elevated glucose levels. They are hospitalized to rehydrate, restore electrolytes, and bring elevated glucose levels under control and stabilized. For patients with uncontrollable diabetes, those who are noncompliant, with DKA or kidney disease, herbs and nutrients may mostly likely be prohibited due to monitoring of a restricted diet, and pharmaceutical drug therapy is required. Heart failure and or kidney failure impending or diagnosed, which compromises overall well-being or threatens life Some patients may need to live on a fluid restriction, including drinks and food, of a minimum of 1 L up to a maximum of 2 L daily. Some patients may need to live on a salt restriction to assist with the desire to drink more fluids.

9

10

Chapter 1 Establishing a therapeutic rationale during treatment

Recovery Stage

Condition Hypertension

Purpose of Treatment

Implementing a strategy 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 During the recovery stage, when a patient is weaning off of calcium channel blocker (CCB) drug therapy to herbal formulas for hypertension, patients often adopting a lifestyle that improves health. Food and nutritional choices in the diet must exclude pomelo and grapefruit whole or in juices. These products interfere with the pharmacodynamics of the medication, potentially causing harm due to accumulation of unmetabolized drug within the body. It is advised to give a time window of at least 4 h between consuming grapefruit and ingesting CCBs. Reducing diastolic blood pressure in increments of 2 mmHg to help decrease the risk of stroke by 15% and the risk of coronary heart disease by 6% Hyperlipidemia Patients 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. To help with male virility, leg swelling, back pain, and overall energy. Practitioners may

Herbal formula Integrative Treatment Herbs and Pharmaceutical Only Drugs Drugs Only

Chapter 1 Establishing a therapeutic rationale during treatment

find, among other therapeutic principles, that the traditional Chinese medicine differentiations of 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. Atherosclerosis Assisting 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 wellbeing 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. 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. Use caution with modifying formulas with herbs, kushen, milk weed, lily of the valley, hawthorn, mao di huang, shu di huang, sheng di huang, and other cardiotonic herbs with glycosides as part of plant or natural substance constituents. Peripheral vascular disease

11

12

Chapter 1 Establishing a therapeutic rationale during treatment

dcontinued

Condition

Diabetes

Purpose of Treatment Prophylaxis due to diagnosis of very high cholesterol levels plus age and weight, other steadily developing cardiovascular symptoms, positive stress test, and PCI result of 50% or less occlusion 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 h before or after pharmaceutical drug doses. To help the body utilize and regulate normal use of glucose in the blood, normal lipid accumulation and metabolism, and sufficient blood content and levels. Single or simple herb combinations and nutritional supplementation can be used in daily health tonics, short-term regimens, and culinary use to enhance dietary practices. Understanding of the body constitution and proper timing is important. Patients must be educated on how to predict peak action of insulin and other symptoms and be guided about how to create a lifestyle to remain literate and proactive. Monitored through tapering down of prescribed pharmaceutical drugs. It is important to educate them about properly utilizing food and medicine. They should be educated about snacks and meals, and when and how to integrate single or simple herb combinations and nutritional supplements with oral or injected pharmaceutical drugs. Continue a TCM formula that recovers after illness and within 2 weeks after weaning

Herbal formula Integrative Treatment Herbs and Pharmaceutical Only Drugs Drugs Only

Chapter 1 Establishing a therapeutic rationale during treatment

Diuretics

13

from nitrates and pharmaceutical drugs; and incorporate formula(s) that address rhythm activity, phlegm, and blood sugar. Continue a TCM formula that recovers after illness and within 2 weeks after weaning from nitrates and pharmaceutical drugs; and incorporate formula(s) that address rhythm activity, phlegm, and blood sugar. Patient experiences a stressor or the effects of an illness that raises blood pressure; or causes exhaustion from physical strain, breathing difficulty, and lower body edema. Some patients may need to live on a fluid restriction, including drinks and food, of a minimum of 1 L up to a maximum of 2 L daily. Some patients may need to live on a salt restriction to assist with the desire to drink more fluids.

Prevention Stage

Condition

Purpose of treatment

Hypertension

Implementing a strategy 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. Reducing diastolic blood pressure in increments of 2 mmHg to help decrease the risk of stroke by 15% and the risk of coronary heart disease by 6%. Those groups include patients with a family history of hypertension, obesity, and

Herbal formula Integrative treatment herbs and Pharmaceutical only drugs drugs only

14

Chapter 1 Establishing a therapeutic rationale during treatment

dcontinued

Condition

Hyperlipidemia

Peripheral vascular disease

Atherosclerosis

Purpose of treatment weight gain with physical inactivity; excessive consumption of sugar, sodium, and alcohol; multigenerational American citizens with a black (African) ancestry; and physical inactivity. Patients 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. To help with male virility, leg swelling, back pain, and overall energy. Practitioners may find among other therapeutic principles that the TCM differentiations of blood deficiency and stagnation are obvious. Assisting the patient by balancing yin and yang, qi, and building blood will help them to notice marked positive differences in their well-being over time. Assisting 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

Herbal formula Integrative treatment herbs and Pharmaceutical only drugs drugs only

Chapter 1 Establishing a therapeutic rationale during treatment

Diabetes

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. 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. Use caution with modifying formulas with herbs, kushen, milk weed, lily of the valley, hawthorn, mao di huang, shu di huang, sheng di huang, and other cardiotonic herbs with glycosides as part of plant or natural substance constituents. Prophylaxis due to diagnosis of very high cholesterol levels plus age and weight, other steadily developing cardiovascular symptoms, positive stress test, and PCI result of 50% or less occlusion 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 h before or after pharmaceutical drug doses. To help the body utilize and regulate normal use of glucose in the blood, normal lipid accumulation and metabolism, sufficient blood content and levels. Single or simple herb combinations and nutritional supplementation can be used in daily health tonics, short-term regimens, and culinary use to enhance dietary practices. Understanding of the body constitution and proper timing is important. Patients must be educated on how to predict peak action of insulin and other symptoms and be guided about how to create a lifestyle to remain literate and proactive.

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dcontinued

Condition

Diuretics

Purpose of treatment Monitored through tapering down of prescribed pharmaceutical drugs. It is important to educate them about properly utilizing food and medicine. They should be educated about snacks and meals, and when and how to integrate single or simple herb combinations and nutritional supplements with oral or injected pharmaceutical drugs. Continue a TCM 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. Continue a TCM 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. Patient experiences a stressor or the effects of an illness that raises the blood pressure, causes exhaustion from physical strain, breathing difficulty, and lower body edema. Some patients may need to live on a fluid restriction, including drinks and food, of a minimum of 1 L up to a maximum of 2 L daily. Some patients may need to live on a salt restriction to assist with the desire to drink more fluids Patients should monitor weight daily before meals. Concern is for weight gain or loss of more than 3 lb daily or 5 lb weekly.

Herbal formula Integrative treatment herbs and Pharmaceutical only drugs drugs only

Chapter 1 Establishing a therapeutic rationale during treatment

Further Reading 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. Bosu WK, Aheto JMK, Zucchelli E, Reilly ST. Determinants of systemic hypertension in older adults in Africa: a systematic review. BMC Cardiovasc Disord. 2019;19(1):173. https://doi.org/10.1186/s12872-019-1147-7. Published 2019 Jul 22. Bosu WK, Reilly ST, Aheto JMK, Zucchelli E. Hypertension in older adults in Africa: a systematic review and meta-analysis. PLoS One. 2019;14(4): e0214934. https://doi.org/10.1371/journal.pone.0214934. Published 2019 Apr 5. Chimberengwa PT, Naidoo M. A description of community-based participatory research of hypertension awareness, prevention and treatment in a district of Matabeleland South Province, Zimbabwe. Afr J Prim Health Care Fam Med. 2019;11(1):e1ee9. https://doi.org/10.4102/phcfm.v11i1.1839. Published 2019 Jan 31. Fisher NDL, Fera LE, Dunning JR, et al. Development of an entirely remote, nonphysician led hypertension management program. Clin Cardiol. 2019;42(2): 285e291. https://doi.org/10.1002/clc.23141. Geraci G, Buccheri D, Zanoli L, et al. Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease. Exp Ther Med. 2019;17(4):3255e3263. https:// doi.org/10.3892/etm.2019.7279. Harshfield EL, Koulman A, Ziemek D, et al. An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors. J Proteome Res. 2019;18(6): 2397e2410. https://doi.org/10.1021/acs.jproteome.8b00786. Jung HJ, Kwon TH. New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus. Kidney Res Clin Pract. 2019;38(2):145e158. https://doi.org/ 10.23876/j.krcp.19.002. Kilpeläinen TO, Bentley AR, Noordam R, et al. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun. 2019;10(1):376. https://doi.org/10.1038/s41467-018-08008-w. Published 2019 Jan 22. Letourneau LR, Greeley SAW. Congenital diabetes: comprehensive genetic testing allows for improved diagnosis and treatment of diabetes and other associated features. Curr Diab Rep. 2018;18(7):46. https://doi.org/10.1007/ s11892-018-1016-2. Published 2018 Jun 13.  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. Sanyoura M, Philipson LH, Naylor R. Monogenic diabetes in children and adolescents: recognition and treatment options. Curr Diab Rep. 2018;18(8): 58. https://doi.org/10.1007/s11892-018-1024-2. Published 2018 Jun 22. Smedegaard SB, Jørgensen JO, Rittig N. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and subsequent central diabetes insipidus: a rare presentation of pituitary apoplexy. Case Rep Endocrinol. 2019;2019: 7592648. https://doi.org/10.1155/2019/7592648. Published 2019 Apr 2.

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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.

2 Partnering with compliant patients Chapter Objectives 1. To discuss medical empathy in the form of detached cognition, emotional resonance and attuning. 2. To establish a journal format for patients to remain compliant and therefore part of their own therapeutic process towards better health outcomes. 3. To discuss the different approaches and their advantages in maintaining the physician and patient relationship.

Medical empathy Within the definitions and examples of the meaning of empathy, it is implied that first, we imagine how it feels to be in another person’s situation. Many physicians practice empathy as a form of detached cognition, listening to responses and answering a patient’s directed question, with parallel judgments and introspection that may not align with patient focus. Emotional resonance is the ability to recall an event or situation and feel the same as what another person is feeling. For a physician, this ability to have empathy helps to focus attention on the needs of the patient and gives patients a sense that the doctor has experience and knows what he or she is doing. If a percentage of disease has an emotional attachment to experiencing it, then patients will look to physicians for cues of understanding. That understanding is a form of empathy, which can influence outcomes. Physicians can show empathy by explaining the clinical process, diagnoses, and therapeutic principles in ways that are not confusing. For example, what does blood stasis mean in Chinese medicine in comparison and contrast to blood stasis in western medicine? Would pulse diagnosis in Chinese medicine doom the patient to believe there is a fatal disease state in that particular body organ according to a western medicine perspective? Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00002-3 Copyright © 2020 Elsevier Inc. All rights reserved.

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A physician can also express empathy by attuning and realizing the suggestion behind nonverbal cues, especially realizing that commonly the patient’s personal life will be affected by or directly contribute to additional anxiety. Health problems, especially those that become more serious over time, can affect the patient’s home life, relationships, job performance, and so on. A physician can exercise forethought by anticipating certain emotional needs and addressing them so as to minimize and possibly diminish the influence on outcomes. For example, it is known that a patient’s inability to sleep at night is due to health and personal worries that disturb and injure shen. Patients with advancing disease states who begin to limit movement and activity, especially in the elderly, begin to eat less. Eating provides nutrition for energy for systemic functions, skin health, and wound healing in the bedridden and facilitates the intended pharmacodynamics of some herbal formulas and pharmaceutical drugs. Using the wisdom of experience to address anticipated and patient-expressed concerns can foster trust and patients’ focus on their role of adherence, compliance to treatments, being more forthcoming in their own narrative, and taking steps to amend barriers to their own healing. Finally, empathy brings meaning, purpose, and fulfillment for the physician, especially when their patients are inspired and encouraged to partner in favorable outcomes and present such evidence.

Patient compliance Beyond merely following the advice for consuming medication and other adjustments, patients should make sure they obtain copies of medical records from their patient files including hospitalizations and surgeries. They should also keep a journal chronicling daily thoughts, accomplishments, and setbacks along with medication schedules and physician appointments. A health journal helps a patient record health history, remain organized, stay healthy, and can help form the body of the patient narrative during visits to keep the physician informed about progress. The following is an example of a medical journal format:

Chapter 2 Partnering with compliant patients

Injury, symptoms of Date diagnosis

Medications: Treatment Medications: herbal plan drugs formulas

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Thoughts and Nutritional feelings for the supplements day

Physician/patient relationship The physician/patient relationship, also known as the doctor/patient relationship, is established as a patient entitlement. It builds and develops during the clinical processes of narratives, physical examination, diagnosis, and treatment. It involves good communication as a result of physician empathy and patient cooperation; patient trust, which allows them to listen to guidance; physician trust, which obligates them to provide an honest assessment of the health condition; and properly guides patient autonomy and respecting professional boundaries. Four models represent approaches in the physician/patient relationship:

Approach

Advantages

Paternalistic approach

• • • • •

Informative model Interpretive model Deliberative model

• • • •

Physician dominates. Patient complies. Usually done in emergency situations when consent is not possible or warranted. Physician provides information and discusses various treatments options. Patient takes information from the doctor and is free to make his or her own decision about his or her medical condition. Physician advises by interpreting medical information, medical records, diagnostic results, treatment options, and progress. Patient guides on what treatment options the physician can explore. Physician is only a friendly consultant and educates about options he or she recommend and endorse. Patient selects treatment similar to choosing a brand or preference that is more personalized.

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Further reading: Ahmadian Yazdi N, Bigdeli S, Soltani Arabshahi SK, Ghaffarifar S. The influence of role-modeling on clinical empathy of medical interns: A qualitative study. J Adv Med Educ Prof. 2019;7(1):35e41. https://doi.org/10.30476/ JAMP.2019.41043. Fongwa MN, Dela Cruz FA, Hays RD. African American women’s perceptions of the meaning of support groups for improving adherence to hypertension treatment: a conceptual model. Nurs Open. 2019;6(3):860e870. https:// doi.org/10.1002/nop2.266. Published 2019 Apr 1. Lall MD, Gaeta TJ, Chung AS, et al. Assessment of Physician Well-being, Part One: Burnout and Other Negative States. West J Emerg Med. 2019;20(2): 278e290. https://doi.org/10.5811/westjem.2019.1.39665. McGoon MD, Ferrari P, Armstrong I, et al. The importance of patient perspectives in pulmonary hypertension. Eur Respir J. 2019;53(1):1801919. https://doi.org/10.1183/13993003.01919-2018. Published 2019 Jan 24. Rector TS, Kubo SH, Cohn JN. Patients’ self-assessment of their congestive heart failure. Part 2: content, reliability and validity of a new measure, the Minnesota Living with Heart Failure Questionnaire. Heart Fail. 1987;3: 198e219. Roberts BW, Roberts MB, Yao J, Bosire J, Mazzarelli A, Trzeciak S. Development and validation of a tool to measure patient assessment of clinical compassion. JAMA Netw Open. 2019;2(5):e193976. https://doi.org/10.1001/ jamanetworkopen.2019.3976. Published 2019 May 3. Roberts BW, Roberts MB, Yao J, Bosire J, Mazzarelli A, Trzeciak S. Development and validation of a tool to measure patient assessment of clinical compassion. JAMA Netw Open. 2019;2(5):e193976. https://doi.org/10.1001/ jamanetworkopen.2019.3976. Published 2019 May 3. Thimmapuram JR, Grim R, Bell T, et al. Factors influencing work-life balance in physicians and advance practice clinicians and the effect of heartfulness meditation conference on burnout. Glob Adv Health Med. 2019;8. https:// doi.org/10.1177/2164956118821056, 2164956118821056. Published 2019 Jan 15. Woolf-King SE, Arnold E, Weiss S, Teitel D. "There’s no acknowledgement of what this does to people": a qualitative exploration of mental health among parents of children with critical congenital heart defects. J Clin Nurs. 2018; 27(13e14):2785e2794. https://doi.org/10.1111/jocn.14275.

3 Discussion of drug classes and types Chapter Objectives 1. Introduce drug classes and types. 2. Introduce classes of antiarrhythmic drugs and their purposes and indications. 3. Introduce inotropic drugs and their purposes and indications. 4. Introduce anticoagulants and their purposes and indications. 5. Introduce antiglycerides and their purposes and indications. 6. Introduce antihypertensives and their purposes and indications. 7. Introduce antiglycemics and their purposes and indications. 8. Introduce diuretics and their purposes and indications. 9. Introduce nitrates and their purposes and indications.

Antiarrhythmic drugs Cardiac action potentials Phase 0 Influx of sodium ions Phase 1 Inactivation of the sodium channel Phase 2 Voltage plateau causes the opening of calcium channels Phase 3 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 (CCBs) • Class V: Other or unknown mechanism of action: these include the actions of magnesium, digoxin, and adenosine.

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00003-5 Copyright © 2020 Elsevier Inc. All rights reserved.

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Chapter 3 Discussion of drug classes and types

dcontinued Antiarrhythmic drugs Cardiac action potentials 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: CCBs

• • • • • • • • • • •

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

Chapter 3 Discussion of drug classes and types

27

Class IA antiarrhythmics

Drug indications

Drug side effects

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; caution in renal failure

This drug causes ventricular problems, 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

Procainamide

Sodium and potassium channel blocker, prolongs the action potential duration of ventricular myocytes and Purkinje fibers 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

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 dentists office with complaints of bleeding gums; at their physicians office with a mix of flu-like symptoms of fever, sore throat, nausea, vomiting, and diarrhea; and may be monitored with the cardiologist for gastrointestinal bleeding, hypotension, and peripheral vasodilation. Other symptoms include:

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Chapter 3 Discussion of drug classes and types

dcontinued Drug indications

Drug side effects • 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) contractions

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%; caution in hepatic or renal diseases

This drug acts on the potassium channels and may 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

Chapter 3 Discussion of drug classes and types

Class IB antidysrhythmics Drug indications

Drug side effects

Lidocaine Sodium channel blocker, 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 for this purpose and should not be taken with lidocaine). Metabolism: Hepatic metabolism by CYP3A4 into an active metabolite Mexiletine Sodium channel blocker, 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%; caution in hepatic and renal disease

Lidocaine and Mexiletine These drugs cause the 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 • 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

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Class IC antidysrhythmics

Drug indications

Drug side effects

Flecainide

Sodium channel blocker, has negative inotropic effects, and slows conduction in all cardiac fibers • 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%; caution in hepatic and renal diseases

This drug causes symptoms of 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, which increases torsades de pointes • ST elevation in lead V1 characteristic of Brugada syndrome (also used to diagnose suspected Brugada syndrome)

Propafenone

Sodium and CCB Indications: Atrial fibrillation and life-threatening ventricular dysrhythmias Metabolism: Hepatic metabolism by CYP2D6, CYP3A4, and CYP1A2

This drug may cause drug-induced SLE syndrome in both males and females. Definitely causes symptoms of worsening heart failure, gastrointestinal symptoms, and CNS symptoms, which are dose dependent. Clinical presentations include: Heart failure:

Chapter 3 Discussion of drug classes and types

31

• Dyspnea and breathlessness • Edema • 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

Class III antidysrhythmics

Drug indications

Drug side effects

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

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

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Chapter 3 Discussion of drug classes and types

dcontinued Drug indications

Drug side effects 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

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

This drug generally causes several types of side effects. Direct reactions including bradyarrhythmias 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

Chapter 3 Discussion of drug classes and types

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; caution in renal disease so creatinine clearance is necessary and excreted unchanged by kidneys

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

Class V antidysrhythmics Drug indications

Drug side effects

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 tachycardias after failure of vagal maneuver Metabolism: Intracellular metabolism

Symptoms that resolve quickly without additional treatment: • Chest pressure • Headache and light-headiness • Dyspnea • Skin flushing ECG • Transient asystole, the treatment goal • Developing bradycardia, AV block, or sinus arrest • Atrial fibrillation

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Inotropics

Drug indications 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. Generally, inotropic drugs are medicines used for symptoms of heart failure including hypertension, angina, arrhythmia, 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 lead 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 • 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

Drug 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 • Double vision • Light sensitivity

Chapter 3 Discussion of drug classes and types

• • • •

Hypertension Arrhythmia Angina Weaken the contractions and slow down the heart rate • Reduce stress on the heart following myocardial infarction to prevent future events

Alpha/beta-adrenergic agonists Drug indications 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 Drug indications Isoproterenol • Treats torsades de pointes if treatment with magnesium fails • Treats ventricular tachycardia or fibrillation with Brugada syndrome

Anticonvulsants These drugs include benzodiazepines and are CNS (limbic and reticular formation) depressants by increasing the action of gamma aminobenzoic acid, which is a major inhibitory neurotransmitter.

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Drug indications 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

Anticoagulants These drugs are indicated for peripheral vascular disease and deep vein thrombosis (DVT), to prevent postthrombotic syndrome, prevent pulmonary embolism (PE), and reduce further health debilitation and morbidity.

Drug indications

Drugs and their purposes

These drugs help prevent thrombolytic vascular occlusion. Many of them reversibly block the active site of factor Xa, affect prothrombin time, 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. Vitamin K antagonists These drugs are coumarins, which interfere with the interaction between vitamin K and dependent coagulation factors II, VII, IX, and X. They are used both as prophylaxis and treatment of DVT and PE. Doses are adjusted according to patient weight and health condition for maintaining international normalized ratio of 2e3. Warfarin

• Apixaban: For adult patients undergoing orthopedic surgery • Betrixaban: For hospitalized and restricted/ immobile adults at risk for thromboembolic complications • Dabigatran: prevents 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

Chapter 3 Discussion of drug classes and types

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

• Rivaroxaban: For adult patients undergoing orthopedic surgery, helps and reduces risk of recurrence of blood clots

• Dalteparin: For DVT treatment • Enoxaparin: For DVT and PE treatment • Tinzaparin: For DVT treatment

Antiplatelets Drug indications Aspirin Clopidogrel Ticagrelor Prasugrel

Drug purposes These drugs are blood thinners, which prevent blood from forming atheromas and other clots. This drug is used to prevent clots from forming inside of artery stents. These drugs are used to prevent clots from forming inside of artery stents. Can be taken with aspirin.

Antiglycerides Statins are a class of drugs used in primary prevention and for treatment of excess cholesterol levels and balance of LDL and

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Chapter 3 Discussion of drug classes and types

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 chances of infarction by 40% and heart diseaseerelated 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 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.

Drug indications 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.

These patients commonly experience side effects of statin use which include: Shen and blood deficiency disturbances: • Difficulty sleeping with drowsiness during active periods, active during sleep periods • Headache • Dizziness • Memory loss

Chapter 3 Discussion of drug classes and types

Ezetimibe This drug reduces absorption of cholesterol in the small intestines and reduces LDL levels. Bile acid sequestrants These drugs bind to bile acid in the small intestines to lower it, because it requires cholesterol to create it. 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. 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 preventing ApoB-containing lipoproteins such as LDL and cholesterol.

39

• Mental confusion Musculoskeletal side effects: • Elevated creatinine kinase, which causes muscle inflammation • 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: ooverall 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

Antihypertensives

Drug indications Adrenergic agent

Aldosterone antagonists

Drug purposes This drug is for mild hypertension and is often used with other antihypertensive drugs for more severe hypertension. These selective drugs compete with aldosterone receptor sites, reducing blood pressure and sodium reabsorption.

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Chapter 3 Discussion of drug classes and types

dcontinued Drug indications Alpha blockers

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. These drugs limit the amount or rate of calcium allowed into heart muscle and arteries so that those tissues will relax, which lowers blood pressure; generally used to treat hypertension, arrhythmia, and angina. They are either dihydropyridines or nondihydropyridines. Some bind to L-type calcium channels causing vasodilatation and a decrease in blood pressure. Others bind to Ltype calcium channels in the sinoatrial and atrioventricular node. These drugs are often suggested for American patients of distant African ancestry, patients with diabetes including kidney disease, and the elderly. Other medicines often taken with calcium antagonists for hypertension are ACEIs, ARBs, and diuretics. Drug classes of CCBs and their cardiovascular target Dihydropyridines Arteries Benzothiazepines Heart muscle Arteries Phenylalkylamines Heart muscle Commonly prescribed CCBs • amlodipine (Norvasc) • Diltiazem (Cardizem): also for arrhythmias and angina pectoris • Felodipine (Plendil)

Drug purposes These drugs selectively block postsynaptic alpha1adrenergic 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. Adverse patient presentation includes toxicity and overdose. Initial blood lab test for toxicity will reveal hyperglycemia, hypokalemia, and acidosis. Physical examination of a patient can mimic the effects of certain acupuncture treatments such as immediate hypotension, slowed heart rate, and subdued consciousness. Signs and symptoms of toxicity may include: • Dizziness or lightheadedness • Syncope • Diaphoresis • Dyspnea • Confusion • Seizure • Headache • Chest pain • Palpitations • Nausea and vomiting • Flushing • Peripheral edema Symptoms of overdoses are according to medication delivery type: immediate-release pills or extended release pills. Immediate release pill overdose reaction includes immediate onset of: • Hypotension • Bradyarrhythmia • Cardiac arrest Extended-release pill overdose reactions include delayed onset of: • Dysrhythmias • Shock • Sudden cardiac collapse • Bowel ischemia

Chapter 3 Discussion of drug classes and types

• Isradipine • Nicardipine (Cardene) • Nifedipine (adalat CC) • Nimodipine (Nymalize) • Nitrendipine • Veralan: also for arrhythmias and angina pectoris Beta Blockers This drug is part of popular drug for male sexual virility. It is also prescribed for hyperthyroid and other expanded uses. It is known to cause hypoglycemia, hypotension, bradycardias, and other types of arrhythmias. Beta-1 receptor Blockers These drugs block beta-1 receptors, act selectively, yet can act nonselectively if given at higher doses. When weaning off of this drug, the doses should be gradually reduced over several weeks.

ACEIs These drugs are used in patients with hypertension, chronic kidney disease, and proteinuria. They suppress the renin-angiotensin-aldosterone system by preventing the conversion of angiotensin I to angiotensin II and blocking the major pathway of the degradation of bradykinin by inhibiting ACE. They are often considered strong when used alone, without a diuretic, but can be combined with one. ARBs 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 II induced vasoconstriction, reduce sodium retention, and reduce aldosterone release. ARBs are used alone or often combined with a diuretic.

Aldosterone antagonists Beta blockers (Also known as beta-adrenergic blocking agents) Bisoprolol (zebeta) Carvedilol (Coreg) Carvedilol CR (Coreg CR) Toprol XL If Channel Blocker (or inhibitor) Eplerenone (inspra) Hydralazine and isosorbide dinitrate (Bidil) (targeted to benefit African Americans with heart failure) Ivabradine (Corlanor) Metoprolol succinate (Toprol XL) Spironolactone (aldactone) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil, zestril) Perindopril (aceon) Quinapril (accupril) Ramipril (altace) Trandolapril (Mavik) ARNIs Candesartan (atacand) Losartan (Cozaar) Sacubitril/valsartan Valsartan (Diovan)

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Chapter 3 Discussion of drug classes and types

Antiglycemics For all diabetics controlling the diseases involves utilization of insulin. Patients with type 2 diabetes are often prescribed two classes of oral hypoglycemic agents (OHAs) because they face not producing enough insulin and need to increase insulin output, and they also have insulin resistance and need to improve how their body distributes and utilizes insulin.

Injected drugs

Drug indications Insulin output increasers These drugs help with secretion of insulin in the beta cells of the islets of langerhans in the pancreas. These drugs commonly lose effectiveness during long-term use. Side effects include hypoglycemia and weight gain. Sulfonylurea group These drugs have a relatively slow release and distribution within the body. Nonsulfonylurea group These drugs cause weight gain but respond faster and with shorter duration than the sulfonyl group. Dipeptidyl Peptidase-4 inhibitors These drugs have a weaker effect than the sulfonylurea and nonsulfonylurea groups, but less frequently cause hypoglycemia and weight gain. Alpha-glucosidase inhibitors These drugs have the weakest effect on the control of diabetes, but reduce absorption of glucose in the small intestine, though the side effects are gastrointestinal problems including nausea and diarrhea. Glucose output and uptake reducers These drugs decrease glucose production and accumulation in the liver and increase sensitivity and utilization of glucose in the muscle cell. It does not cause weight gain and hypoglycemia like OHA drugs. The disadvantages are vitamin B12 blocking, which inhibits red blood cell production and gastrointestinal symptoms of nausea and bowel disturbances. • Metformin Insulin Resistance reducers These drugs have a weaker effect than metformin but still decrease glucose production and accumulation in the liver and increase sensitivity. The emphasis is to increase utilization of glucose in the muscle cell. • Thiazolidinediones Glitazones

Chapter 3 Discussion of drug classes and types

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Drug indications Noninsulin injected drugs These drugs are often prescribed in conjunction with OHAs to stimulate insulin secretion, reduce glucose production, yet enhance utilization, reduce excessive weight gain by helping with appetite control and prolonging stomach emptying time, and reduce side effects that affect the cardiovascular system. 1. Glucagon-Like peptide analogues: given once weekly instead of traditional twice daily 2. Pramlintide acetate 3. SGLT2 inhibitors: Inhibit kidney glucose reabsorption 4. Incretin 5. Glucokinase activators

Diuretics

Drug indications

Side effects

Loop Diuretics These drugs are commonly used to control the retention of urine volume and are more commonly prescribed for decreased glomerular filtration rate or heart failure. They act on the ascending limb of the loop of Henle, reducing reabsorption of calcium and magnesium and inhibiting the sodium/potassium/chloride (Naþ/ Kþ/2Cl) cotransporter in the thick ascending loop of Henle, also known as 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. • Bumex (bumetanide) • Edecrin (ethacrynic acid)

• Fatigue, muscle cramps, or weakness from low potassium levels • Dizziness or lightheadedness • Numbness or tingling • Heart palpitations • Gout • Depression • Irritability • Urinary incontinence • Gynomastic appearance and impotence in men • Breast tenderness, hirsutism, loss of sexual desire, and

Symptoms that require emergency assistance Respiratory concerns: • Dyspnea during activity, at rest, and while asleep • Wheezing • Difficulty breathing • Persistent cough that is either dry and hacking or bloodtinged expectoration Fluid metabolism: • Swelling in the legs, ankles, or feet • Profuse urination or increased frequency resulting in fully voiding the bladder, especially at night • Sudden and considerable weight gain or loss • Symptoms connected to medication side effects

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Chapter 3 Discussion of drug classes and types

dcontinued Drug indications • Demadex (torsemide) • lasix (furosemide) 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. • Inspra (eplerenone) • Dyrenium (triamterene) • Aldactone (spironolactone) • Midamor (amiloride) • CaroSpir (spironolactone) 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. • Amiloride (Midamor Chlorthalidone Hygroton) • Bumetanide (Bumex) • Chlorothiazide (Diuril) • Furosemide (Lasix) • Hydrochlorothiazide (HCTZ): (Esidrix, Hydrodiuril) • Indapamide (Lozol) • Metolazone (Zaroxolyn) • Torsemide (Demadex) • Triamterene (Dyrenium)

Side effects menstrual problems in women • Allergic reactions related to sulfa drug allergies

Symptoms that require emergency assistance Cardiac concerns: • Pulse is slow or rapid • Heartbeat is distinctly felt in the chest and sensation is pounding and irregular or steady • Feeling tired or weak with a high pulse rate Patients should monitor weight daily before meals. Concern is for weight gain or loss of more than 3 lb daily or 5 lb weekly. • Potassium • Magnesium • Vitamin C

Chapter 3 Discussion of drug classes and types

Nitrates Nitrates are drugs used to treat advanced and serious cardiovascular disease caused by factors that weaken functioning. They can also be used at the time of emergency when one or more factors have caused the vessels to constrict to the point that the heart is overworked to the point of ultimate exhaustion. They immediately cause the vascular system to dilate so that the oxygen-rich blood can flow, and the heart can work less and at a more optimal pace. When used as a prophylactic or in chronic treatment, nitrates can help keep vessels dilated so that oxygen, vital components, and nutrients and drugs that prevent or treat blood disorders can help keep it flowing through. Use with caution with other pharmaceutical drugs for diseases associated with impending or confirmed heart failure.

Nitrate use in heart failure Nitrate

Delivery

Isosorbide dinitrate

Oral

Isosorbide mononitrate Nitroglycerin

Oral Oral Parenteral Sublingual Topical transdermal

Angina Pectoris

Congestive Heart Failure

Hypertension

Prophylactic Acute Chronic Chronic

Chronic

Chronic

Acute Chronic

Not indicated

Not indicated

Not indicated

Chronic

Chronic

Acute Chronic

Prophylactic Acute Chronic

Further Reading AlHabeeb W, Al-Ayoubi F, AlGhalayini K, et al. Saudi Heart Association (SHA) guidelines for the management of heart failure. J Saudi Heart Assoc. 2019; 31(4):204e253. https://doi.org/10.1016/j.jsha.2019.06.004. Clark AL, Kalra PR, Petrie MC, Mark PB, Tomlinson LA, Tomson CR. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019;105(12):904e910. https://doi.org/10.1136/heartjnl2018-314158. de Boer RA, De Keulenaer G, Bauersachs J, et al. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap

Myocardial Infarction

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Chapter 3 Discussion of drug classes and types

by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology. Eur J Heart Fail. 2019;21(3): 272e285. https://doi.org/10.1002/ejhf.1406. Mordi IR, Santema BT, Kloosterman M, et al. Prognostic significance of changes in heart rate following uptitration of beta-blockers in patients with suboptimally treated heart failure with reduced ejection fraction in sinus rhythm versus atrial fibrillation. Clin Res Cardiol. 2019;108(7):797e805. https:// doi.org/10.1007/s00392-018-1409-x. Saito T, Nah J, Oka SI, et al. An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia. J Clin Invest. 2019;129(2):802e819. https://doi.org/10.1172/JCI122035. Wang CC, Wu CK, Tsai ML, et al. 2019 Focused update of the guidelines of the taiwan society of cardiology for the diagnosis and treatment of heart failure. Acta Cardiol Sin. 2019;35(3):244e283. https://doi.org/10.6515/ ACS.201905_35(3).20190422A. Yang X, He T, Han S, et al. The role of traditional Chinese medicine in the regulation of oxidative stress in treating coronary heart disease. Oxid Med Cell Longev. 2019;2019:3231424. https://doi.org/10.1155/2019/3231424. Published 2019 Feb 24.

4 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 dates far into antiquity. The Yellow Emperor is considered by many scholars to be a mythological deity and actual ruler between 2698 and 2598 BC. Through discussions with advisors known as ministers about life and health he 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, 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 BC) of the Western and Eastern Zhou Dynasty (1100e221 BC) and Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00004-7 Copyright © 2020 Elsevier Inc. All rights reserved.

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

Chapter 4 Traditional Chinese medicine

Period of middle ages in China

(AD 220e580)

Three kingdoms Period Western and Eastern Jin Dynasty Southern Dynasty Northern Dynasty

(AD (AD (AD (AD

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.

Chapter 4 Traditional Chinese medicine

4. You You Xin Shu (New Book of Pediatric Influence). This book described inspection and examination of children for genetic and acquired illnesses. 5. Cun Zhen Tu (Anatomical Atlas of Truth). This book described anatomy based on performing autopsies.

Ming Dynasty (AD 1368e1644) 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.

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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 treaties 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. 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.

20th century China (AD 1912e1999) 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

Chapter 4 Traditional Chinese medicine

as well. Epidemic plaques 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 antieChinese 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 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 1980 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 1966 and 76 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 to comprise 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.

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21st 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.

Constitutional theories

1a 9 Body constitutions in Chinese medicine Constitution

Symptoms

Diet

Lifestyle

Neutral

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

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

Moderate and balanced and free of oily and spicy food More qi food and nutrition that invigorates the spleen Avoid garlic, radishes, and cilantro 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 More foods that cool such as salads and fresh fruits No foods that heat such as lamb

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

Yang deficient

Yin deficient

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

• • • •

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

Chapter 4 Traditional Chinese medicine

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 food that promotes blood circulation No fatty meat or dairy products Eat a bland diet Reduce or avoid sweet food and drinks Include more seaweed in the diet

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

Blood stasis

Phlegm dampness

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• Exercises and activities that promotes blood circulation • Avoid risk factors for diabetes • Avoid risk factors for metabolic syndrome • Avoid risk factors for cardiovascular diseases • Avoid a sedentary lifestyle • 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

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1b Basic seasonal habits for cardiovascular disease prevention Spring

Summer

Autumn

Winter

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. 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.

Basic female constitutional

General stages of infant and childhood constitution

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General stages of teenage and young adult constitution

General stages of the middle-age constitution

General geriatric constitutions

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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.

1d Constitution

General prevention suggestions

Basic male constitutional

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. 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. Diet: Foods, drinks, herbs, and supplements that establish the balance of yin 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.

Basic female constitutional

General stages of infant and childhood constitution

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1ddcontinued Constitution

General prevention suggestions

General stages of teenage and young adult constitution

Diet: Foods, drinks, herbs, and supplements that maintain the balance of yin 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 builds and strengthens muscles and tissues and regulates fat. Diet: Foods, drinks, herbs, and supplements that repair the imbalance of yin 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. 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.

General stages of the middle-age constitution

General geriatric constitutions

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 and 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

Yang deficiency constitution

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Yang deficiency constitution

Blood deficiency constitution

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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.

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

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1g Constitution Yin deficiency constitution

Yang deficiency constitution

Qi deficiency constitution

Blood deficiency constitution

Recovery suggestions for stagnation, stasis, and excess constitutions 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, 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 build 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 create a lot of brute effort and overstrain.

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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, marijuana, OTC remedies, prescription and illicit recreational drugs, which tend to stagnate liver qi. Exercise: Avoid activities that create a lot of 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, which 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 create 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 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 create a lot of 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 infection. 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.

Blood stasis constitution

Damp phlegm constitution

Damp heat constitution

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

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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. • 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 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 h, 2 h before or after eating a meal. Recovery: Take every 4e6 h until well-being is restored.

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1i Decoction dosage suggestions according to constitution Constitution

Prevention/Recovery

Acute

Chronic

Teenage to young adult Age 13e30 Middle age 40e60s 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

Most common herbs used in Chinese medicine cardiology

25 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

Blood pressure reduction Antimicrobial, immune builder, basal temperature regulation, lipid, excess fluid and blood pressure reduction

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dcontinued 25 Most commonly used herbs in traditional Chinese medicine cardiology Herb

Main active constituents

Significance

Gan cao

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

Lipid reduction, antiinflammatory, antidiabetic, antiallergen, blood pressure reduction

Mai men dong Hong hua

Chuan xiong Ru Xiang Huang lian Mu dan pi

Ban lan gen Dan shen

Suan zao ren He shou wu Yu jin Huang qi Du zhong Ren shen

Rou cong rong

a- and b- boswellic acid, a- and bphellandrine, olibanoresene, pinene Berberine, coptisine, ferulic acid, palmatine, jatrorrhizine Paeonol, camperterol

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

Betulinm jujuboside, saponins, betulic acid, ebelin lactone Chrysophanic acid, lecithin d- Campene, a- and b- curcumene, tumerone D- b-asparagine, b-sitosterol choline, betaine Alkaloids, potassium, aucubin, glycosides, vitamin C Panaxadiol, ginsenin, panaenic acid, nicotinic acid Alkaloids

Blood pressure reduction, antiinflammatory Lipid reduction, blood pressure reduction, invigorates blood Invigorates blood circulation, reduces blood pressure Invigorates blood circulation, reduces chest pain 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 Reduces or stops arrhythmia, reduces lipids, increases the immune system, reduces stress Blood pressure reduction

Chapter 4 Traditional Chinese medicine

Antihypertensive formulas

Traditional Chinese medicine formulas for hypertension Herbal medicine

Action

Modified gambirplant branch formula Modified yang hyperactivity check with 7drugs 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, chest oppression Stabilizes blood pressure while recovering from dryness, exhaustion, and headache Reduces blood pressure, nourishes blood

Antiarrhythmic formulas

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

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Antithrombotic formulas 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

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

Shen fu decoction Gui pi decoction

Antibiotic formulas 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

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

Zhi gan cao decoction Shen fu decoction Gui pi decoction

Antilipid formulas Traditional Chinese medicine formulas for arrhythmia Herbal medicine

Action

Yue jian cao you jiao wan Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling

Invigorates blood, dispels phlegm Invigorates blood, dispels phlegm Clears toxic bacterial and viral heat Clears toxic bacterial and viral heat

Chapter 4 Traditional Chinese medicine

Xi huang wan

Clears heat, invigorates blood, protects the heart Recovers from illness, regulates heart functioning Recovers after an illness, warms yang Nourishes blood

Zhi gan cao decoction Shen fu decoction Gui pi decoction

Antiglycemic formulas Traditional Chinese medicine formulas for arrhythmia Herbal medicine

Action

Yu quan wan Zuo gui wan Liu wei di huang wan Zhi gan cao decoction

Nourishes kidney yin, clears heat Nourishes kidney yin, increases jing Nourishes kidney and liver yin, increases jing Recovers from illness, regulates heart functioning Recovers after an illness, warms yang Nourishes blood

Shen fu decoction Gui pi decoction

ACE inhibitor formulas Traditional Chinese medicine formulas Herbal medicine

Action

Xue fu zhu yu tang

Invigorates resolves Invigorates resolves Invigorates resolves Invigorates resolves Invigorates resolves

Mao dong qing jiao nang Huo xue tong mai pian Su xiao jiu xin wan Dan shen yin

blood, opens channels, dredges liver, chest oppression, relieves pain blood, breaks blood stasis, calms shen, chest oppression, opens orifices blood, opens channels, dredges liver, chest oppression, relieves pain blood, breaks blood stasis, calms shen, chest oppression, opens orifices blood, breaks blood stasis, calms shen, chest oppression, opens orifices

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Diuretic formulas Traditional Chinese medicine formulas as diuretics Herbal medicine

Action

Modified wu ling san

Eliminates dampness, dispels phlegm, moves fluid Eliminates dampness, dispels phlegm, moves fluid

Modified huang ji huang qi wan

Further Reading 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. Edinburgh University Press Ltd; 1993 [Bailey P, Trans]. State Administration of TCM. Advanced textbook on traditional Chinese medicine and pharmacology. New World Press; 1995.

5 Nutritional supplements Chapter Objectives 1. Introduce the history of nutritional supplementation in the United States. 2. Recognize the government regulation of nutritional supplements. 3. List the nutritional constituents, benefits, and cautions of various antihypertensive nutrients. 4. List the nutritional constituents, benefits, and cautions of various antiarrhythmic nutrients. 5. List the nutritional constituents, benefits, and cautions of various antithrombotic nutrients. 6. List the nutritional constituents, benefits, and cautions of various antibiotic nutrients. 7. List the nutritional constituents, benefits, and cautions of various antilipidemic nutrients. 8. List the nutritional constituents, benefits, and cautions of various angiotensin-converting enzyme inhibitor nutrients. 9. List the nutritional constituents, benefits, and cautions of various diuretic nutrients.

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.

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00005-9 Copyright © 2020 Elsevier Inc. All rights reserved.

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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 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

Chapter 5 Nutritional supplements

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 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.

Regulation 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 1970 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

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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 plant-based 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. 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

Chapter 5 Nutritional supplements

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.

Antihypertensive nutrients 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.

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

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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

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

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

Antiarrhythmic nutrients 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

Coenzyme Q10 Benefits: Heart, muscle, liver, and lungs; improves glycemic index, myocardial energy Caution: Body stores 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

Magnesium sulfate Benefits: Used in magnesium deficiency, treatment of torsade de pointes, and refractory ventricular fibrillation

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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.

Antithrombotic nutrients 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. Benefits: Increases prothrombin time to prevent coagulation Caution: Careful use with anticoagulant drugs

Essential fatty acids Origin: Essential fatty acids 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

Chapter 5 Nutritional supplements

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 problem; may cause mild nausea and bloating

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

Antilipidemic nutrients Alpha lipoic acid Nutritional constituents: Lipoic acid

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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

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

Chapter 5 Nutritional supplements

Caution: May cause nausea, increase blood sugar levels, and 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

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

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 B6 may cause disfiguring skin lesions, for 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

Alpha-lipoic acid Nutritional constituents: Lipoic acid

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Benefits: Targets nerve cells, kidney, and liver; lowers blood pressure, prevents cell damage to improve insulin use, and helps reduce neuropathy pain Caution: May lower blood sugar too much; avoid in pregnancy and nursing

Berberine Benefits: Reduces excess blood sugar, alleviates neuropathy pain, and improves insulin utilization Caution: May cause gastrointestinal problems with high doses

Chromium Benefits: Production, storage, and secretion of insulin; blood sugar diffuse into cells Caution: Long-term use may cause kidney issues in patients with diabetes.

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

Melatonin Nutritional constituents: Fruits and vegetables Benefits: (indirect) Helps with inducing sleep, which assists with insulin production and glucose reduction Caution: May raise glucose levels in some patients

Omega-3 fatty acids Nutritional constituents: Vitamins A, D, fish oils, flax seed, primrose, borage, and flaxseed oils Benefits: Lower triglycerides, raises HDL, may not affect blood glucose or total cholesterol Caution: May raise LDL, or interfere with warfarin and blood pressure medicines

Probiotics Nutritional constituents: Lactobacillus, bifidobacterium

Chapter 5 Nutritional supplements

Benefits: Lowers glucose levels and insulin Caution: May cause bloating

Vanadium Benefits: Production, storage, and secretion of insulin; blood sugar diffuse into cells Caution: Long-term use may cause kidney issues in patients with diabetes

Vitamin B-1 Nutritional constituents: Thiamine (water soluble), benfotiamine (lipid soluble). Benefits: Blood vessels, blood sugar, heart functioning

Vitamin D Nutritional constituents: Vitamins A, D, fish oils, flax seed, primrose, borage, and flaxseed oils Benefits: Insulin function, heart function, kidney function Caution: Good source is from exposure to sunlight; some patients may experience skin damage with prolonged exposure

Angiotensin-converting enzyme inhibitor nutrients 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

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

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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

Magnesium sulfate Benefits: Used in magnesium deficiency, treatment of refractory ventricular fibrillation

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

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

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

Vitamin C Nutritional constituents: Ascorbic acid Benefits: Heart, kidneys, and muscle; improves type 2 insulin utilization in the elderly, assists adrenal activity for filtration of fluids from the kidneys

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Caution: May cause gastrointestinal disturbances when taken with paracetamol

Further Reading Hollanders JJ, Kouwenhoven SMP, van der Voorn B, van Goudoever JB, Rotteveel J, Finken MJJ. The association between breastmilk glucocorticoid concentrations and macronutrient contents throughout the day. Nutrients. 2019;11(2):259. https://doi.org/10.3390/nu11020259. Published 2019 Jan 24. Jin Q, Black A, Kales SN, Vattem D, Ruiz-Canela M, Sotos-Prieto M. Metabolomics and microbiomes as potential tools to evaluate the effects of the mediterranean diet. Nutrients. 2019;11(1):207. https://doi.org/10.3390/ nu11010207. Published 2019 Jan 21. Kedia-Mehta N, Finlay DK. Competition for nutrients and its role in controlling immune responses. Nat Commun. 2019;10(1):2123. https://doi.org/10.1038/ s41467-019-10015-4. Published 2019 May 9. € hbeck G, Escalada J. Impact of nutritional changes on Perdomo CM, Fru nonalcoholic fatty liver disease. Nutrients. 2019;11(3):677. https://doi.org/ 10.3390/nu11030677. Published 2019 Mar 21.  Pivk Kupirovic U, Miklavec K, Hribar M, Kusar A, Zmitek K, Pravst I. Nutrient profiling is needed to improve the nutritional quality of the foods labelled with health-related claims. Nutrients. 2019;11(2):287. https://doi.org/10.3390/ nu11020287. Published 2019 Jan 29. Serra-Majem L, Luz Fernandez M. Nutrients 2009e2019: the present and the future of nutrition. Nutrients. 2019;11(1):88. https://doi.org/10.3390/ nu11010088. Published 2019 Jan 4.

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6 Pharmaceutical drugs Chapter Objectives 1. Introduce pharmacology and the creation of drugs as a therapeutic tool against various diseases. 2. Recognize the ancient history and contributions of various cultures around the world that provided a framework for modern pharmacology. 3. Introduce modern pharmacology and the scientists who contributed methods we use today. 4. Introduce the therapeutic index, which guides the preparation and administration of pharmaceutical drugs, herbs, and their formulations to act upon the cardiovascular system according to genomics and posology.

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:

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00006-0 Copyright © 2020 Elsevier Inc. All rights reserved.

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Pharmacodynamics: the effects of chemicals on a biological system of receptors 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

Chapter 6 Pharmaceutical drugs

• 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

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.

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• 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. • 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.

Chapter 6 Pharmaceutical drugs

Ostwald 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. • 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.

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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) • 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 Cucurull-Sanchez L, Chappell MJ, Chelliah V, et al. Best practices to maximize the use and reuse of quantitative and systems pharmacology models: recommendations from the United Kingdom quantitative and systems pharmacology network. CPT Pharmacometrics Syst Pharmacol. 2019;8(5): 259e272. https://doi.org/10.1002/psp4.12381. Hao J, Hu H, Liu J, et al. Integrated metabolomics and network pharmacology study on immunoregulation mechanisms of Panax ginseng through macrophages. Evid Based Complement Alternat Med. 2019;2019:3630260. https://doi.org/10.1155/2019/3630260. Published 2019 Jun 25. Helmlinger G, Sokolov V, Peskov K, et al. Quantitative systems pharmacology: an exemplar model-building workflow with applications in cardiovascular, metabolic, and oncology drug development. CPT Pharmacometrics Syst Pharmacol. 2019;8(6):380e395. https://doi.org/10.1002/psp4.12426. Schmidt S, Kim S, Vozmediano V, Cristofoletti R, Winterstein AG, Brown JD. Pharmacometrics, physiologically based pharmacokinetics, quantitative systems pharmacology-what’s next?-joining mechanistic and epidemiological

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approaches. CPT Pharmacometrics Syst Pharmacol. 2019;8(6):352e355. https://doi.org/10.1002/psp4.12425. Uemura N. From molecule to patient: building bridges not walls with clinical pharmacology and translational medicine. Clin Transl Sci. 2019;12(2):84. https://doi.org/10.1111/cts.12628. Zhang J, Zheng C, Yuan S, et al. Uncovering the pharmacological mechanism of Chaibei Zhixian decoction on epilepsy by network pharmacology analysis. Evid Based Complement Alternat Med. 2019;2019:3104741. https://doi.org/ 10.1155/2019/3104741. Published 2019 May 12. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional chinese medicine: review and assessment. Front Pharmacol. 2019;10:123. https://doi.org/10.3389/fphar.2019.00123. Published 2019 Feb 21.

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7 Treating according to disease stages Chapter Objectives 1. Introduce the treatment of patients with hypertension and arrhythmia. 2. Introduce the treatment of patients with hypertension and arrhythmia with nutritional supplements, traditional Chinese medicine formulas, and pharmaceutical drugs according to the acute-stage vascular diseases as seen in integrative cardiovascular Chinese medicine. 3. Introduce the treatment of patients with hypertension and arrhythmia with nutritional supplements, traditional Chinese medicine formulas, and pharmaceutical drugs according to the chronic stage. 4. Introduce the treatment of patients with hypertension and arrhythmia with nutritional supplements, traditional Chinese medicine formulas, and pharmaceutical drugs according to the recovery stage. 5. Introduce the treatment of patients with hypertension and arrhythmia with nutritional supplements, traditional Chinese medicine formulas, and pharmaceutical drugs according to the prevention stage.

Acute stage Blood pressure 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 normal blood pressure levels or regular life. Nutrients: One or all • Alpha lipoic acid (ALA) • Cod liver oil • Coenzyme Q-10 • Chromium • Magnesium Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00007-2 Copyright © 2020 Elsevier Inc. All rights reserved.

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• • • • •

Herbal formulas: 1e3 Modified yang hyperactivity check with 7-drugs formula Modified liver subduing and wind stopping formula Modified blood pressure reducing decoction Modified qi replenishing and yin nourishing formula Modified cardiotonic formula

Arrhythmia As already inferred in Chapter 5, 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 traditional Chinese medicine 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 of 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 of medications without any trouble. Patients will present to the clinic for herbal medicines while weaning off of current medications. Their reasons are 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, which 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 up-front 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

Chapter 7 Treating according to disease stages

zaps. These patients will open capsules to count out granules and titrate dosages over time, usually between 6 and 24 months of continued prescription filling. Under very close supervision, if it is indicated that patients taking SSRIs and MAOIs take a course of natural medicines, caution about any with serotonin activity and monitor for mood and behavior problems, which could result in emergency room visits. The second concern is about patients who present to the clinic with symptoms they wish treated with traditional Chinese medicine (TCM), and are currently taking prescription drugs that have serious side effects or toxicities, or patients have overmedicated themselves in the attempt to alleviate worsening symptoms when scheduling a visit with their physician is not possible. For antidotes to a suspected overdose presenting in the clinic: • Use 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, helping to control blood sugar and while weaning completely off of medications consider the following.

Nutrients: One or all • • • • • • • •

Cod liver oil L-carnitine Coenzyme Q-10 Chromium Magnesium Potassium Vitamin B6 L-5-hydroxytryptophan (5-HTP)

Antithrombotics 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 of peripheral vascular disease and deep vein thrombosis.

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Atherosclerotics Patients at risk of 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.

Antiglycemics The general role of TCM and nutrients when initiated during acute or chronic stages is to help control and regulate blood sugar and excess lipid accumulation and metabolism, and to fortify blood and energy levels. Complicated combinations of herbal formulas and nutritional supplementation can be used either in therapeutic concentrations for oral and topical use or in weaker concentration for culinary use to enhance dietary practices. During the acute stage, patients should understand their body constitution and proper timing. They should know how to predict peak action of insulin and be guided about when snacks, meals, herbs, and nutritional supplements alone or integrated with oral and injected pharmaceutical drugs are indicated. Further, symptoms that hinder sexual recreation and procreation such as vaginal dryness, erectile dysfunction, and menstrual problems could experience improvement as the symptoms associated with hyperglycemia improve back to normal. During chronic stages that confirm diabetes diagnosis, patients can present with at least two other common occurrences concerning glycemic levels. The first is diabetic dermopathy. This condition involves the skin, and complaints range from itchiness, flakiness, and acanthosis nigricans of the neck, back arm pits, elbows, knuckles, and knees to hemorrhage and erosion ulcers that are often complicated by fungal and bacterial infections. The second is hypoglycemia. This happens in patients who are using injected or oral insulin and can occur in patients with diabetes for a variety of reasons including insulin resistance and lack of insulin production. Treatment strategy must include the type and stage of the diabetes and body constitution. Patients should understand proper timing, such as how

Chapter 7 Treating according to disease stages

to predict peak action of insulin when indicated snacks, meals, herbs, and nutritional supplements can be integrated with oral or injected pharmaceutical drugs. Patients with chronic and confirmed diabetes type 1 and 2 frequently monitor for several complications including diabetic ketoacidosis (DKA). DKA is preventable but when it does occur symptoms are typically dehydration with elevated glucose levels. They are hospitalized to rehydrate, restore electrolytes, and bring elevated glucose levels under control and stabilized. For patients with uncontrollable diabetes, those who are noncompliant, with DKA or kidney disease, herbs and nutrients may mostly likely be prohibited due to monitoring of a restricted diet, and pharmaceutical drug therapy is required.

Hypertension/beta blockers 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 (see Chapter 4). Therapy may include remedies with cardioprotective properties while the patient recovers normal blood pressure levels or regular life.

Nutrients: One or all • • • • • • • • • •

ALA Cod liver oil Coenzyme Q-10 Magnesium Herbal formulas: 1e3 Modified gambirplant branch formula Modified yang hyperactivity check with 7-drugs formula Modified liver subduing and wind stopping formula Modified blood pressure reducing decoction Modified qi replenishing and yin nourishing formula Modified cardiotonic formula

Hypertension/calcium channel blockers During this stage 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 normal blood pressure levels or regular life.

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Nutrients: One or all • • • • • • • • • •

ALA Cod liver oil Coenzyme Q-10 Chromium Magnesium Herbal formulas: 1e3 Modified yang hyperactivity check with 7-drugs formula Modified liver subduing and wind stopping formula Modified blood pressure reducing decoction Modified qi replenishing and yin nourishing formula Modified cardiotonic formula

Diuretics During the acute stage, patients should understand their body constitution, meal times, fluid intake, and proper elimination. Patients may experience improvement as the temporary symptoms associated with edema and fluid retention improve back to normal. This stage is also when patients experience a stressor or the effects of an illness that raises the blood pressure, causes exhaustion physical strain, breathing difficulty, and lower body edema. Therapy may include remedies with cardioprotective properties while the patient recovers normal blood pressure levels or regular life. Nutrients: One or all • Potassium • Magnesium • Vitamin C Herbal formulas: • Modified wu ling san • Modified huang ji huang qi wan

Lipidemia/statins 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. Supplementing with omega 3, niacin, and extra vitamin B3

Chapter 7 Treating according to disease stages

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

Positive inotropes 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 Blood pressure 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 increase in intraocular pressure and glaucoma. Areas of the eyes of concern include the retina, choroid, and the optic nerve. • Angiotensin-converting enzyme inhibitors (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 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 becoming increasingly resistant with potassium depletion or despite potassium and bicarbonate levels being within range, certain drugs may be indicated.

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• Hydrochlorothiazide or furosemide in combination with either spironolactone or amiloride corrects hypokalemia and normalizes the blood pressure. • A vasodilator or a beta blocker can be used 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.

Arrhythmia This stage is for patients experiencing mild symptoms who 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 • Potassium • Vitamin B12, used to relax mood and help build blood • 5-HTP, used to relax mood and reduce brain zaps with B12 Herbal formulas: 1e3 • An xin ning xin formula

Chapter 7 Treating according to disease stages

• • • • • • • • •

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

Common symptoms associated with taking common antiarrhythmic agents Adenosine Symptoms that resolve quickly without additional treatment: • Chest pressure • Headache and light-headiness • Dyspnea • Skin flushing ECG • Transient asystole, the treatment goal • A developing bradycardia, atrioventricular (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 include 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

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• • • • • • • • • • • • • • •

Other symptoms of pulmonary toxicity include: 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 part of popular drug for male sexual virility. It is also prescribed for hyperthyroid and other expanded uses. It is known to 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 include: • Shortness of breath • Coughing • Crackles and rales without clubbing

Chapter 7 Treating according to disease stages

• Hepatoxicity: jaundice ECG: • Prolonged QTc interval and hypotension

Disopyramide This drug causes ventricular problems, 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

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

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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, which 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 • 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

Chapter 7 Treating according to disease stages

characterized by Raynauds phenomenon, skin rash, vasculitis, and arthralgia arthralgias. 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 • 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, which are dose dependent. Clinical presentations include: Heart failure: • Dyspnea and breathlessness • Edema • 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

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Quinidine This drug acts on the potassium channels and may drug-induced 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 • Nausea with mild diarrhea and vomiting ECG • Cardiotoxicity: prolonged QTc interval • Ventricular arrhythmias

Antithrombotics During the chronic stages of coronary artery disease (CAD) condition this 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

Chapter 7 Treating according to disease stages

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.

Atherosclerotics Patients at risk of 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; 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.

Antiglycemics The general role of TCM and nutrients when initiated during acute or chronic stages is to help control and regulate blood sugar, excess lipid accumulation, and metabolism; and to fortify blood and energy levels. Complicated combinations of herbal formulas and nutritional supplementation can be used either in therapeutic concentrations for oral and topical use, or in weaker concentration for culinary use to enhance dietary practices. During the acute stage, patients should understand their body constitution and proper timing. They should know how to predict peak action of insulin and be guided about when snacks, meals, herbs, and nutritional supplements alone or integrated with oral and injected pharmaceutical drugs are indicated. Further, symptoms that hinder sexual recreation and procreation such as vaginal dryness, erectile dysfunction, and menstrual problems could experience improvement as the symptoms associated with hyperglycemia improve back to normal. During chronic stages that confirm diabetes diagnosis, patients can present with at least two other common occurrences concerning glycemic levels. The first is diabetic dermopathy.

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This condition involves the skin, and complaints range from itchiness, flakiness, and acanthosis nigricans of the neck, back arm pits, elbows, knuckles, and knees to hemorrhage and erosion ulcers that are often complicated by fungal and bacterial infections. The second is hypoglycemia. This happens in patients who are using injected or oral insulin and can occur in patients with diabetes for a variety of reasons including insulin resistance and lack of insulin production. Treatment strategy must include the type and stage of the diabetes and body constitution. Patients should understand proper timing, such as how to predict peak action of insulin when indicated snacks, meals, herbs, and nutritional supplements can be integrated with oral or injected pharmaceutical drugs. Patients with chronic and confirmed diabetes type 1 and 2 frequently monitor for several complications including DKA. DKA is preventable but when it does occur symptoms are typically dehydration with elevated glucose levels. They are hospitalized to rehydrate, restore electrolytes, and bring elevated glucose levels under control and stabilized. For patients with uncontrollable diabetes, those who are noncompliant, with DKA or kidney disease, herbs and nutrients may mostly likely be prohibited due to monitoring of a restricted diet, and pharmaceutical drug therapy is required.

Hypertension Most patients at risk of life-threatening symptoms associated with heart failure 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 are likely being monitored using complicated combinations of pharmaceutical drugs and hospital visits resulting in surgical intervention. Any positive effect that lifestyle changes, nutritional constituents, and many herbal formulations generally have would not provide much or any therapeutic benefit. For certain patients diagnostic testing results may not present physical changes in the heart and vessels, yet symptoms may be pointing to heart failure medication such as in preserved ejection fraction results and other testing that may suggest other causes of heart failure symptoms. If lifestyle changes can reduce the health risk and improve or maintain quality of life for the duration, then such changes must be implemented immediately on a regimen with intervals to note progress. These patients may become indicated for the benefits of nutritional supplements and herbal medicines integrated with pharmaceutical drugs with very close

Chapter 7 Treating according to disease stages

observation. The herbal medicines would need careful choosing of herbs and formulated not to negatively interact with drug therapy. Two major syndromes the patient may benefit noticeably are hypertension and anemia. See Chapters 4e6. Beta blockers may be used as an alternative drug for ACEIs when the patient has diagnosed diabetes or heart failure. They are not first-line agents for the treatment of hypertension and may be restricted for patients with respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) and angina and myocardial infarction. When weaning off of this drug to taper and possibly introduce herbal therapy and nutrition benefit, the doses should be gradually reduced over several weeks. Nutrients and herbal formulas produce similar but weaker dynamic effects as pharmaceutical beta blockers. They can be effective in many indicated patients, but must be reduced or eliminated completely if the blood pressure has sustained increases, with trending patterns that assume to threaten life or affect 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, the kidneys, and debilitating the patient toward heart failure.

Hypertension/beta blockers Beta blockers may be used as an alternative drug for ACEIs when the patient has diagnosed diabetes or heart failure. They are not first-line agents for the treatment of hypertension and may be restricted for patients with respiratory disorders such as asthma and COPD and angina and myocardial infarction. When weaning off of this drug to taper and possibly introduce herbal therapy and nutrition benefit, the doses should be gradually reduced over several weeks. Nutrients and herbal formulas produce similar but weaker dynamic effects as pharmaceutical beta blockers. They can be effective in many indicated patients, but must be reduced or eliminated completely if the blood pressure has sustained increases, with trending patterns that assume to threaten life or affect 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, the kidneys, and debilitating the patient toward heart failure.

Hypertension/calcium channel blocker Remedies from the acute stage can be effective and must be reduced or eliminated if the blood pressure has sustained

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increases, with trending patterns that assume to threaten life or affect 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 overall well-being is threatened because of elevated blood pressure, paroxysmal hypertension, palpitations, headache, pallor, and perspiration, the physician may be concerned 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 becoming increasingly resistant, with potassium depletion or despite potassium and bicarbonate levels being within range, certain drugs may be indicated. • 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. • Calcium antagonists have a glomerular vasodilatory effect, are effective in renal artery stenosis, and do not compromise renal function.

Diuretics See Chapter 10.

Lipidemia/statin 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 include: • Atorvastatin and amlodipine • Atorvastatin and ezetimibe • Lovastatin and niacin (nicotinic acid) • Simvastatin and ezetimibe • Simvastatin and niacin

Chapter 7 Treating according to disease stages

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 • 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, which causes 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 the weaning stage, before planning and managing treatment: • Modified zhi gan cao decoction • Modified shen fu decoction • Modified gui pi decoction

Lipidemia/statins • Yue jian cao you jiao wan

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• • • •

Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling Xi huang wan

Positive inotropes 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 • 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

Chapter 7 Treating according to disease stages

• 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: 1. Patients who are not candidates for advanced heart replacement therapy, for whom intravenous inotropes may also be considered as palliation at the end of life • Patients who are experiencing angina or rhythm disturbances who 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, which would provide a better therapeutic outcome than medications

Recovery stage Blood pressure 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 high risk 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 alcohol; those with African ancestry; and physical inactivity.

Antithrombotics Patients who visit a practitioner of TCM usually are looking for solutions to help with male virility, leg swelling, back pain, and overall energy. Practitioners may find, among other therapeutic

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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.

Atherosclerotics 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.

Antiglycemics The general role of TCM and nutrients when initiated during recovery and prevention stages is to help the body utilize and regulate normal use of glucose in the blood, normal lipid accumulation and metabolism, and sufficient blood content and levels. Single or simple herb combinations and nutritional supplementation can be used in daily health tonics, short-term regimens, and in culinary use to enhance dietary practices. During the recovery and prevention stages patients should become literate and proactive. Factors that affect glucose levels and initiate or cause its sustained elevation and recurrent symptoms can lead to future confirmed diabetes diagnosis. Understanding of the body constitution and proper timing is important. Patients must be educated on how to predict peak action of insulin and other symptoms and be guided about how to create a lifestyle to remain literate and proactive. During the recovery stages patients may be monitored through tapering down of prescribed pharmaceutical drugs. It is important to educate them about properly utilizing food and medicine. They should be educated about snacks and meals and when and how to integrate single or simple herb combinations and nutritional supplements with oral or injected pharmaceutical drugs.

Chapter 7 Treating according to disease stages

Hypertension/calcium channel blockers During the recovery stage, when a patient is weaning off of calcium channel blocker (CCB) drug therapy to herbal formulas for hypertension, patients often adopt a lifestyle that improves health. Food and nutritional choices in the diet must exclude pomelo and grapefruit whole or in juices. These products interfere with the pharmacodynamics of the medication, potentially causing harm due to accumulation of unmetabolized drug within the body. It is advised to give a time window of at least 4 h between consuming grapefruit and ingesting CCBs. 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%. Herbal formulas: 1e3 • Modified gambirplant branch formula • Modified yang hyperactivity check with 7-drugs formula • Modified liver subduing and wind stopping formula • Modified blood pressure reducing decoction • Modified qi replenishing and yin nourishing formula • Modified cardiotonic formula

Diuretics The general role of TCM and nutrients when initiated during recovery and prevention stages is to help the body utilize fluid intake and eliminate excess to maintain balance. Single or simple herb combinations and nutritional supplementation can be used in daily health tonics, short-term regimens, and in culinary use to enhance dietary practices. Nutrients: One or all • Potassium • Magnesium • Vitamin C Herbal formulas • Modified wu ling san • Modified huang ji huang qi wan

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Recovery stage Some patients may need to live on a fluid restriction, including drinks and food, of a minimum of 1 L up to a maximum of 2 L daily. Some patients may need to live on a salt restriction to assist with the desire to drink more fluids.

Symptoms that require emergency assistance Respiratory concerns: • Dyspnea during activity, at rest and while asleep • Wheezing • Difficulty breathing • Persistent cough that is either dry and hacking or blood-tinged expectoration Fluid metabolism: • Swelling in the legs, ankles, or feet • Profuse urination or increased frequency resulting in fully voiding the bladder, especially at night • Sudden and considerable weight gain or loss • Symptoms connected to medication side effects Cardiac concerns: • Pulse is slow or rapid • Heartbeat is distinctly felt in the chest and sensation is pounding and irregular or steady • Feeling tired or weak with a high pulse rate

Heart failure nitrates Clinical management of advancing heart failure with coronary artery disease and metabolic syndrome as causative factors involves disease surveillance, balancing health factors within subjective yet acceptable ranges. Therapies utilizing aggressive pharmacological and nonpharmacological therapies are for maintaining: • Blood levels: confirmed chronic anemia • Blood sugar: confirmed diabetes • Blood lipids: confirmed LDL, HDL, and cholesterols at unacceptably high or low levels • Blood pressure: confirmed hypertension

Pharmacological therapy Patients at the chronic stage and taking nitrates for confirmed diagnoses will have a prior history of serious noncompliance. They

Chapter 7 Treating according to disease stages

may likely not be indicated for Chinese herbal medicine and nutritional supplements, especially vitamin C and cysteine. The effectiveness is still subjective to findings in lab studies, disease stage, body constitution, and overall prognosis. None will have satisfactory clinical effects of much significance over the long term because concentric remodeling in confirmed and advancing diseases states do not present reversal. Pharmacodynamics of nitrates can increase blood pressure and the likelihood of anginal chest pains and emergency events, if interacted with other ingested pharmaceutical drug or Chinese herbal medications. Men are especially affected by certain blood pressure medications, with side effects that enhance experiences during sexual encounters, and can experience excessively dangerous drops in blood pressure that can be fatal. Common findings during therapy that often complicate care or have poor prognosis with resulting palliation: • Left main coronary artery stenosis >50% • Left ventricular dysfunction affecting the mitral valve and blood movement to through aorta to the rest of the body • Confirmed diabetes • Patients continue severe symptoms despite maximum medical therapy • Atherosclerotic lesions in left coronary artery and left ascending artery are conditions that are unstable and beyond benefit of percutaneous intervention • Unstable angina developing • Baseline epicardial adipose tissue thickness (EAT) ¼> 7 mm revealed during a revascularization procedure is a predictor of future unstable angina, myocardial infarction necessitating revascularizations, and sudden death

Nitrates 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

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• 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 • Persistent headache • Skin rash, including hives When weaning from nitrates to a modified lifestyle may involve the use of other medications. When indicated, alternate Chinese medicine formula(s) to recover after illness with pharmaceutical drugs. Administer within 3 h 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 TCM formula that recovers after illness and within 2 weeks after weaning from nitrates and pharmaceutical drugs, and 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 TCM formula that recovers after illness while monitoring vitals such as blood sugar, cholesterol, and blood pressure. 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

Chapter 7 Treating according to disease stages

• Modified mu xiao jiu xin wan • Modified dan shen yin

Positive inotropes 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. Use caution with modifying formulas with herbs 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 Blood pressure 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: 1e3 • Modified gambirplant branch formula • Modified yang hyperactivity check with 7-drugs formula • Modified liver subduing and wind stopping formula

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• Modified blood pressure reducing decoction • Modified qi replenishing and yin nourishing formula • Modified cardiotonic formula

Antithrombotics Patients who visit a practitioner of TCM 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.

Atherosclerotics 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.

Hypertension/calcium channel blockers In the western medicine community in the United States, certain groups are considered high-risk 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 alcohol; those with 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

Chapter 7 Treating according to disease stages

• 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: • Modified liver subduing and wind stopping formula • Modified qi replenishing and yin nourishing formula

Diuretics Patients should monitor weight daily before meals. Concern is for weight gain or loss of more than 3 lb daily or 5 lb weekly. • Potassium • Magnesium • Vitamin C

Nitrates 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 hormone levels regularly and adjust needs according to milestones at middle age such as menopause and andropause. • Check complete blood count at regular levels, especially for early detection of anemia and lipid levels. • Check blood sugar daily. • Check blood pressure daily. • 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.

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• • • • • •

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

Lipidemia/statins • • • • •

Yue jian cao you jiao wan Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling Xi huang wan

Further Reading Conte MS, Desai TA, Wu B, Schaller M, Werlin E. Pro-resolving lipid mediators in vascular disease. J Clin Invest. 2018;128(9):3727e3735. https://doi.org/ 10.1172/JCI97947. Copes F, Pien N, Van Vlierberghe S, Boccafoschi F, Mantovani D. Collagen-based tissue engineering strategies for vascular medicine. Front Bioeng Biotechnol. 2019;7:166. https://doi.org/10.3389/fbioe.2019.00166. Published 2019 Jul 12. Kambic T, Novakovic M, Tomazin K, Strojnik V, Jug B. Blood flow restriction resistance exercise improves muscle strength and hemodynamics, but not vascular function in coronary artery disease patients: a pilot randomized controlled trial. Front Physiol. 2019;10:656. https://doi.org/10.3389/ fphys.2019.00656. Published 2019 Jun 12. Wu W, Shan Z, Wang R, et al. Overexpression of miR-223 inhibits foam cell formation by inducing autophagy in vascular smooth muscle cells. Am J Transl Res. 2019;11(7):4326e4336. Published 2019 Jul 15. Yang M, Lao L. Emerging applications of metabolomics in traditional Chinese medicine treating hypertension: biomarkers, pathways and more. Front Pharmacol. 2019;10:158. https://doi.org/10.3389/fphar.2019.00158. Published 2019 Mar 8. Zeng L, Tang G, Wang J, et al. Safety and efficacy of herbal medicine for acute intracerebral hemorrhage (CRRICH): a multicentre randomised controlled trial. BMJ Open. 2019;9(5):e024932. https://doi.org/10.1136/bmjopen-2018024932. Published 2019 May 9. Zhu Y, Qu J, He L, et al. Calcium in vascular smooth muscle cell elasticity and adhesion: novel insights into the mechanism of action. Front Physiol. 2019; 10:852. https://doi.org/10.3389/fphys.2019.00852. Published 2019 Aug 7.

8 Lipoprotein, hypertension, and diabetes Chapter Objectives 1. Introduce lipoprotein disorders and the traditional Chinese medicine formulas, nutritional supplements, and pharmaceutical drugs used in treatment during the acute, chronic, recovery, and prevention stages. 2. Introduce hypertension and the traditional Chinese medicine formulas, nutritional supplements, and pharmaceutical drugs used in treatment during the acute, chronic, recovery, and prevention stages. 3. Introduce diabetes and the traditional Chinese medicine formulas, nutritional supplements, and pharmaceutical drugs used in treatment during the acute, chronic, recovery, and prevention stages.

Lipoprotein disorders Apolipoprotein B (apoB) are nonexchangeable lipoproteins in two forms in humans, apoB-100 and apoB-48. They are responsible for the transport of lipids and cholesterol and can be used as a genetic marker that predisposes a patient for dangerously high LDL leading to cardiovascular disorders later in life. High Lp(a) (lipoprotein a) levels are mostly seen in patients with high LDL levels, and may be a biomarker of lipoprotein disorders in patients with chronic kidney disease and/or coronary artery disease. Lp(a) is not recommended to be used alone as a sole test for determining cardiovascular risk, but rather as an additional measure to be combined with assessment of traditional cardiovascular risk factors. The measurement of Lp(a) may be most useful in intermediate-risk patients or in those for whom the test result would affect treatment or the aggressiveness of treatment of known cardiovascular risk factors. Clinical pearls • Reference ranges of Lp(a) vary according to assay and reporting laboratories. • Lp(a) ranges differ according to different groups of people around the world. • Lp(a) level 10 mg/ dL ¼ increase in cardiovascular risk. Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00008-4 Copyright © 2020 Elsevier Inc. All rights reserved.

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Current medications Traditional Chinese medicine 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

Traditional Chinese medicine formulas for arrhythmia Herbal medicine

Action

Yue jian cao you jiao wan Bao jian mei jian fei cha Pu ji xiao du yin wan Gan mao ling Xi huang wan

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

Zhi gan cao decoction Shen fu decoction Gui pi decoction

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 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

Chapter 8 Lipoprotein, hypertension, and 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 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 (CAD) 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

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

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

Prescription plant sterols These drugs are 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 Aspirin These drugs are blood thinners, which prevent blood from forming atheromas and other clots. Clopidogrel This drug is used to prevent clots from forming inside of artery stents. Ticagrelor Prasugrel These drugs are used to prevent clots from forming inside of artery stents and 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.

Chapter 8 Lipoprotein, hypertension, and diabetes

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.

Angiotensin-converting enzyme inhibitors These drugs are used in patients with hypertension, chronic kidney disease, and proteinuria. They suppress the renin-angiotensinaldosterone system by preventing the conversion of angiotensin I to angiotensin II and blocking the major pathway of the degradation of bradykinin by inhibiting angiotensin-converting 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 II induced vasoconstriction, reduce sodium retention, and reduce aldosterone release. Angiotensin receptor blockers (ARBs) are used alone or often combined with a diuretic.

Beta blockers 1. Beta-1 receptor blockers 2. Alpha-1 receptor blockers 3. Intrinsic sympathomimetic

Beta-1 receptor blockers These drugs block beta-1 receptors and act selectively, yet can act nonselectively if given at higher doses. When weaning off of this drug, the doses should be gradually reduced over several weeks.

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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 of 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.

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.

Hypertension Hypertension presents as primary or secondary. Primary causes are due to congenital or environmental factors. Secondary causes are related to renal, vascular, and endocrine disease. The progression of essential hypertension is as follows: 1. Prehypertension in persons aged 10e30 years (by increased cardiac output)

Chapter 8 Lipoprotein, hypertension, and diabetes

2. Early hypertension in persons aged 20e40 years (in which increased peripheral resistance is prominent) 3. Established hypertension in persons aged 30e50 years 4. Complicated hypertension in persons aged 40e60 years

Primary hypertension: environmental and genetic causes Environmental factors of life and psychosocial stressors affect cortisol reactivity, an index of hypothalamic-pituitary-adrenal function. Mental stress induces a DNA methylase, which enhances autonomic responsiveness. Obesity, diabetes, and heart disease have genetic (genomewide association studies) contributions with multiple loci and are linked to hypertension. Multiple gene loci in known pathways of hypertension are immune-related. • DNA methylation and histone modification develop in the nephrons and are caused by a high-salt diet. • In pregnant women, the pattern of serine protease inhibitor gene methylation predicts preeclampsia. • During gestation (in vivo), maternal water deprivation and protein restriction during pregnancy leads to increases in renin-angiotensin expression in the developing fetus. • T lymphocytes and T-cell derived cytokines activation and filtration problems in the kidneys and vessels result in persistent, sustaining, and worsening hypertension with end organ damage.

Secondary hypertension: renal system failures Renal causes of hypertension include the renal parenchymal diseases and renal vascular diseases, as follows: • Chronic kidney disease • Polycystic kidney disease • Renin-producing tumor • Urinary tract obstruction

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JNC 7 classification and recommendations to lower blood pressure

JNC 7 Classification of blood pressure for adults aged 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

Weight loss Limit alcohol intake to a range of 15e30 mL/day Reduce sodium intake to no more than 100 mmol/day Maintain adequate intake of dietary potassium (approximately 90 mmol/day) Maintain adequate intake of dietary calcium and magnesium for general health Stop smoking Reduce intake of dietary saturated fat and cholesterol Aerobic exercise at least 30 min/day

Management Congestive heart failure occurs 2e4 times greater in patients with diabetes than in patients without. Control of hypertension in western medicine includes enteric coated aspirin (80e100 mg), but clopidogrel with aspirin intolerance. This is intended to reduce cardiovascular risk in patients with a glomerular filtration rate (GFR) of 60e89 mL/min only but may not be effective to prevent atherosclerosis or subsequent events in patients taking oral hypoglycemic agents or insulin. Patients with diabetes who are at high risk for cardiovascular events receive statin therapy to help lower LDL cholesterol levels. However, statin therapy may cause increased risk of developing diabetes. The following can be included in moderation for management of hypertension: • Low in sodium and high in potassium food • Consuming a variety of fruits and vegetables • Low-fat meat and dairy products • Moderate physical activity of 30 min or more daily for fitness and weight maintenance/loss

Chapter 8 Lipoprotein, hypertension, and diabetes

Evaluation studies to determine organ nephrological causes of hypertension: • Complete blood count and routine lab studies • Uric acid • Urine microalbumin • Blood glucose or A1c • Serum sodium • Serum potassium • Creatinine • LDL, HDL, and triglycerides • Chest radiography • Physical examination, which includes special positions in blood pressure measurements • 12-lead electrocardiogram Laboratory Studies of Secondary Causes of Hypertension

Cause

Diagnostic test

Chronic kidney disease Coarctation of the aorta Cushing syndrome with steroidal use Illicit drug-induced Pheochromocytoma Primary aldosteronism/ mineralocorticoid excess

Estimated glomerular filtration rate Computed tomography angiography Dexamethasone suppression test

Renovascular hypertension

Sleep apnea

Thyroid/parathyroid disease

Drug screening for marijuana, cocaine, etc. 24-hour urinary metanephrine and normetanephrine • Plasma aldosterone-to-renin activity ratio • 24-hour urinary aldosterone level • Saline infusion to determine aldosterone level suppression • Mineralocorticoid tests • Doppler flow ultrasonography • MRI • Computed tomography angiography • Epworth sleepiness scale • Sleep study with oxygen saturation including determination and count of snoring and breathing cessation period during sleep Thyroid stimulating hormone level, serum parathyroid hormone level

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Current medications These medicines are suggested in western medicine: • Heart failure: Thiazide, beta blocker, angiotensin converting enzyme inhibitor (ACEI), ARB • Diabetes: ACEI • Chronic kidney disease (CKD): ACEI, ARB • Postmyocardial infarction: Beta blocker, ACEI

Traditional Chinese medicine

Traditional Chinese medicine formulas for hypertension Herbal medicine

Action

Modified gambirplant branch formula Modified yang hyperactivity check with 7drugs 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

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)

Chapter 8 Lipoprotein, hypertension, and diabetes

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

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

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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

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

Chapter 8 Lipoprotein, hypertension, and diabetes

veins. Side effects include dizziness, headache, and drowsiness, in addition to orthostatic and first-dose hypotension.

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 ACE. They are often considered strong when used alone, without a diuretic, but can be combined with one.

Angiotensin receptor blockers Angiotensin-2 Receptor Antagonists These drugs are primarily used when a patient is unable to tolerate ACEIs. They block the binding of angiotensin II to angiotensin type I receptors, reduce effects of angiotensin II induced vasoconstriction, reduce sodium retention, and reduce aldosterone release. ARBs are used alone or often are combined with a diuretic.

Beta blockers 1. Beta-1 receptor blockers 2. Alpha-1 receptor blockers 3. Intrinsic sympathomimetic Beta-1 receptor blockers These drugs block beta-1 receptors, act selectively, yet can act nonselectively if given at higher doses. When weaning off of this drug, the doses should be gradually reduced over several weeks.

Calcium channel blockers These drugs limit the amount or rate of calcium allowed into heart muscle and arteries so that those tissues will relax, which lowers blood pressure. They are generally used to treat hypertension, arrhythmia, and angina. They 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, patients with diabetes including kidney

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disease, and the elderly. Other medicines often taken with calcium antagonists for hypertension are ACEIs, ARBs, and diuretics.

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 work 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.

Renin inhibitors These drugs act within the renin-angiotensin system, a hormone system 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 raise the blood pressure, fluctuating between stage 1 and 2. Therapy may include remedies with cardioprotective

Chapter 8 Lipoprotein, hypertension, and diabetes

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: 1e3 • Modified yang hyperactivity check with 7-drugs formula • Modified liver subduing and wind stopping formula • Modified blood pressure 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 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 increasingly becomes 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.

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• 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 that may be due to medication can manifest: • 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 high risk, 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 alcohol; those with 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

Chapter 8 Lipoprotein, hypertension, and diabetes

• • • • • • • •

Coenzyme Q-10 Chromium Magnesium Potassium Selenium Vitamin B6 and folic acid Vanadium Zinc

Herbal formulas: 1e3 • • • • • •

Modified Modified Modified Modified Modified Modified

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

Clinical pearls • Neurologic: hypertensive encephalopathy, cerebral vascular accident/cerebral infarction, subarachnoid hemorrhage, intracranial hemorrhage • Cardiovascular: myocardial ischemia/infarction, acute left ventricular dysfunction, acute pulmonary edema, aortic dissection, unstable angina pectoris • Other: acute renal failure/insufficiency, retinopathy, eclampsia, microangiopathic hemolytic anemia The natural history of essential hypertension evolves from occasional to established hypertension. After a long invariable asymptomatic period, persistent hypertension develops into complicated hypertension, in which end-organ damage to the aorta and small arteries, heart, kidneys, retina, and central nervous system is evident.

Diabetes A population of patients who don’t have type 1 diabetes but develop type 2 diabetes could have a genetic as well as an environmental/lifestyle cause. The genetic component is the transcription factor 7elike 2 (TCF7L2). TCF7L2 and specific variants

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have been associated with 1.5- fold in heterozygotes and 2.4- fold in homozygotes in South American, Central American, and African American patients.

Prediabetes This condition precedes type 2 diabetes, is characterized by a fasting blood glucose level of 100e125 mg/dL or a two-hour post-oral glucose tolerance test (post-OGTT) glucose level of 140e200 mg/dL. Patients are at increased risk for vascular diseases and developing type 2 diabetes. It can be prevented and managed alone by a patient. A primary care physician should continually assess vitals and progress. When a patient can no longer maintain normal glycemic, lipid, or blood pressure control they need to visit a diabetes specialist immediately because advanced complications are very difficult or impossible to reverse. Metabolic syndrome/syndrome X/insulin-resistance can occur in patients with normal glucose levels. Fasting insulin levels are generally increased at an earlier stage, but they are more directly related to insulin clearance than to insulin resistance. Diagnosis can be confirmed when a patient has at least three of the following five conditions: • Abdominal obesity • Blood pressure elevated and sustained • Elevated triglyceride level • Low level of high-density lipoprotein (HDL) cholesterol • Fasting glucose value of 100 mg/dL or higher

Type 2 diabetes and dawn phenomenon The dawn phenomenon commonly occurs in type 2 diabetic patients, in the early morning hours around or just before sunrise and is characterized as a blood glucose increase of over 20 mg/ dL. In some cases the blood sugar drops to near 40e50 mg/dL and the patient will show signs of confusion, body shaking, and inability to speak coherently. This patient would need skilled immediate care with protein- or sugar-laden drinks and snacks or would need transport to an emergency facility.

Management • • • • •

Ophthalmologic complications Lipid accumulation and CAD Diabetic neuropathy Infections Intercurrent medical illness

Chapter 8 Lipoprotein, hypertension, and diabetes

• Critical illness • Pharmacology and surgery elections • Stroke prevention

Glucose studies Oral Glucose Tolerance Test The oral glucose tolerance test (OGTT) measures the body’s ability to use glucose, which is the main source of energy for the body. This test can be used to diagnose prediabetes, gestational diabetes in pregnant mothers, and diabetes type 1 and 2. Fasting Plasma Glucose Fasting plasma glucose (FPG) is measured 8 h after the last meal. Normal range in individuals without diabetes is 70e100 mg/dL. • 91e99 mg/dL predicts future type 2 diabetes • 100e125 mg/dL is considered an impaired fasting glucose • HbA1c should also be included in a study of an asymptomatic, but suspected diabetic patient whose random serum glucose level >140 mg/dL • A random plasma glucose of 200 mg/dL or higher in a patient with hyperglycemic crisis or hyperglycemic symptoms of weight loss, polyuria, polydipsia, and polyphagia

HbA1c This is a common blood test used to diagnose and manage type 1 and type 2 diabetes. It measures the percentage of blood hemoglobin that includes sugar. It averages blood sugar level for the past 2e3 months. • This test should be considered an additional optional diagnostic criterion, rather than a primary criterion for diagnosis of diabetes. • Normal glucose tolerance range is 4%e5.7% in individuals without diabetes. • 6%e6.4% is neither normal glucose tolerance nor diabetes, and can indicate prediabetes. • > 6.4% is considered diagnostic for diabetes and should be redone and performed in a laboratory twice along with FPG, OGTT, and DCCT reference assay to confirm diabetes.

Current medications These medicines are suggested in western medicine: • Heart failure: Thiazide, beta blocker, ACEI, ARB • Diabetes: ACEI

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• CKD: ACEI, ARB • Postmyocardial infarction: Beta blocker, ACEI

Traditional Chinese medicine

Traditional Chinese medicine formulas for arrhythmia Herbal medicine

Action

Yu quan wan Zuo gui wan Liu wei di huang wan Zhi gan cao decoction Shen fu decoction Gui pi decoction

Nourishes kidney yin, clears heat Nourishes kidney yin, increases jing Nourishes kidney and liver yin, increases jing 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; helps reduce neuropathy pain Caution: May lower blood sugar too much; avoid in pregnancy and nursing Berberine Benefits: Reduces excess blood sugar, alleviates neuropathy pain, and improves insulin utilization Caution: May cause gastrointestinal problems with high doses Chromium Benefits: Production, storage, and secretion of insulin; blood sugar diffuses into cells Caution: Long-term use may cause kidney issues in patients with diabetes. Magnesium Nutritional constituents: Citrate, stearate, and sulfate forms

Chapter 8 Lipoprotein, hypertension, and diabetes

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 Melatonin Nutritional constituents: Fruits and vegetables Benefits: Indirectly helps with inducing sleep, which assists with insulin production and glucose reduction Caution: May raise glucose levels in some patients Omega-3 fatty acids Nutritional constituents: Vitamins A, D, fish oils, flax seed, primrose, borage, and flaxseed oils Benefits: Lowers triglycerides, raises HDL, may not affect blood glucose or total cholesterol Caution: May raise LDL, may interfere with warfarin and blood pressure medicines Probiotics Nutritional constituents: Lactobacillus, bifidobacterium Benefits: Lowers glucose levels and insulin Caution: May cause bloating Vanadium Benefits: Production, storage, and secretion of insulin; blood sugar diffuses into cells Caution: Long-term use may cause kidney issues in patients with diabetes. Vitamin B-1 Nutritional constituents: Thiamine (water soluble), benfotiamine (lipid soluble) Benefits: Blood vessels, blood sugar, heart functioning Vitamin D Nutritional constituents: Vitamins A, D, fish oils, flax seed, primrose, borage, and flaxseed oils Benefits: Insulin function, heart function, kidney function

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Pharmaceutical drugs Oral and injectable insulin drugs For all diabetics, controlling the disease involves utilization of insulin. Patients with type 2 diabetes are often prescribed two classes of oral hypoglycemic agents (OHAs) because they face not producing enough insulin and need to increase insulin output, and they also have insulin resistance and need to improve how their body distributes and utilizes insulin. Insulin output increasers These drugs help with secretion of insulin in the beta cells of the islets of Langerhans in the pancreas. These drugs commonly lose effectiveness during long-term use. Side effects include hypoglycemia and weight gain. Sulfonylurea group These drugs have a relative slow release and distribution within the body. Nonsulfonylurea Group These drugs cause weight gain but responds faster and with shorter duration than the sulfonyl group. Dipeptidyl Peptidase-4 Inhibitors These drugs have a weaker effect than the sulfonylurea and nonsulfonylurea groups, but less frequently cause hypoglycemia and weight gain. Alpha-glucosidase inhibitors These drugs have the weakest effect on the control of diabetes, but reduce absorption of glucose in the small intestine, though the side effects are gastrointestinal problems including nausea and diarrhea. Glucose output and uptake reducers These drugs decrease glucose production and accumulation in the liver and increase sensitivity and utilization of glucose in the muscle cell. They do not cause the weight gain and hypoglycemia like OHA drugs. The disadvantages are vitamin B12 blocking, which inhibits red blood cell production, and gastrointestinal symptoms of nausea and bowel disturbances. • Metformin

Chapter 8 Lipoprotein, hypertension, and diabetes

Insulin resistance reducers These drugs have a weaker effect than Metformin but still decrease glucose production and accumulation in the liver and increase sensitivity. The emphasis is to increase utilization of glucose in the muscle cell. • Thiazolidinediones • Glitazones Noninsulin injected drugs These drugs are often prescribed in conjunction with OHAs to stimulate insulin secretion, reduce glucose production, yet enhance utilization, reducing excessive weight gain by helping with appetite control, and prolonging stomach emptying time and reducing side effects that affect the cardiovascular system. • Glucagon-like peptide analogues: given once weekly instead of traditional twice daily • Pramlintide acetate • SGLT2 inhibitors: inhibit kidney glucose reabsorption • Incretin • Glucokinase activators

Acute and chronic stages The general role of traditional Chinese medicine and nutrients when initiated during acute or chronic stages is to help control and regulate blood sugar, excess lipid accumulation, and metabolism; and to fortify blood and energy levels. Complicated combinations of herbal formulas and nutritional supplementation can be used either in therapeutic concentrations for oral and topical use or in weaker concentration for culinary use to enhance dietary practices. During the acute stage, patients should understand their body constitution and proper timing. They should know how to predict peak action of insulin and be guided about when snacks, meals, herbs, and nutritional supplements alone or integrated with oral and injected pharmaceutical drugs are indicated. Further, symptoms that hinder sexual recreation and procreation such as vaginal dryness, erectile dysfunction, and menstrual problems could experience improvement as the symptoms associated with hyperglycemia return to normal. During chronic stages that confirm diabetes diagnosis, patients can present with at least two other common occurrences concerning glycemic levels. The first is diabetic dermopathy. This condition involves the skin, and complaints range from

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itchiness, flakiness, and acanthosis nigricans of the neck, back arm pits, elbows, knuckles, and knees to hemorrhage and erosion ulcers that are often complicated by fungal and bacterial infections. The second is hypoglycemia. This happens in patients who are using injected or oral insulin and can occur in patients with diabetes for a variety of reasons including insulin resistance and lack of insulin production. Treatment strategy must include the type and stage of the diabetes and body constitution. Patients should understand proper timing, such as how to predict peak action of insulin when indicated; snacks, meals, herbs, and nutritional supplements can be integrated with oral or injected pharmaceutical drugs. Patients with chronic and confirmed diabetes type 1 and 2 frequently monitor for several complications including diabetic ketoacidosis (DKA). DKA is preventable but when it does occur symptoms are typically dehydration with elevated glucose levels. They are hospitalized to rehydrate, restore electrolytes, and bring elevated glucose levels under control and stabilized. For patients with uncontrollable diabetes, those who are noncompliant, with DKA or kidney disease, herbs and nutrients may mostly likely be prohibited due to monitoring a mandatory restricted diet, and pharmaceutical drug therapy is required.

Recovery and prevention stages The general role of traditional Chinese medicine and nutrients when initiated during recovery and prevention stages is to help the body utilize and regulate normal use of glucose in the blood, normal lipid accumulation and metabolism, and sufficient blood content and levels. Single or simple herb combinations and nutritional supplementation can be used in daily health tonics, shortterm regimens, and culinary use to enhance dietary practices. During the recovery and prevention stages patients should become literate and proactive. Factors that affect glucose levels and initiate or cause its sustained elevation and recurrent symptoms can lead to future confirmed diabetes diagnosis. Understanding body constitution and proper timing is important. Patients must be educated on how to predict peak action of insulin and other symptoms and be guided about how to create a lifestyle to remain literate and proactive. During the recovery stages patients may be monitored through tapering down of prescribed pharmaceutical drugs. It is important to educate them about properly utilizing food and medicine. They should be educated about snacks and meals and when and how to

Chapter 8 Lipoprotein, hypertension, and diabetes

integrate single or simple herb combinations and nutritional supplements with oral or injected pharmaceutical drugs. The prevention stage may be represented through two aspects: Prevention as a prophylaxis and a confirmed diabetes diagnosis with prevention of complication or recurrence of symptoms that point to advanced stages. As a prophylaxis for patients without diabetes or who had a recent acute stage experience due to medical or unknown reasons, snacks, meals, herbs, and nutritional supplements alone are sufficient. Common complications to prevent are DKA and kidney disease. In both cases patients should continue monitoring under the direct care of a physician, which includes continued oral and injected medication use and selective food, herb, and nutrient intake to avoid those that typically cause dangerous elevations of the blood sugar, blood pressure, ketone levels, cholesterol, and infections that will affect the kidneys.

Further Reading 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. Bosu WK, Aheto JMK, Zucchelli E, Reilly ST. Determinants of systemic hypertension in older adults in Africa: a systematic review. BMC Cardiovasc Disord. 2019;19(1):173. https://doi.org/10.1186/s12872-019-1147-7. Published 2019 Jul 22. Bosu WK, Reilly ST, Aheto JMK, Zucchelli E. Hypertension in older adults in Africa: a systematic review and meta-analysis. PLoS One. 2019;14(4):e0214934. https:// doi.org/10.1371/journal.pone.0214934. Published 2019 Apr 5. Chimberengwa PT, Naidoo M. A description of community-based participatory research of hypertension awareness, prevention and treatment in a district of Matabeleland South Province, Zimbabwe. Afr J Prim Health Care Fam Med. 2019;11(1):e1ee9. https://doi.org/10.4102/phcfm.v11i1.1839. Published 2019 Jan 31. Fisher NDL, Fera LE, Dunning JR, et al. Development of an entirely remote, nonphysician led hypertension management program. Clin Cardiol. 2019;42(2): 285e291. https://doi.org/10.1002/clc.23141. Geraci G, Buccheri D, Zanoli L, et al. Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease. Exp Ther Med. 2019;17(4):3255e3263. https:// doi.org/10.3892/etm.2019.7279. Harshfield EL, Koulman A, Ziemek D, et al. An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their association with coronary heart disease risk factors. J Proteome Res. 2019;18(6): 2397e2410. https://doi.org/10.1021/acs.jproteome.8b00786. Jung HJ, Kwon TH. New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus. Kidney Res Clin Pract. 2019;38(2):145e158. https://doi.org/ 10.23876/j.krcp.19.002.

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Kilpeläinen TO, Bentley AR, Noordam R, et al. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun. 2019;10(1):376. https://doi.org/10.1038/s41467-018-08008-w. Published 2019 Jan 22. Letourneau LR, Greeley SAW. Congenital diabetes: comprehensive genetic testing allows for improved diagnosis and treatment of diabetes and other associated features. Curr Diab Rep. 2018;18(7):46. https://doi.org/10.1007/ s11892-018-1016-2. Published 2018 Jun 13.  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. Sanyoura M, Philipson LH, Naylor R. Monogenic diabetes in children and adolescents: recognition and treatment options. Curr Diab Rep. 2018;18(8): 58. https://doi.org/10.1007/s11892-018-1024-2. Published 2018 Jun 22. Smedegaard SB, Jørgensen JO, Rittig N. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and subsequent central diabetes insipidus: a rare presentation of pituitary apoplexy. Case Rep Endocrinol. 2019;2019: 7592648. https://doi.org/10.1155/2019/7592648. Published 2019 Apr 2. 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.

9 Cardiac rhythm diseases Chapter Objectives 1. Introduce cardiac rhythm disease conditions as seen in integrative cardiovascular Chinese medicine 2. Understand background on types of heart blocks 3. Introduce traditional Chinese medicine formulas and their actions 4. Introduce nutritional supplements and their active constituents, benefits and cautions. 5. Introduce pharmaceutical drugs and their actions and pharmacogenetics. 6. Discuss therapies for the acute and chronic stages.

Most cardiomyopathies are inherited in an autosomal dominant pattern, except dystrophia myotonia and those associated with skeletal muscle disease, which are usually X-linked. Structural heart disease is a well-recognized risk factor for the occurrence of ventricular tachycardia.

Background on heart blocks Atrioventricular block Atrioventricular (AV) block is a type of arrhythmia that involves low cardiac output, hypotension, and end-organ hypoperfusion leading to sudden death. Symptoms can range from having no symptoms to exercise intolerance, fatigue, shortness of breath, weakness, or syncope. Treatment usually is a pacemaker. There is a greater risk of atrial fibrillation and a poorer prognosis than heart failure. Causes: • Ischemia • Bezold-Jarisch reflex: An inferior myocardial infarction, which may cause a temporary increase in vagal tone leading to transient Mobitz I or complete AV block • Degenerative changes • Infection seen in myocarditis Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00009-6 Copyright © 2020 Elsevier Inc. All rights reserved.

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• Infiltrative processes as seen in Lyme disease and sarcoidosis • Beta blockers and calcium antagonists that slow AV node activity • Procaniamide and flecainamides that block His-Purkinje conduction or lengthen AV node refractoriness Categorizations: • First-degree AV block • Conduction delay or slowing in AV node and His-Purkinje system • EKG: PR interval exceeds 0.20 s (sec) • Intrinsic disease of the AV node, high vagal tone, or dual AV nodal pathways (two separate PR intervals) • Beta blockers, calcium channel antagonists, digitalis, and select antiarrhythmic medications that prolong the PR interval • Second-degree AV block • Some P waves conduct while others do not • Mobitz I (Wenckebach) - Increased vagal tone - Degenerative disease of the AV conduction system, seen in elderly skilled nursing patients - AV nodeeblocking medications - Lyme disease, sarcoidosis, myocarditis • Mobitz II/2:1 block - Degenerative disease of the His-Purkinje system - Damage of the conduction system • Coronary artery disease • Infiltrative cardiomyopathies (sarcoidosis, hemochromatosis), myxedema, Lyme disease, neuromuscular disease • Myocardial infarction • Myocarditis • Systemic diseases (ankylosing spondylitis, Reiter syndrome) • Valve surgery • Third-degree/AV block • Anterior myocardial infarction causing ischemia or infarction of the bundle branches • Cardiac surgery, catheter ablation of the AV node, alcohol septal ablation, or neuromuscular disease • Reversible causes: AV nodeeblocking drugs and ischemia • Pathologic causes: - Cardiomyopathy (infiltrative, idiopathic, and infarction) - Myocarditis (Lyme disease) - Endocarditis - Hyperkalemia

Chapter 9 Cardiac rhythm diseases

Ventricular arrhythmias This is a group of congenital cardiac arrhythmias including the long QT syndrome (LQTS) and Brugada syndrome characterized with the cause of sudden cardiac death in a structurally normal heart. ECG findings include: • Prolonged PR interval • Right bundle branch block • ST-segment elevation and a negative T wave in leads V1 and V2 Other reasons influencing causes: • Drugs: antiarrhythmics, antimalarials, antidepressants • Fever • Hyperglycemia

Arrhythmogenic right ventricular dysplasia/ cardiomyopathy Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic cardiomyopathy characterized by structural and functional right ventricular (RV) abnormalities. The genetic mutation occurs on chromosome 17q21 and the genetic abnormalities are located on chromosomes 1, 2, 3, 6, 7, 10, 12, and 14. The responsible genes: • plakoglobin ( JUP) • desmoplakin (DSP) • plakophilin-2 (PKP2) • desmoglein-2 (DSG2) • desmocollin-2 (DSC2) • ryanodine receptor-2 (RYR2) • transmembrane protein 43 (TMEM43) Pathophysiology The structural abnormalities in ARVD result from the fatty infiltration and fibrosis of the RV myocardium. This leads to progressive RV dilatation and dysfunction. The left ventricle is less commonly involved, but when it is the prognosis is usually very poor. • Apoptosis (programmed cell death) • Inflammation, enhanced fibrosis, and loss of function • Fatty replacement of myocardium Diagnosing • Exercise stress testing: Exercise-induced ventricular tachycardia of left bundle branch block (LBBB) morphology may be detected with this method. • Twenty-four-hour Holter monitoring • Echocardiography • Right ventriculography

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• Electrophysiology testing • Genetic testing

Current medications/treatment AV block • • • • • • • • • • • • • • •

Atropine IV/IM Vasopressors, alpha/beta agonists Dopamine Dobutamine Exercise is not recommended in patients with third-degree AV block. Ventricular Arrhythmia Beta blockers Left stellectomy Pacemaker Implantable cardioverter-defibrillator ARVC/ARVD Flecainide Propafenone Sotalol Amiodarone Advised against participation in competitive sports Avoid cardiac stimulants such as caffeine/pseudoephedrine/ ma huang products

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

Traditional Chinese medicine formulas for arrhythmia Herbal medicine 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

Action 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

Chapter 9 Cardiac rhythm diseases

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 Coenzyme Q10 Benefits: Heart, muscle, liver, and lungs; improves glycemic index, myocardial energy. Caution: Body stores 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

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

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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.

Class I: Sodium channel blockers

Class IA agents

• • • • •

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

Chapter 9 Cardiac rhythm diseases

Class IB agents

Class IC agents

Class II: Betaadrenergic blockers Class III: Potassium channel blockers Class IV: Calcium channel blockers

• • • • • • • • • • • • • • •

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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; decreases 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; caution in renal failure

Procainamide Sodium and potassium channel blocker and prolong the action potential duration of ventricular myocytes and Purkinje fibers 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

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Metabolism: Hepatic elimination is 60%e80% and renal elimination is 20%e40%; 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 for this purpose and should not be taken with lidocaine). Metabolism: Hepatic metabolism by CYP3A4 into an active metabolite

Mexiletine Sodium channel blocker; leads to phase 0 depolarization reduction rate and shortens action duration of Purkinje fibers and prevents delayed ventricular repolarization and torsades de pointes in LQTS. • 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%; caution in hepatic and renal disease

Class IC antidysrhythmics Flecainide Sodium channel blocker has negative inotropic effects and slows conduction in all cardiac fibers • Indications: Paroxysmal atrial fibrillation and ventricular dysrhythmias, used to help diagnose and treat congenital Brugada and LQT3 syndromes • Metabolism: Hepatic metabolism CYP2D6 at 75% and renal metabolism at 25%; 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

Chapter 9 Cardiac rhythm diseases

Class III antidysrhythmics Amiodarone Sodium, L-type calcium potassium channel or beta receptor delayer or blocker; 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, caution in renal disease so creatinine clearance is necessary and excreted unchanged by kidneys

Class V antidysrhythmics Adenosine Induces a short-duration heart block and atrial action potential, polarizes myocyte membrane potential and slows AV node conduction, and increases potassium conduction Indications: Given for supraventricular tachycardias 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

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• 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; 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

Acute and chronic stages As already inferred in the Chapter 5 Background of arrhythmia, 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 for traditional Chinese medicine 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 of the medications and are experiencing adverse effects that they hope can be alleviated using natural remedies.

Chapter 9 Cardiac rhythm diseases

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 taking two weeks to wean off of medications without any trouble. Patients will present to the clinic for herbal medicines while weaning off of current medications. Their reasons are 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. These patients will open capsules to count out granules and titrate dosages over time, usually between 6 and 24 months of continued prescription filling. Under very close supervision, if it is indicated that patients taking SSRIs and MAOIs 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 traditional Chinese medicine and are currently taking prescription drugs that have serious side effects or toxicities, or patients who have overmedicated themselves in the attempt 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

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• 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, helping 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 B-6 • 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 • Potassium • Vitamin B12, used to relax mood and help build blood • 5-HTP, used to relax mood and reduce brain zaps with B12 Herbal Formulas 1e3

Chapter 9 Cardiac rhythm diseases

• • • • • • • • • •

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 Black N, D’Souza A, Wang Y, et al. Circadian rhythm of cardiac electrophysiology, arrhythmogenesis, and the underlying mechanisms. Heart Rhythm. 2019;16(2):298e307. https://doi.org/10.1016/j.hrthm.2018.08.026. Cronin EM, Bogun FM, Maury P, et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. J Arrhythm. 2019;35(3):323e484. https://doi.org/10.1002/joa3.12185. Published 2019 May 10. Jain A, Alam S, Viralam SK, Sharique T, Kapoor S. Incidence, risk factors, and outcome of cardiac arrhythmia postcardiac surgery in children. Heart Views. 2019;20(2):47e52. https://doi.org/10.4103/ HEARTVIEWS.HEARTVIEWS_88_18. Neo WL, Ng ACW, Rangabashyam M, et al. Prevalence of cardiac arrhythmias in Asian patients with obstructive sleep apnea: a singapore sleep center experience. J Clin Sleep Med. 2017;13(11):1265e1271. https://doi.org/ 10.5664/jcsm.6794. Published 2017 Nov 15. Shizukuda Y, Rosing DR. Iron overload and arrhythmias: Influence of confounding factors. J Arrhythm. 2019;35(4):575e583. https://doi.org/ 10.1002/joa3.12208. Published 2019 Jun 20.

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10 Chamber and valve diseases Chapter Objectives 1. Introduce chamber and valve diseases as seen in integrative cardiovascular Chinese medicine. 2. Introduce atrioventricular blocks. 3. Introduce ventricular arrhythmias. 4. Introduce cardiomyopathy. 5. Introduce valvular heart disease. 6. Introduce mitral valve prolapse. 7. Introduce traditional Chinese medicine formulas and their actions. 8. Introduce nutritional supplements and their active constituents, benefits, and cautions. 9. Introduce pharmaceutical drugs and their actions and pharmacogenetics. 10. Discuss therapies for the acute and chronic stages.

Atrioventricular block See Chapter 9.

Ventricular arrhythmias See Chapter 9.

Arrhythmogenic right ventricular dysplasia/ cardiomyopathy See Chapter 9.

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00010-2 Copyright © 2020 Elsevier Inc. All rights reserved.

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Valvular heart disease Valvular heart diseases are both acquired and congenital. The congenital/familial clustering and heritability are common for heart valve defects: • Bicuspid aortic valve (BAV) • Myxomatous mitral valve prolapse (MVP) Between days 31 and 35 of embryonic development, cardiac looping completes, and cardiac valve development begins. During the molecular pathways that form mature leaflets, individual valve cusps to specific endocardial cushion progenitors in valvulogenesis in the later stage involves periostin, a component of the extracellular matrix protein and other genetic predispositions that predict valvular disorders that complicate therapeutic outcomes and prognosis later in life.

Mitral valve prolapse Genetic predispositions involved in mitral valve disorders: • The periostin gene • Linkage chromosome 11, 13, 16 (MVP 1, 2, 3) • Filamin A gene mutation • Genetic anomalies and polymorphisms: • FBN1 • Urokinase plasminogen activator • TGF-b1 gene C-509T and T869C polymorphism • TGFbR2 (Chr 3p24.2-p25) mutations • Filamin A gene mutation (Chr Xq28) • PLAU gene T4065C polymorphisms • Collagen IIIa1 exon 31 G2209A polymorphisms, particularly with GG genotype • Angiotensinogen gene M235T polymorphisms, particularly with TT genotype and T allele • FBN1 exon 15 TT and exon 27 GG polymorphisms • ACE-I gene (Chr 17q23) insertion/deletion polymorphisms affecting intron 16 • Angiotensin II type 1 receptor gene A1166C polymorphism, particularly with C allele • FBN1 56 GC intronic polymorphism • Collagen type I, III, V, XI, and tenascin mutations • Collagen type II and XI mutations • Elastin gene mutation • Collagen type I mutation • ATP-binding cassette protein ABCC6 mutation

Chapter 10 Chamber and valve diseases

MVP is a common disorder as a response to a genetically predisposed mitral valve to repetitive mechanical stress. The cells secreting excessive levels of catabolic enzymes result in collagen degradation, deposition of proteoglycans, and leaflet remodeling. Symptoms of MVP syndrome include chest pain, dyspnea, dysrhythmia, anxiety, and syncope. Complications involve mitral regurgitation, congestive heart failure, infective endocarditis, arrhythmias, and sudden death. MVP is characterized by structural distortions including: • Fibromyxomatous degeneration of the mitral valve • Progressive thickening and expansion of the any of the 1, 2, 3, or 4 developed leaflets • Lengthening of the chordae tendineae • Displacement of the leaflets into the left atrium during systole Diseases and disorders associated with or affected by MVP: • Atrial fibrillation • Heart murmur • Hypertension • Infective endocarditis • Marfan syndrome • Mitral valve stenosis • Myxomatous degeneration

Bicuspid aortic valve Nonsyndromic genetic or familial: • NOTCH1 missense and frame shift mutations • Linkage to locus on Chr 5q, 13q, 18q • GATA5 missense mutations Syndromic with other cardiovascular malformation: • Andersen syndromedKCNJ2 mutation (Chr 17q) • Thoracic aortic aneurysm and dissection syndrome (TAAD)d ACTA2 mutation (Chr 10q) • Marfan syndromedFibrillin1 mutation (Chr 15q) • William Beuren syndromedElastin mutation (Chr 7q) • Turner syndrome (45XO karyotype) BAV is a common congenital or familial malformation of the aortic valve with one to four cusps rather than three. It can occur with other diseases such as Turner syndrome, Williams-Beuren syndrome, Andersen syndrome, coarctation of the aorta, murmur and other septal defects, and hypoplastic left heart syndrome.

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Current medications • • • •

Anticoagulants/blood thinners Diuretics Antiarrhythmics Beta blockers

Traditional Chinese medicine See Chapter 9.

Nutritional supplements See Chapter 9.

Pharmaceutical drugs See Chapter 9.

Acute and chronic stages See Chapter 9. In many cases surgery is necessary to preserve cardiac function. Options include: • Heart valve repair • Heart valve replacement • Mechanical valve replacement • Biological valve replacement

Further Reading Ermakov S, Gulhar R, Lim L, et al. Left ventricular mechanical dispersion predicts arrhythmic risk in mitral valve prolapse. Heart. 2019;105(14): 1063e1069. https://doi.org/10.1136/heartjnl-2018-314269. lez-Mansilla A, Martinez-Legazpi P, Prieto A, et al. Valve area and the risk Gonza of overestimating aortic stenosis. Heart. 2019;105(12):911e919. https:// doi.org/10.1136/heartjnl-2018-314482. Lee CH, Laurence DW, Ross CJ, et al. Mechanics of the tricuspid valve-from clinical diagnosis/treatment, in-vivo and in-vitro investigations, to patientspecific biomechanical modeling. Bioengineering (Basel). 2019;6(2):47. https://doi.org/10.3390/bioengineering6020047. Published 2019 May 22. Shah M, Jorde UP. Percutaneous mitral valve interventions (repair): current indications and future perspectives. Front Cardiovasc Med. 2019;6:88. https://doi.org/10.3389/fcvm.2019.00088. Published 2019 Jul 12. Yu W, Ma X, Xu J, et al. VGLL4 plays a critical role in heart valve development and homeostasis. PLoS Genet. 2019;15(2):e1007977. https://doi.org/10.1371/ journal.pgen.1007977. Published 2019 Feb 21.

11 Vascular diseases Chapter Objectives 1. Introduce vascular diseases as seen in integrative cardiovascular Chinese medicine. 2. Introduce peripheral vascular disease and deep vein thrombosis. 3. Introduce stroke. 4. Introduce traditional Chinese medicine formulas and their actions. 5. Introduce nutritional supplements and their active constituents, benefits, and cautions. 6. Introduce pharmaceutical drugs and their actions and pharmacogenetics. 7. Discuss therapies for the acute and chronic stages. 8. Discuss therapies for the recovery and prevention stages.

Background • Peripheral vascular diseases • Stroke Inflammatory markers: • C-reactive protein • Soluble intercellular adhesion molecule-1 • Interleukin-6 • P-selectin Genetic markers: • Interleukin-27 in the development of atherosclerosis • IL-27p28 gene polymorphisms • Premature coronary artery disease • Cardiovascular risk factor • Four IL-27p28 gene polymorphisms • Premature coronary artery disease • rs40837 A allele • Lower risk of insulin resistance

Medical Empathy, Pharmacological Systems, and Treatment Strategies in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817574-3.00011-4 Copyright © 2020 Elsevier Inc. All rights reserved.

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• Folate one-carbon metabolism pathway • Within the pathway, methionine breaks down homocysteine e ALDH1L1 gene e Methylation of proteins, affecting control of genes that are turned on or off as in DNA and RNA e Abnormally high blood levels of homocysteine are associated with stroke and cardiovascular diseases (also in dementia).

Peripheral vascular disease and deep vein thrombosis Both 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 is 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. 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 and is 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 lifethreatening 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.

Chapter 11 Vascular diseases

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

Stroke This is a condition involving two types: ischemic, which is a lack of blood flow, or hemorrhagic, which is blood flow out to the brain, both of which result in functional and motor disorders and cell death. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. The symptoms of a stroke can be transient or permanent.

Current medications Peripheral vascular disease • 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

Stroke • • • • •

Anticoagulants Antiplatelets Tissue plasminogen activator Statins Antihypertensives: • ACE inhibitors • Beta blockers • Calcium channel blockers

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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

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

Shen fu decoction Gui pi decoction

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

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

Chapter 11 Vascular diseases

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, affect prothrombin time and platelet funtion, 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 • Dabigatran: prevents 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 reduce 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

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units designated for inactivation of factor Xa by increasing antithrombin III activity. The measurement is established without checking the PTT or activated PTT. 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 These drugs are coumarins, which 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 international normalized ratio of 2e3. • 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, myocardial infarction, and as a prophylaxis and management thereafter. Patients are often given heparin and aspirin as well. • Alteplase • Reteplase • Tenecteplase

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 of PVD and DVT • During the chronic stage of CAD conditions that manifest 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

Chapter 11 Vascular diseases

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 ndez-Ferna ndez C, Adeva-Andany MM, Ameneiros-Rodríguez E, Ferna Domínguez-Montero A, Funcasta-Calderón R. Insulin resistance is associated with subclinical vascular disease in humans. World J Diabetes. 2019;10(2): 63e77. https://doi.org/10.4239/wjd.v10.i2.63. Flentje A, Kalsi R, Monahan TS. Small GTPases and their role in vascular disease. Int J Mol Sci. 2019;20(4):917. https://doi.org/10.3390/ijms20040917. Published 2019 Feb 20. Leeper NJ, Maegdefessel L. Non-coding RNAs: key regulators of smooth muscle cell fate in vascular disease. Cardiovasc Res. 2018;114(4):611e621. https:// doi.org/10.1093/cvr/cvx249. Liu Z, Khalil RA. Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem Pharmacol. 2018;153: 91e122. https://doi.org/10.1016/j.bcp.2018.02.012. Sasaki N, Itakura Y, Toyoda M. Gangliosides contribute to vascular insulin resistance. Int J Mol Sci. 2019;20(8):1819. https://doi.org/10.3390/ ijms20081819. Published 2019 Apr 12. Satılmıs S, Karabulut A. Correlation between red cell distribution width and peripheral vascular disease severity and complexity. Med Sci (Basel). 2019; 7(7):77. https://doi.org/10.3390/medsci7070077. Published 2019 Jul 9. Shafi S, Ansari HR, Bahitham W, Aouabdi S. The impact of natural antioxidants on the regenerative potential of vascular cells. Front Cardiovasc Med. 2019;6: 28. https://doi.org/10.3389/fcvm.2019.00028. Published 2019 Mar 22.

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Strassheim D, Gerasimovskaya E, Irwin D, Dempsey EC, Stenmark K, Karoor V. RhoGTPase in vascular disease. Cells. 2019;8(6):551. https://doi.org/10.3390/ cells8060551. Published 2019 Jun 6. Wang X, Khalil RA. Matrix metalloproteinases, vascular remodeling, and vascular disease. Adv Pharmacol. 2018;81:241e330. https://doi.org/10.1016/ bs.apha.2017.08.002.

Index ‘Note: Page numbers followed “t” indicates tables.’ ACE inhibitor formulas, 67, 67t Active pharmaceutical ingredient, 90 cardiovascular pharmacology, 90 clinical pharmacology, 90 pharmacogenetics, 90 pharmacogenomics, 90 posology, 90 Acute stage, 3, 4t, 96e99 arrhythmia, 96 blood pressure, 95e96 diuretics, 100 hypertension/beta blockers, 99 nutrients, 99 hypertension/calcium channel blockers, 99e100 lipidemia, 100e101 monoamine oxidase inhibitors (MAOIs), 96e97 positive inotropes, 101 selective serotonin reuptake inhibitors (SSRIs), 96e97 statins, 100e101 traditional Chinese medicine (TCM), 97 antiglycemics, 98e99 antithrombotics, 97 atherosclerotics, 98 nutrients, 97 Alpha/beta-adrenergic agonists, 35 Amiodarone, 33t Angiotensin-converting enzyme inhibitor nutrients L-carnitine, 82 cod liver oil, 81 coenzyme Q-10, 81 magnesium sulfate, 82

niacin, 82 Antiarrhythmic drugs, 26t Antiarrhythmic formulas, 65, 65t Antiarrhythmic nutrients calcium chloride, 75 cod liver oil, 75 coenzyme Q10, 75 magnesium sulfate, 75e76 sodium bicarbonate, 76 Antibiotic formulas, 66, 66t Antibiotic nutrients selenium, 77 vitamin C, 77 vitamin D, 77 vitamin E, 77 Anticoagulants, 36, 37t Anticonvulsants, 35, 36t Antiglycemic formulas, 67, 67t Antiglycemics, 42 Antiglycerides, 37e38, 39t Antihypertensive formulas, 65, 65t Antihypertensive nutrients, 73e75 alpha lipoic acid, 73 chromium, 73e74 cod liver oil, 73 coenzyme Q-10, 73 folic acid, 74 magnesium, 73e74 potassium, 74 selenium, 74 vanadium, 74 vitamin B6, 74 zinc, 74e75 Antihypertensives, 39, 41t Antilipidemic nutrients alpha lipoic acid, 77e78 alpha-lipoic acid, 79e80 berberine, 80

chromium, 78, 80 cod liver oil, 78 coenzyme Q-10, 78 folic acid, 79 magnesium, 78, 80 melatonin, 80 niacin, 78e79 omega-3 fatty acids, 80 potassium, 79 probiotics, 80e81 selenium, 79 vanadium, 79, 81 vitamin B-1, 81 vitamin B6, 79 vitamin D, 81 zinc, 79 Antilipid formulas, 66e67, 67t Antiplatelets, 37 Antithrombotic formulas, 66, 66t Antithrombotic nutrients bioflavonoids, 76 digestive enzymes, 76 essential fatty acids, 76 lumbrokinase, 77 nattokinase, 76 Aspirin, 37t Attuning, 20 Beta 1 adrenergic agonists, 35 Beta 2 adrenergic agonists, 35 Bile acid sequestrants, 39t Cardiac action potentials, 26t Cardiac rhythm diseases acute and chronic stages, 160e162 alpha/beta-adrenergic agonists, 159e160 AV block, 154

178

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Cardiac rhythm diseases (Continued)

beta 1/beta 2 adrenergic agonists, 160 class IA antidysrhythmics, 157e158 class IB antidysrhythmics, 158 class IC antidysrhythmics, 158 class III antidysrhythmics, 159 class V antidysrhythmics, 159 current medications/ treatment, 154 heart blocks, 151e154 arrhythmogenic right ventricular dysplasia (ARVD), 153e154 atrioventricular (AV) block, 151e152 ventricular arrhythmias, 153 nutritional supplements, 155e156 calcium chloride, 155 L-carnitine, 155 cod liver oil, 155 magnesium sulfate, 155 sodium bicarbonate, 155e156 pharmaceutical drugs, 156e160, 156te157t traditional Chinese medicine, 154 Chamber/valve diseases acute and chronic stages, 168 arrhythmogenic right ventricular dysplasia, 165 atrioventricular block, 165 bicuspid aortic valve, 167 current medications, 168 mitral valve prolapse, 166e167 nutritional supplements, 168 pharmaceutical drugs, 168 traditional Chinese medicine, 168 valvular heart disease, 166e167 ventricular arrhythmias, 165

Chronic stage, 5, 9t, 101e102 adenosine, 103 amiodarone, 103e104 antiglycemics, 109e110 antithrombotics, 108e109 arrhythmia, 102e103 atherosclerotics, 109 beta blockers, 104 blood pressure, 101e102 calcium channel blockers, 104 disopyramide, 105 diuretics, 112e115 dronedarone, 104e105 flecainide, 105e106 hypertension, 110e111 hypertension/beta blockers, 111 hypertension/calcium channel blocker, 111e112 lidocaine, 106 lipidemia, 112e114 mexiletine, 106 positive inotropes, 114e115 procainamide, 106e107 propafenone, 107 quinidine, 108 sotalol, 108 statin, 112e113 statins, 113e114 Class IA antiarrhythmics, 27, 28t Class IB antidysrhythmics, 29, 29t Class IC antidysrhythmics, 30, 31t Class III antidysrhythmics, 31, 33t Class V antidysrhythmics, 33, 33t Clopidogrel, 37t Constitutional theories, 54, 54te61t Deliberative model, 21t Detached cognition, 19 Diabetes acute and chronic stages, 147e148

current medications, 143e144 glucose studies, 143 HbA1c, 143e147 management, 142e143 nutritional supplements, 144e145 pharmaceutical drugs, 146e147 prediabetes, 142 recovery and prevention stages, 148e149 traditional chinese medicine, 144, 144t type 2 diabetes, 142e143 Dietary Supplement and Health Education Act (DSHEA), 71e72 Disopyramide, 28t Diuretic formulas, 68, 68t Diuretic nutrients magnesium, 82 potassium, 82 vitamin C, 82e83 Diuretics, 43, 44t Doctor/patient relationship. See Physician/patient relationship Dronedarone, 33t Emotional needs, 20 Emotional resonance, 19 Ezetimibe, 39t Fibrates, 39t Flecainide, 31t Han dynasties, 48e49, 49t Herbal preparation, 61e62 Hypertension acute and chronic stages, 138e141 current medications, 134 JNC 7 classification, 132, 132t management, 132e133, 133t nutritional supplements, 134e136

Index

pharmaceutical drugs, 136e138 primary hypertension, 131 secondary hypertension, 131 traditional chinese medicine, 134 Informative model, 21t Injected drugs, 42e43, 42t Inotropics, 34e35 Interpretive model, 21t Isoproterenol, 35t Lidocaine, 29t Lipid-lowering agents, 39t Lipoprotein disorders acute and chronic stages, 130 alpha lipoic acid, 126 chromium, 127 cod liver oil, 126 coenzyme Q-10, 126 current medications, 126e128 folic acid, 127 high blood pressure drugs, 129e130 magnesium, 127 niacin, 127 nutritional supplements, 126e127 pharmaceutical drugs, 128 potassium, 127 recovery and prevention stages, 130 selenium, 127 vanadium, 127 vitamin B6, 127 zinc, 128 Low molecular weight heparins, 37t Medical empathy attuning, 20 detached cognition, 19 emotional resonance, 19 Medical journal format, 20 Mexiletine, 29t

Ming dynasty, 51e54 Nitrates, 45, 45t Norepinephrine, 35t Nutritional supplements angiotensin-converting enzyme inhibitor nutrients. See Angiotensin-converting enzyme inhibitor nutrients antiarrhythmic nutrients. See Antiarrhythmic nutrients antibiotic nutrients. See Antibiotic nutrients antihypertensive nutrients, 73e75. See also Antihypertensive nutrients antilipidemic nutrients. See Antilipidemic nutrients antithrombotic nutrients. See Antithrombotic nutrients California proposition 65, 72e73 defining and labeling finished products, 70 diuretic nutrients. See Diuretic nutrients Federal Food, Drug and Cosmetic Act, 1938, 70 future practices regulation, 71e73 government regulations, 70e71 United States, 69 Nutrition Labeling and Education Act (NLEA), 1990, 71e72 Paternalistic approach, 21t Patient compliance, 20, 21t medical journal format, 20 Pharmaceutical drugs islamic medicine, 87e88 modern history, 88e89 pharmacodynamics, 86

179

pharmacokinetics, 86 recorded transition toward modern pharmacology, 87 therapeutic index, 89e90 western medicine pharmacology, 86e87 Physician/patient relationship, 21 approaches, 21t Prasugrel, 37t Prescription plant sterols, 39t Prevention stage, 13, 16t antithrombotics, 122 atherosclerotics, 122 blood pressure, 121e122 diuretics, 123 hypertension/calcium channel blockers, 122e123 lipidemia, 124 nitrates, 123e124 statins, 124 Procainamide, 28t Propafenone, 31t Qin dynasties, 48e49, 49t Qing dynasty, 52 Quinidine, 28t Recovery stage, 10, 13t antiglycemics, 116 antithrombotics, 115e116 atherosclerotics, 116 blood pressure, 115 definition, 118 diuretics, 117 heart failure nitrates, 118e119 hypertension/calcium channel blockers, 117e118 nitrates, 119e121 pharmacological therapy, 118e119 positive inotropes, 121

180

Index

Song dynasty, 50e51 Sotalol, 33t Statins, 39t Sui dynasty, 49e51 Tang dynasty, 49e51 Therapeutic index, 89e90 active pharmaceutical ingredient, 90 narrow index, 89 wide index, 89 Therapeutic rationale, treatment acute stage, 3, 4t chronic stage, 5, 9t prevention stage, 13, 16t recovery stage, 10, 13t Thrombolytics, 37t Ticagrelor, 37t Traditional Chinese medicine ACE inhibitor formulas, 67, 67t antiarrhythmic formulas, 65, 65t antibiotic formulas, 66, 66t antiglycemic formulas, 67, 67t antihypertensive formulas, 65, 65t

antilipid formulas, 66e67, 67t antithrombotic formulas, 66, 66t 20th century, 52e53 21st century, 54 common herbs, 63e68, 64t constitutional theories, 54, 54te61t delivery types, 61e62 diuretic formulas, 68, 68t Han dynasties, 48e49, 49t herbal preparation, 61e62 history, 47e48 Ming dynasty, 51e54 Qin dynasties, 48e49, 49t Qing dynasty, 52 Song dynasty, 50e51 Sui dynasty, 49e51 Tang dynasty, 49e51 Vascular diseases acute and chronic stages, 174e175 anticoagulants, 173 background, 169e171 bioflavonoids, 172 current medications, 171

deep vein thrombosis (DVT), 170e171 digestive enzymes, 172 essential fatty acids, 172 low molecular weight heparins, 173e174 lumbrokinase, 173 nattokinase, 173 nutritional supplements, 172e173 peripheral vascular disease (PVD), 170e171 pharmaceutical drugs, 173e174 recovery and prevention stages, 175 stroke, 171 thrombolytics, 174 traditional Chinese medicine, 172, 172t vitamin K antagonists, 174 Western medicine pharmacology, 86e87 Zinc, 74e75, 79, 128