THIRD EDITION Karch’s Pathology of Drug Abuse © 2002 by CRC Press LLC THIRD EDITION Karch’s Pathology of Drug Abuse Steven B. Karch, M.D. Medical Director Las Vegas Fire and Rescue and Assistant Medical Examiner City and County of San Francisco CRC PR ESS Boca Raton London New York Washington, D.C. © 2002 by CRC Press LLC FrontmatterFM Page ii Thursday, November 8, 2001 2:09 PM Library of Congress Cataloging-in-Publication Data Karch, Steven B. Karch’s pathology of drug abuse / Steven B. Karch.—3rd ed. p. ; cm. Includes bibliographical references and index. ISBN 0-8493-0343-5 1. Drugs of abuse—Pathophysiology. 2. Drugs of abuse—Toxicology. I. Title. [DNLM: 1. Substance-Related Disorders—physiopathology. 2. Anabolic Steroids— adverse effects. 3. Cocaine—adverse effects. 4. Designer Drugs—adverse effects. 5. Narcotics—adverse effects. 6. Substance-Related Disorders—history. WM 270 K18p 2001] RM316 .K37 2001 615¢.78—dc21 2001036559 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 Corporate Blvd. N.W., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. © 2002 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 1-8493-0343-5 Library of Congress Card Number 2001036559 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper © 2002 by CRC Press LLC FMnew.fm Page iii Tuesday, November 6, 2001 7:18 AM Dedication For Donna, my wife of 25 years, for our friends everywhere, and for Sam. © 2002 by CRC Press LLC FMnew.fm Page v Tuesday, November 6, 2001 7:18 AM Preface to the first edition Physicians deal with the consequences of drug abuse on a daily basis, but information about the basic pathology of abused drugs is hard to come by. Hundreds of papers have been published describing the effects of drug abuse on brain neurochemistry, but practi- tioners are hard pressed to find out how cocaine affects blood vessels or how heroin affects the lungs. I hope this book supplies the information they need. While far from encyclo- pedic, I think the book does provide answers to most of the questions physicians ask when they are confronted with cases of drug-related death or disability. In the course of writing the sections on heroin, I was surprised to discover that more than 20 years have elapsed since the first papers were published by Milton Helpern, Charles Wetli, and Michael Baden. Since that time, our government has done little to foster research into the pathology of abused drugs, and knowledge has advanced very little. With the advent of the great HIV pandemic, there may be a price to pay for this lack of knowledge, and for the failure to foster meaningful research. Perhaps with changing government priorities this situation will some day be rectified. Finally, readers of the book will notice two important omissions: alcohol and mari- juana. The reason for not dealing with the former is that alcohol requires its own book. The reason for not discussing the latter is that there isn’t enough good anatomic pathology to write about, although recently there have been some interesting studies dealing with marijuana toxicology. I hope this subject can be added in future editions. Steven B. Karch, M.D. Berkeley, California © 2002 by CRC Press LLC FMnew.fm Page vi Tuesday, November 6, 2001 7:18 AM Preface to the second edition Nearly 900 new references have been added since the first edition. The large increase in number is explained partly by the addition of new subjects, such as solvent abuse. Most of the increase is simply due to increased interest in drug abuse, which is reflected by an increase in the number of papers being published. This increase became apparent late in 1991, and already seems to have peaked. This edition contains 233 new references from 1993, 224 from 1994, and 110 from the first 6 months of 1995. There have been some major advances since the first edition was published, but most of these have been in the fields of molecular biology and neurochemistry. The character- ization of receptor changes in agitated delirium and the cloning of opiate receptors come quickly to mind. By comparison, advances in the field of pathology have been pitifully few. Fewer than 2% of the new references added to this edition have anything to do with anatomy or pathology. Whether this dismal finding reflects a lack of interest among pathologists, or simply is a function of the fact that pathologists have no voice on the various panels that control drug abuse research funding, is not clear. I suspect, however, it is the latter. I was gratified by the response to the first edition, and pleased that so many have found the book to be useful. I have tried to make this version even better. Perhaps there will be some new pathology to describe in the next edition. Steven B. Karch, M.D. Berkeley, California © 2002 by CRC Press LLC FMnew.fm Page vii Tuesday, November 6, 2001 7:18 AM Preface to the third edition Six years have elapsed since publication of the second edition of The Pathology of Drug Abuse (now titled Karch’s Pathology of Drug Abuse). Important advances in the molecular biology of addiction have occurred since then. Some of these advances are directly relevant to the clinical disciplines of pathology and toxicology. Recent discoveries about heritable “channelopathies” and their role in the causation of sudden cardiac death are particularly exciting. Nonetheless, the pathology of drug abuse remains essentially an orphan science. When the first edition of this book was published in 1992, the Drug Abuse Warning Network (DAWN) survey reported 3465 cocaine-related deaths, and there were 1044 Medline citations for cocaine. The number of cocaine-related deaths had increased to nearly 5000 in 1999, but the number of published studies on cocaine was unchanged. Similarly depressing figures could be quoted about heroin and heroin-related research. Government sponsorship for pathology and postmortem toxicology remains nonexistent. Even so, more than 800 new references have been added to this edition, and there is an emerging acceptance of the notion that toxicology is not the same as therapeutic drug monitoring. Forensic pathologists now understand that measuring the blood concentra- tions of an abused drug does not explain how and why that drug is toxic or determine a cause of death. Acceptance of this idea is no small thing, and perhaps more progress has been made than appears. As the author of this book, I continue to be gratified by the response it has received, especially when someone tells me how useful it has been in his or her search for answers to difficult problems. I am hopeful that readers will continue to be pleased by this book, even if our fundamental understanding of the problems has not advanced by quite as much as I would have liked. Steven B. Karch, M.D. Berkeley, California © 2002 by CRC Press LLC