Karch’s Pathology of Drug Abuse

906 Pages·2015·19.99 MB·English

by  Steven B. Karch

Karch’s
Patholog y
of Drug Abuse
Fifth Edition

Karch’s
Patholog y
of Drug Abuse
Fifth Edition
Steven B. Karch,
MD, FFFLM, FFSSoc
Olaf H. Drummer,
PhD, FRCPA, FFSC

Boca Raton London New York
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Version Date: 20150206
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As always, for my wife Donna for her constant support. For Hardwin and
Roger who, more than anyone else, allowed the process to go forward. For
my parents, who died far too young to have seen any of the editions, and for
kindred spirit Richard Ullman of Princeton, who also died much too young.
My special thanks to Olaf Drummer, who helped me make sense of chemistry
too arcane for a simple pathologist to understand! hanks also to Ruth Swan,
who managed to convert some of my meanderings into sensible English.
And, most of all, to those of you who have come to rely on my book.

Contents
Preface xxv
Authors xxvii
1
Cocaine 1
1.1 Prevalence of Abuse 1
1.2 Epidemiology 5
1.3 History 8
1.4 Current Afairs 19
1.4.1 Cultivation and Crop Yields 20
1.4.2 Cocaine Production 23
1.4.3 Price and Quality 27
1.5 Metabolism of Cocaine and Its Metabolites 28
1.5.1 Cocaine 28
1.5.2 Benzoylecgonine and Ecgonine Methyl Ester 32
1.5.3 Cocaethylene 34
1.5.4 Anhydroecgonine Methyl Ester (Methylecgonidine) 36
1.5.5 Norcocaine 36
1.6 Fetal Metabolism 37
1.7 Routes of Ingestion 38
1.7.1 Overview 38
1.7.2 Coca Leaf Chewing 38
1.7.3 Snorting (Insulation) 39
1.7.4 Surgical Application 40
1.7.5 Intravenous Use 41
1.7.6 Genital Application 42
1.7.7 Dermal Absorption 43
1.7.8 Inhalation 44
1.7.9 Gastrointestinal Absorption 46
1.7.10 Special Maternal/Fetal Considerations 50
1.8 Problems of Cocaine Test Interpretation 52
1.8.1 Introduction 52
1.8.2 Tolerance 53
1.8.3 Postmortem Redistribution 54
1.8.4 Cocaine-Related Deaths 55
1.8.5 Estimating Time of Ingestion 56
1.8.6 Low Cocaine Concentrations 56
1.8.7 Cocaine and Prescription Drug Interactions 58
vii
viii Contents
1.9 Cocaine Adulterants 58
1.9.1 Traditional Adulterants 58
1.9.2 Levamisole/Aminorex 59
1.10 Cocaine Tissue Disposition and Postmortem Redistribution 64
1.10.1 Human Postmortem Measurements 65
1.10.2 Brain 65
1.10.3 Hair 66
1.10.4 Heart 68
1.10.5 Kidneys 69
1.10.6 Liver 69
1.10.7 Skin and Nails and Adipose Tissue 70
1.10.8 Bioluids 72
1.10.8.1 Amniotic Fluid 72
1.10.8.2 Breast Milk 73
1.10.8.3 Fetal Gastric Aspirates and Meconium 74
1.10.8.4 Oral Fluid (Saliva) 74
1.10.8.5 Spinal Fluid 75
1.10.8.6 Urine 76
1.10.8.7 Vitreous Humor 78
1.10.8.8 Sweat 78
1.10.8.9 Semen 79
1.11 Electrophysiology of Sudden Death in Cocaine Abusers 79
1.11.1 QT Dispersion and QT Prolongation 80
1.11.2 Myocardial Remodeling 82
1.11.2.1 Myocardial Hypertrophy 85
1.11.2.2 Electrical Remodeling 89
1.11.2.3 hERG Components 91
1.11.2.4 Fibroblasts and the Interstitium 91
1.11.3 Electrical Vulnerability 93
1.11.4 Catecholamines and Action Potentials 94
1.11.4.1 Adrenergic Receptors 94
1.11.4.2 Histologic Manifestations of Catecholamine

and Cocaine Toxicity 96
1.12 External Markers of Cocaine Abuse 101
1.12.1 Perforated Nasal Septum 101
1.12.2 “Parrot Beak” Nails 102
1.12.3 “Crack humb” 102
1.12.4 “Crack Lips” 103
1.12.5 “Track” Marks 103
1.12.6 “Crack” Keratitis 105
1.12.7 Dental Erosions and Oral Lesions 105
1.12.8 “Crack Hands” 106
1.12.9 Evidence of Terminal Seizures 106
1.12.10 Marks and Mutilation 107
1.13 Skin Toxicity 107
Contents ix
1.14 Cardiovascular System: General Overview 109
1.14.1 Coronary Artery Disease 110
1.14.2 Microvascular Disease 112
1.14.3 Atheromatous Coronary Artery Disease 114
1.14.4 Coronary Artery Spasm 117
1.14.5 HIV-Related Myocardial Disease 118
1.14.6 Valvular Heart Disease 118
1.14.7 Aorta and Peripheral Vessels 118
1.14.8 Eosinophilic Myocarditis 119
1.14.9 Coronary Artery Dissection 120
1.14.10 Nonatheromatous Coronary Artery Disease 121
1.14.11 Accelerated Coronary Artery Disease 121
1.15 Excited Delirium Syndrome 121
1.15.1 History and Overview of Excited Delirium Syndrome 121
1.15.2 Excited Delirium and the Redeinition of “Positional
Asphyxia” 125
1.15.3 Confounding Issues 126
1.15.4 Exercise Physiology of “Positional Restraint” and “Restraint
Asphyxia” 126
1.15.5 Neurochemistry of Excited Delirium Syndrome 128
1.15.6 Autopsy Findings 131
1.15.7 Toxicology of Excited Delirium Syndrome 132
1.15.8 Potential Biomarkers 132
1.15.8.1 Neuropeptides 132
1.15.8.2 Heat Shock Proteins 133
1.15.9 Cause of Death Determination in ExDS 134
1.16 Cocaine-Associated Pulmonary Disease 134
1.16.1 Barotrauma 136
1.16.2 Parenchymal Disease 139
1.16.3 Vascular Adaptations 143
1.17 Neurologic Disorders: Introduction 144
1.17.1 Molecular Basis of Cocaine Neurotoxicity 144

1.17.2 Psychiatric Syndromes 145
1.17.3 Cognitive Impairment 146
1.17.4 Ischemic Stroke 147
1.17.5 Cerebral Vasculitis 149
1.17.6 Subarachnoid and Intraventricular Hemorrhage 150
1.17.7 Seizures 152
1.17.8 Movement Disorders 153
1.17.9 Blood–Brain Barrier Alterations 153
1.18 Renal Disease 154
1.18.1 Cocaine-Related Kidney Disease 154
1.19 Hematologic Abnormalities 158
1.19.1 hrombocytopenic Purpura 158
1.19.2 hrombosis 159
x Contents
1.19.3 Erythrocytosis 159
1.19.4 Methemoglobinemia 160
1.20 Hormonal Alterations 160
1.20.1 Overview 160
1.20.2 Prolactin 161
1.20.3 Sex Hormones 161
1.21 Immune System Abnormalities 162
1.22 Gastrointestinal Disorders 163
1.22.1 Introduction 163
1.22.2 “Body Packing” 163
1.22.3 Ischemic Bowel and Stomach Injuries 164
1.22.4 Hepatic Disease 165
1.23 Analytic and Forensic Toxicology 168
1.23.1 Bioanalytic Considerations 168
1.23.2 Preferred Analytic Methods 169
1.23.2.1 Screening Methods 169
1.23.2.2 Conirmatory Methods 170
1.23.3 Tissue Concentrations, Analytical Considerations 170
1.23.3.1 Heart 170
1.23.3.2 Kidneys 171
1.24 Pregnancy Interactions 171
1.25 When Is Cocaine the Cause of Death? 173
References 176
2
Natural Stimulants 225
2.1 Absinthe 226
2.1.1 Incidence and Epidemiology 226
2.1.2 History 227
2.1.3 Manufacture 230
2.1.4 Routes of Administration 230
2.1.5 General Pharmacology 231
2.1.6 Tissue Concentrations 232
2.1.7 Toxicity by Organ System 232
2.2 Cafeine 233
2.2.1 Incidence 233
2.2.2 Epidemiology 234
2.2.3 History 234
2.2.4 Chemical Constants and Physiochemical Properties 237
2.2.5 Sources 237
2.2.6 Routes of Administration 239
2.2.7 Metabolism 239
2.2.8 Mechanisms of Action 240
2.2.9 Pharmacokinetics 242
2.2.10 Tissue Concentrations 243
2.2.11 Toxicity by Organ System 244