Karch's Pathology of Drug Abuse, Fourth Edition

738 Pages·2008·23.11 MB·English

by  MD

KARCH’S
PATHOLOGY OF
DRUG ABUSE
F O U R T H E D I T I O N
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KARCH’S
PATHOLOGY OF
DRUG ABUSE
F O U R T H E D I T I O N
STEVEN B. KARCH, MD, FFFLM
Boca Raton London New York
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Library of Congress Cataloging‑in‑Publication Data
Karch, Steven B.
Karch’s pathology of drug abuse / Steven B. Karch. ‑‑ 4th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978‑0‑8493‑7880‑5 (hardcover : alk. paper)
1. Drug abuse‑‑Pathophysiology. 2. Drugs of abuse‑‑Toxicology. I. Title. II. Title: Pathology of drug
abuse.
[DNLM: 1. Substance‑Related Disorders‑‑physiopathology. 2. Anabolic Agents‑‑adverse effects.
3. Cocaine‑‑adverse effects. 4. Designer Drugs‑‑adverse effects. 5. Narcotics‑‑adverse effects. 6.
Substance‑Related Disorders‑‑history. WM 270 K18k 2009]
RM316.K37 2009
615’.78‑‑dc22 2008039584
Visit the Taylor & Francis Web site at
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Dedication
For my wife Donna and her support, which was often needed, and for Dr. Sheldon Kabaker,
who introduced the two of us and became my closest friend. For Hardwin and Roger,
who try very hard. And for Henry Urich, whose brilliance inspired me, and Margaret
Billingham, whose brilliance, tenacity, and hard work were more than just inspirational.
For Miriam and Sam, who never got to see any of the books, and especially Richard and
Gail Ullman of Princeton, New Jersey—good people and good friends.

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Contents
1 Cocaine.................................................................................................1
References ........................................................................................................................................2
1.1 Incidence of Abuse ..............................................................................................................3
References ........................................................................................................................................6
1.2 Epidemiology .......................................................................................................................6
References ........................................................................................................................................8
1.3 History ..................................................................................................................................9
References ......................................................................................................................................18
1.4 Current Affairs ..................................................................................................................19
1.4.1 Cocaine Availability ..........................................................................................21
1.4.2 Cultivation and Crop Yields ............................................................................22
1.4.3 Paste Production ................................................................................................24
1.4.4 Quality ................................................................................................................28
References ......................................................................................................................................29
1.5 Routes of Ingestion ...........................................................................................................30
1.5.1 Overview .............................................................................................................30
1.5.2 Coca Leaf Chewing ...........................................................................................30
1.5.3 Snorting (Insufflation) ......................................................................................31
1.5.4 Surgical Application ..........................................................................................32
1.5.5 Intravenous Use .................................................................................................33
1.5.6 Genital Application ...........................................................................................34
1.5.7 Dermal Absorption ...........................................................................................34
1.5.8 Inhalation ...........................................................................................................35
1.5.9 Gastrointestinal Absorption ............................................................................37
1.5.10 Special Maternal/Fetal Considerations ..........................................................41
References ......................................................................................................................................43
1.6 Metabolism of Cocaine and Its Metabolites .................................................................47
1.6.1 Cocaine ...............................................................................................................47
1.6.2 Benzoylecgonine (BZE) and Ecgonine Methyl Ester ...................................49
1.6.3 Cocaethylene ......................................................................................................52
1.6.4 Anhydroecgonine Methyl Ester (Methylecgonidine) ...................................54
1.6.5 Norcocaine .........................................................................................................54
References ......................................................................................................................................55
1.7 Fetal Metabolism ...............................................................................................................58
References ......................................................................................................................................59
1.8 Problems of Cocaine Test Interpretation.......................................................................60
1.8.1 Introduction .......................................................................................................60
1.8.2 Tolerance .............................................................................................................61
ii
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iii Contents
1.8.3 Postmortem Redistribution .............................................................................62
1.8.4 Cocaine-Related Deaths ...................................................................................62
1.8.5 Estimating Time of Ingestion ..........................................................................63
1.8.6 Low Cocaine Concentrations ..........................................................................64
1.8.7 Cocaine and Prescription Drug Interactions ................................................65
1.8.8 Adulterants .........................................................................................................66
References ......................................................................................................................................67
1.9 Cocaine Tissue Disposition .............................................................................................69
1.9.1 Human Postmortem Measurement ................................................................70
1.9.2 Brain ....................................................................................................................70
1.9.3 Hair ......................................................................................................................71
1.9.4 Heart ....................................................................................................................72
1.9.5 Kidneys ...............................................................................................................72
1.9.6 Liver .....................................................................................................................73
1.9.7 Skin and Nails ....................................................................................................73
1.9.8 Biofluids ..............................................................................................................76
1.9.8.1 Amniotic Fluid ...............................................................................76
1.9.8.2 Breast Milk .....................................................................................76
1.9.8.3 Fetal Gastric Aspirates ..................................................................77
1.9.8.4 Oral Fluid (Saliva) .........................................................................77
1.9.8.5 Spinal Fluid .....................................................................................78
1.9.8.6 Urine ................................................................................................78
1.9.8.7 Vitreous Humor .............................................................................80
1.9.8.8 Sweat ................................................................................................82
1.9.8.9 Semen ..............................................................................................82
References ......................................................................................................................................82
1.10 Electrophysiology of Sudden Death in Cocaine Abusers ............................................87
1.10.1 Myocardial Remodeling ...................................................................................87
1.10.2 Hypertrophy .......................................................................................................89
1.10.3 QT Dispersion ....................................................................................................93
1.10.4 Ion Channel Remodeling and Interactions ...................................................93
1.10.5 The Theory of “Multiple Hits” .........................................................................94
1.10.6 The Role of Catecholamines .............................................................................96
1.10.7 Mechanisms of Catecholamine Toxicity ........................................................98
1.10.8 Histopathology of Catecholamine Toxicity ...................................................99
1.10.9 Contraction Band Necrosis and Sudden Death ..........................................104
1.10.10 Hereditary Channelopathies ..........................................................................104
References ....................................................................................................................................105
1.11 External Markers of Cocaine Abuse ............................................................................109
1.11.1 Perforated Nasal Septum ................................................................................109
1.11.2 “Parrot Beak” Nails ..........................................................................................110
1.11.3 “Crack Thumb” .................................................................................................111
1.11.4 “Crack Lips” ......................................................................................................111
1.11.5 “Track” Marks ..................................................................................................111
1.11.6 “Crack” Keratitis..............................................................................................113
1.11.7 Dental Erosions and Oral Lesions..................................................................114
1.11.8 “Crack Hands” ..................................................................................................114
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Contents ix
1.11.9 Evidence of Terminal Seizures ......................................................................115
1.11.10 Marks and Mutilation .....................................................................................115
References ....................................................................................................................................115
1.12 Skin Toxicity .....................................................................................................................117
References .....................................................................................................................................118
1.13 Cardiovascular System, General Overview .................................................................119
1.13.1 Myocardial Infarction .....................................................................................119
1.13.2 Microvascular Disease ....................................................................................122
1.13.3 Atheromatous Coronary Artery Disease .....................................................123
1.13.4 Coronary Artery Spasm .................................................................................124
1.13.5 Decreased Flow Reserve .................................................................................125
1.13.6 Centrally Mediated Vascular Disease...........................................................126
1.13.7 HIV-Related Myocardial Disease ..................................................................127
1.13.8 Valvular Heart Disease ...................................................................................128
1.13.9 Aorta and Peripheral Vessels .........................................................................129
1.13.10 Eosinophilic Myocarditis ...............................................................................130
1.13.11 Coronary Artery Dissection ..........................................................................132
1.13.12 Nonatheromatous Coronary Artery Disease ..............................................132
References ....................................................................................................................................132
1.14 Excited Delirium and the Neuroleptic Malignant Syndrome ..................................137
1.14.1 History and Overview of Excited Delirium ................................................137
1.14.2 Excited Delirium and the Redefinition
of “Positional Asphyxia” .................................................................................139
1.14.3 The Exercise Physiology of “Positional Restraint” and “Restraint
Asphyxia” .........................................................................................................140
1.14.4 The Neurochemistry of Excited Delirium ...................................................142
1.14.5 Autopsy Findings .............................................................................................145
1.14.6 The Toxicology of Excited Delirium .............................................................145
1.14.7 Cause of Death Determination......................................................................146
References ....................................................................................................................................148
1.15 Cocaine-Associated Pulmonary Disease .....................................................................150
1.15.1 Barotrauma.......................................................................................................151
1.15.2 Parenchymal Disease ......................................................................................153
1.15.3 Vascular Adaptations ......................................................................................156
References ....................................................................................................................................157
1.16 Neurological Disorders, Introduction .........................................................................162
1.16.1 Cocaine Neurotoxicity ....................................................................................163
1.16.2 Psychiatric Syndromes ....................................................................................164
1.16.3 Ischemic Stroke ................................................................................................165
1.16.4 Cerebral Vasculitis ..........................................................................................167
1.16.5 Subarachnoid and Intraventricular Hemorrhage .......................................169
1.16.6 Seizures .............................................................................................................171
1.16.7 Movement Disorders .......................................................................................173
1.16.8 Blood–Brain Barrier Alterations ...................................................................173
References .....................................................................................................................................174
1.17 Renal Disease ...................................................................................................................179
References ....................................................................................................................................183
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