The forensic pharmacology of drugs of abuse

Foreword xii 
Preface xiii 
Acknowledgements xiv 
Abbreviations xv 
Definitions and glossary xvi 
I INTRODUCTORY ASPECTS OF DRUG ACTIONS I 
1.1 General introduction 2 
Use of drugs in the general community 2 
Prevalence of drugs in sudden death 2 
Manufacture and production of psychoactive drugs 3 
Psychoactive substances 4 
Alcohol 5 
Opioids 6Cannabis 6 
The sedatives and hypnotics 6 
Amphetamines, cocaine and other abused stimulants 7 
Other drugs of abuse 7 
Focus of this book 7 
1.2 Specimens and specimen collection procedures 9 
Specimens and their relative merits 9 
1.3 Analysis and measurement 17 
Cut-off levels and approved assays 17 
Validation and uncertainty 18 
Quality assurance 21 
1.4 Pharmacokinetics and duration of action 22 
Absorption and bioavailability 22 
Volume of distribution 23 
Clearance 25 
Half-life 25 
Metabolism 27 
Excretion 28 
Duration of action 29 
Metabolic interactions 3 I 
 
Pharmacokinetics in the elderly 32Pharmacokinetics in disease states 33 
Pharmacokinetics in obesity 33 
Pharmacokinetics in children 34 
Effect of blood loss and blood replacements 34 
1.5 Tolerance and dependence 36 
Defining drug dependency 36 
Tolerance 37 
Side effects and adverse reactions 37 
1.6 Toxicology 38 
Chemical instability 38 
Metabolic changes 38 
Postmortem redistribution 39 
Other processes 41 
Interpretation of toxicological information 41 
References for Section I 43 
2 STIMULANTS 49 
Foreword 50 
2.1 Classification and sources of stimulants 52 
Historical aspects 52 
Structures and sources of amphetamine-like stimulants 54 
Synopsis 59 
2.2 Pharmacokinetics and duration of action 60Metabolism 60 
Absorption and half-life 62 
Half-life 67 
Excretion and urine detection times 68 
Synopsis 69 
2.3 Mechanisms of action 71 
Amphetamines 71 
Cocaine 72 
Synopsis 72 
2.4 Pharmacological actions and therapeutics 74 
Amphetamines and related stimulants 74 
Cocaine 76 
Medical uses of stimulants 77 
Synopsis 77 
2.5 Adverse reactions, tolerance and dependence 79 
Abuse potential 79 
Adverse reactions 79 
Tolerance 80
Dependence and abstinence 81
Synopsis 82
2.6 Toxicology 83
Prevalence in forensic cases 83
Toxicology and pathology of stimulants 84
Toxicology and pathology of cocaine 89
Redistribution 91
2.7 Tissue concentrations 91
Synopsis 91
Case reports 93
Case Report 2.1 Amphetamine- and cocaine induced self-defence 93
Case Report 2.2 Speed and violence 93
Case Report 2.3 Rave to the grave 94
Case Report 2.4 Amphetamine-induced fatigue 94
Case Report 2.5 Cocaine intoxication leading to death 94
Case Report 2.6 Detection of amphetamine use at the workplace 95
References for Section 2 96
Benzodiazepines and other related drugs 103
Foreward 104

3.1 Source and structures 105
Structural features of benzodiazepines 105
Classification of benzodiazepines 110
Other related anxiolytics and hypnotics 111
Synopsis 114
3.2 
Pharmacokinetics and duration of action 116
Absorption and bioavailability 116
Routes of metabolism 119
Enzyme systems involved in metabolism 121
Excretion 121
Duration of action 123
Metabolic interactions 124
Pharmacokinetics in various physiological states 126 
Synopsis 129
3.3 
Mechanisms of action 130
Benzodiazepines 130
Barbiturates 132
Zolpidem and the imidazopyridines 132
Redistribution 91
3.4 Pharmacological actions and therapeutics * 34
Indications for benzodiazepines * 34 
Other hypnotics and sedatives * 36 
Benzodiazepines in the elderly 137 
Non-medical uses of sedatives * 38 
Therapeutics *38 
Synopsis *40 
3.5 Adverse reactions and tolerance *41 
Benzodiazepines *41 
Effect on memory and cognitive functions 142 
Other anxiolytics *46 
Effect on driving 146 
Drug interactions 147 
Tolerance and dependence 147 
Barbiturates 149 
Buspirone, zolpidem and zopiclone 149 
Synopsis 149 
3.6 Toxicology 151 
Use of benzodiazepines by drug users 15 I 
Toxic reactions to benzodiazepines 15 IToxic reactions to barbiturates 157 
Toxic reactions to zolpidem 157 
Toxic reactions to zopiclone 159 
Tissue distribution of sedatives I 59 
Synopsis 161 
3.7 Case reports 163 
Case Report 3.1 Negative drug result 163 
Case Report 3.2 Paradoxical reaction to benzodiazepines 163 
Case Report 3.3 Behavioural aggression 164 
Case Report 3.4 Sexual and aggressive fantasies 164 
Case Report 3.5 Sexual disinhibition due to benzodiazepines 165 
Case Report 3.6 Death due to flunitrazepam 165 
References for Section 3 166 
4 CANNABIS 177 
Foreword 178 
4.1 Source and structures of cannabinoids 179 
Historical aspects and synonyms 179 
Cannabis species 179 
Active constituents of Cannabis sativa \ 80 
Cannabis products lg| 
Other substances with THC-like activity 181 
Synopsis | 824.2 Pharmacokinetics and duration of action 183 
Absorption and bioavailability 183 
Prediction of time of administration 186 
Metabolism and biological activity of metabolites 186 
Excretion Igg 
Duration of action I g 9 
Alternative sources of cannabinoids 194 
Nabilone: a synthetic cannabinoid 195 
Synopsis 195 
4.3 Mechanisms of action 197 
4.4 Pharmacological actions and therapeutics 198 
Acute physiological effects |98 
Acute behavioural changes 198 
Chronic and adverse health effects 200 
Medical uses 201 
Synopsis 202 
4.5 Tolerance and dependence 203 
Tolerance 203 
Dependence 203 
Synopsis 204 
4.6 Toxicology 205 
Prevalence of THC in forensic cases 205Contribution of cannabis use to death 205 
Contribution to motor vehicle accidents 206 
Impairing blood concentrations of THC 207 
Synopsis 207 
4.7 Case reports 209 
Case Report 4.1 Proof of cannabis use 209 
Case Report 4.2 THC back calculation 209 
Case Report 4.3 Cannabis intoxication while driving - I 210Case Report 4.4 Cannabis intoxication while driving - 2 211References for Section 4 212 
5 OPIOIDS 219 
Foreword 220
5.1 Source and structures 221 
Sources of opioids 221 
Structural features 222 
Synopsis 224 
5.2 Pharmacokinetics and duration of action 225 
Absorption and bioavailability 225 
Pharmacokinetics in various physiological states 230 
Pharmacokinetic profiles of selected opioids 23 ISynopsis 237 
5.3 Mechanisms of action 238 
Mu-opioid receptor 238 
Delta-opioid receptor 238 
Kappa-opioid receptor 239 
Other actions 239 
Synopsis 239 
5.4 Pharmacological actions and therapeutics 241 
Uses of opioids 241 
Side effects of opioids 242 
Non-medical uses of opioids 244 
Therapeutics 244 
Synopsis 245 
5.5 Adverse reactions and dependence 246 
Dependence and tolerance 246 
Withdrawal symptoms 246 
Important drug interactions 247 
Synopsis 248 
5.6 Toxicology 249 
Heroin and morphine 249 
Other opioids 253 
Toxic concentrations of opioids 258Distinguishing source of opioid from urine profile 258 
Ingestion of poppy seeds and morphine excretion 259 
Synopsis 260 
5.7 Case reports 261 
Case Report 5.1 Occupational drug testing 261 
Case Report 5.2 Acute heroin death 261 
Case Report 5.3 Delayed heroin death 262 
Case Report 5.4 Methadone death 263 
265 
References for Section 5 
6 ETHANOL 273 
Foreword 274 
6.1 Types and sources of alcohol 275 
Structures of alcohols 275 
Physical properties of alcohols 275 
Historical aspects and source 276 
Alcoholic content of beverages 276 
Alcoholic content of commercial products 277 
Synopsis 277 
6.2 Pharmacokinetics, metabolism and duration of action 278 
Absorption 278 
Metabolism 281Excretion and detection times 284 
Drugs affecting absorption and elimination 285 
Markers of alcohol consumption 286 
Duration of action 287 
Effects of alcohol on drug pharmacokinetics 287 
Synopsis 289 
6.3 Mechanisms of action 290 
CNS mechanisms 290 
Peripheral mechanisms 291 
Synopsis 291 
6.4 Pharmacological actions and therapeutics 292 
CNS effects 292 
Cardiovascular system 293 
Liver and gastrointestinal system 293 
Other effects 294 
Therapeutic uses of ethanol 295 
Synopsis 296 
6.5 Adverse reactions, tolerance and dependence 297 
Abuse potential 297 
Adverse reactions 297 
Tolerance 298 
Dependence and abstinence 298Synopsis 299 
6.6 Toxicology 300 
Prevalence in forensic cases 300 
Fermentation 301 
Collection artefacts 301 
Contents 
Redistribution and diffusion 301 
Tissue concentrations 302 
Toxicology and pathology of ethanol 305 
Adverse drug interactions 307 
Synopsis 307 
6.7 Case reports 309 
Case Report 6 .1 Alcohol read-back I 309 
Case Report 6.2 Alcohol read-back 2 310 
Case Report 6.3 Alcohol and homicide 3 I I 
Case Report 6.4 Alcohol and putrefaction 3 I I 
References for Section 6 313 
7 OTHER DRUGS OF ABUSE 321 
Foreword 322 
7.1 LSD 323 
Source and structures 323 
Tissue concentrations, metabolism and excretion 323Mechanism of action 324 
Pharmacological actions and adverse reactions 324 
Toxicity 324 
7.2 Phencyclidine and related hallucinogens 326 
Mechanism of action 326 
Pharmacological actions and adverse reactions 327 
Tissue concentrations, metabolism and excretion 327 
Toxicity 328 
7.3 Gamma-hydroxy butyrate 329 
Tissue concentrations, metabolism and excretion 329 
Pharmacological actions and adverse reactions 329 
Mechanism of action 330 
Toxicity 330 
7.4 Volatile substances 331 
Types of volatile substances 33 | 
Tissue concentration, metabolism and excretion 332 
Mechanism and frequency of use 332 
Pharmacological actions and adverse effects 332 
7.5 Case reports 334 
Case Report 7.1 PCP and violent behaviour leading to death 334 
Contents 
Case Report 7.2 Driving while intoxicated with GHB 334Case Report 7.3 GHB withdrawal 334 
Case Report 7.4 GHB intoxication 335 
References for Section 7 335 
8 CLINICAL FORENSIC ASPECTS OF DRUG USE 339 
Foreword 340 
8.1 Reasons for a forensic medical examination 341 
8.2 Health status of drug users 344 
8.3 Principles of an examination scheme for drug-affected persons 345 
Obtaining a history 345 
The examination 345 
8.4 Clinical forensic opinions 348 
8.5 Common drug effects seen in clinical medicine 349 
Stimulants 349 
Benzodiazepines 351 
Cannabis 353 
Opioids 354 
Alcohol 357 
8.6 Case reports 360 
Case Report 8 .1 Fitness for interview 360 
Case Report 8.2 Drug-affected driving and doctor shopping 360 
Case Report 8.3 Benzodiazepine overdose 362 
Case Report 8.4 Methadone toxicity 363Case Report 8.5 Alcohol intoxication 364 
References for Section 8 365 
APPENDIX - MONOGRAPHS OF SELECTED DRUGS 367 
Explanations to monographs 368 
Stimulants 369 
Benzodiazepines 382 
Other sedatives and anxiolytics 406 
Opioids and related drugs 413 
Other monographs 435 
References for Appendix 442 
Index 451