Karch's Pathology of Drug Abuse, Third Edition

534 Pages·2001·78.22 MB·English

by  Steven B. Karch

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
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No claim to original U.S. Government works
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Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
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© 2002 by CRC Press LLC
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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
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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
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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
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Acknowledgments
All of my teaching files were lost in the Oakland Hills wildfire of 1991. If it were not for
the generous assistance of the contributors listed below, this book would have had a lot
fewer illustrations!
American Society of Clinical Pathologists, Chicago, Illinois
Dr. Margaret Billingham, Department of Cardiovascular Surgery, Stanford University School
of Medicine
Dr. Rosario Barroso-Moguel, Instituto Nacional De Neurologia Y Neurocirogia, Mexico City
Dr. Kari Blaho, University of Tennessee Medical Group, Memphis, Tennessee
Dr. Arthur K. Cho, Department of Pharmacology, UCLA School of Medicine
Marcel de Kort, Netherlands Ministry of Health
Dr. Agnes Fogo, Vanderbilt University Medical Center, Nashville, Tennessee
Dr. Werner Franke, Division of Cell Biology, German Cancer Research Center, Heidelberg,
Germany
Dr. Jacques Gilloteaux, Department of Anatomy, College of Medicine, Northeastern Ohio
Universities
Dr. François Gray, Department of Pathology, Hôpital Henri Mondor, Creteil, France
Dr. Peter S. Hersh, Chairman, Department of Ophthalmology, Bronx-Lebanon Hospital
Dr. Marc J. Kaufman, Harvard Medical School and McLean Hospital, Belmont, Massachusetts
Dr. Robert Kloner, Hospital of the Good Samaritan, Los Angeles
Dr. Russell Kridel, University of Texas, Health Sciences Center, Houston
Dr. David A. Krendel, Section of Neurology, The Emory Clinic, Atlanta
Professor M. Maillet, Hôpital Lariboisère, Paris
National Library of Medicine, Bethesda, Maryland
Marilyn Masek, Laboratory of Cardiovascular Pathology, Stanford University School of
Medicine
Dr. Alan L. Morrison, Department of Neuropathology, Armed Forces Institute of Pathology,
Washington, D.C.
Dr. Morton A. Meyers, Department of Radiology, SUNY at Stony Brook, New York
Dr. José Peña, Facultad De Medicina, Universidad De Cordoba, Spain
Dr. Giuseppe G. Pietra, Director, Division of Anatomic Pathology, Hospital of the University
of Pennsylvania
Dr. N. G. Ryley, University of Oxford, Nuffield Department of Pathology and Bacteriology,
Oxford, England
Stephen M. Roberts, University of Florida, Center for Environmental and Human Toxicology
Dr. J. M. Soares, Faculty of Sport Sciences, University of Porto, Portugal
© 2002 by CRC Press LLC