Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care Alan David Kaye Adam M. Kaye Richard D. Urman Editors 123 Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care Alan David Kaye • Adam M. Kaye Richard D. Urman Editors Essentials of Pharmacology for Anesthesia, Pain Medicine, and Critical Care Editors Alan David Kaye, MD, PhD Richard D. Urman, MD, MBA Departments of Anesthesiology Department of Anesthesiology and Pharmacology Perioperative and Pain Medicine LSU Health Sciences Center Brigham and Women’s Hospital New Orleans , LA Harvard Medical School USA Boston , MA USA LSU Interim Hospital and Ochsner Kenner Hospital Ambulatory Care Center New Orleans , LA Brigham and Women’s Hospital USA Chestnut Hill , MA Adam M. Kaye, PharmD USA Department of Pharmacy Practice Thomas J. Long School of Pharmacy Center for Perioperative Management and Health Sciences and Medical Informatics University of the Pacifi c Department of Anesthesiology Stockton , CA Perioperative and Pain Medicine USA Brigham and Women’s Hospital Boston , MA USA ISBN 978-1-4614-8947-4 ISBN 978-1-4614-8948-1 (eBook) DOI 10.1007/978-1-4614-8948-1 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2014948072 © Springer Science+Business Media New York 2015 T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. T he use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Adam and I wish to thank our parents, Florence Feldman and Joel Kaye, for their love and support. We also want to thank our stepparents, Andrea Kaye and the late Gideon Feldman, along with the Gittelman family for always helping and treating us with love and kindness over our lifetime. All three of us wish to thank Dr. Jonathan Jahr and Dr. Karina Gritsenko, MD, for their extra help in the preparation of this book. This book has been the largest project I have undertaken in many decades. I wish to dedicate this book to everyone interested to learn about anesthesia and pharmacology. I also wish to dedicate this book to my family: my wife Dr. Kim Kaye, my son Aaron, and my daughter Rachel. I also wish to thank my pharmacology and anesthesia mentors, Dr. Alan W. Grogono, MD; Dr. Philip J. Kadowitz, PhD; and Dr. Bobby D. Nossaman, MD, for allowing me to complete my PhD in pharmacology while serving my full-time duties at Tulane Medical Center many years ago. Alan D. Kaye, MD, PhD I would like to dedicate this book to my wife Beth Kaye and daughter Jessica Kaye and thank them from the bottom of my heart for their patience and love. I would like to thank James W. Blankenship, PhD, Emeritus Professor, Department of Physiology and Pharmacology, for stimulating my interest while a student at the Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacifi c. Most importantly, I would like to thank my older and wiser brother Alan Kaye for being my fi rst teacher and best friend. Adam M. Kaye, PharmD This book covers extensive amount of material highly relevant to the practice of anesthesiology, pain, and critical care medicine. I would like to thank my colleagues, students, and mentors for encouraging me to undertake this massive project. I hope that current and future generations of practitioners and trainees will benefi t from my efforts. I would like to thank my wife Zina Matlyuk, MD, for her editorial assistance and advice. I wish to dedicate this book to Zina, my daughters Abigail and Isabelle, and my parents Dennis and Tanya Urman. Richard D. Urman, MD, MBA Foreword T he word pharmacology is derived from the Greek φάρμακον, pharmakon , and -λογία, -logia , “study of.” Strangely φάρμακον meant “poison” in classic Greek but came to mean “drug” in the modern language. But what is a drug? It can be described as anything manufactured, natural, or endogenous that exerts some physi- ological cellular. Pharmacology is the study of the interactions between a living organism and substances that have an impact on normal or abnormal function. The division between food and herbs is somewhat blurred as the latter prepara- tions are not governed by the Food and Drug Administration but rather held to the standards of the food industry where trials of effectiveness and universal testing of safety are not required. However, the word “drug” is believed to originate from an old French word “drogue” and later from the Dutch “droge-vate,” which referred to the drying or preserving barrels used to store plants for medicinal use (in other words, drugs and herbs are the same thing). Indeed, today about 30 % of our medi- cines derive directly from herbs, the only difference being that drugs have specifi ed amounts of active ingredients and herbs are not regulated as to content. Some of our earliest medical texts have centered on medicinal therapies. The Yellow Emperor’s Classic of Internal Medicine , collected around 2600 BC, describes plants and foods that are applicable to the maintenance of health and the treatment of specifi cally diseased organs. Writing in the fi rst century AD, Pedanius Dioscorides (circa 40–90 AD), a Greek physician, pharmacologist, and botanist, authored a 5-volume encyclopedia about some 600 herbal medicines that was the standard ref- erence for 1,500 years. During the Renaissance the book was read in Latin, Greek, and Arabic. Before that, in the seventh century AD, Paulus Aeginata, also Greek, in a monumental act of plagiarism (although he does give some acknowledgements), collected all the works of Hippocrates, Galen, Dioscorides, and Aretaeus, among others, and produced seven books, the last of which is over 600 pages long and is devoted entirely to herbal remedies. In all of these works, many of the drugs we use today such as opium, aspirin, cannabis, castor oil, mandragora (atropine, scopol- amine), cocaine, physostigmine, and digitalis among many others are listed. It is to the efforts of William Withering to understand the effects of this last herb, digitalis, from the purple foxglove, that we see the foundations of pharmacology. In his text, vii viii Foreword An Account of the Foxglove , Withering relates how he achieved the potion from an old lady in Shropshire and sent samples to his colleagues to gauge under which circumstances the extract would relieve lower extremity edema and other signs of heart failure. One of the frightening experiences the new resident in anesthesia has is encoun- tering the sometimes bewildering array of medications that can take patients to the door of death and then (hopefully) bring them back. With an aging population come more comorbidities and the risk of drug interactions increases. Ever-increasing complexity of machines, requirements for monitoring, and mandated data collec- tion all add to the stress of the perioperative period. The ability to turn to a concise yet easy to read comprehensive text on the drugs we use daily is something to be treasured and an immense help for the practitioner. In this, the latest of a long line of pharmaceutical texts, Drs. Kaye and Urman are to be congratulated on gathering together such a wide range of authors from many different venues and perspectives. The coverage of topics within E ssentials of Pharmacology is indeed encyclopedic. It is my hope that this book will allow practitioners of anesthesia to embrace the topic of pharmacology and thus gain confi dence in the knowledge that their patients will be cared for appropriately and safely. New York , NY , USA Elizabeth A. M. Frost , MD Pref ace In many academic papers that we have read and written over the years, drugs are described in abstract and theoretical ways. These drugs might possess novel mecha- nisms or improved duration of activity. These agents might be less toxic or possess reduced side effects. Clearly, drugs dramatically affect our life spans, including our quality of life. As the years have gone by, we have a much greater appreciation for their wonders. I t was not long ago that our life spans were much shorter. Tens of thousands of people died due to plague, an organism easily treated with sulfonamides. It is an astonishing fact that dysentery was the single greatest cause of death of Confederate and Union soldiers during our epic Civil War. Some of our greatest fi gures in history had shortened lives related to what we would now consider very treatable states. George Washington probably died of acute bacterial epiglottis. The poet Lord Byron died prematurely from an epileptic seizure. Harry Houdini probably died from acute appendicitis. Arthur Ashe died, in part, from transmission of the human immune defi ciency virus. Thousands of people die each year from NSAID-mediated silent gastrointestinal bleeding. Principally during the last 50 years, we have dramatically increased our under- standing of disease states, and the technology to detect these states has also grown signifi cantly. Drug development has resulted in an increasing longevity, reduced pain, and enhanced quality of life. On a daily basis in every community, an anesthe- siologist is called to a code with a patient appearing lifeless and without hope and delivers atropine, epinephrine, sodium bicarbonate, and calcium, and the patient is ultimately rescued and stabilized. These drug-mediated miracles are commonplace and routine in our practices. In the last decade, we have seen complete cataloging of the entire human genome and an increase in drug targets from fi ve hundred to well over one thousand. No longer is it a guaranteed death sentence to have human immune defi ciency virus, many types of cancers, or sepsis. There is now new hope in drug targeting for vas- cular atherosclerosis, diabetes mellitus, cardiomyopathy, many cancers, and even Alzheimer’s disease. We fi nd ourselves constantly at a new beginning with drugs, including in our fi elds of anesthesia and pain medicine. Structural activity ix