Steven B. Karch0849326370, 9780849326370
Table of contents :
Header……Page 1
PREFACE……Page 4
THE EDITOR……Page 6
CONTRIBUTORS……Page 7
ACKNOWLEDGMENTS……Page 12
TABLE OF CONTENTS……Page 13
CHAPTER 1: CRIMINALISTICS—INTRODUCTION TO CONTROLLED SUBSTANCES……Page 16
1.1 DEFINITION AND SCHEDULING OF CONTROLLED SUBSTANCES……Page 17
1.2 SCHEDULING OF CONTROLLED SUBSTANCES……Page 18
1.3 CONTROLLED SUBSTANCE ANALOGUE ENFORCEMENT ACT OF 1986……Page 19
1.4.1 HERION……Page 20
1.4.1.1 Heroin Sources by Region……Page 21
1.4.1.2 Isolation of Morphine and Heroin Production……Page 22
1.4.2 COCAINE……Page 24
1.4.2.1 Sources of Cocaine……Page 25
1.4.2.3 Isolation and Purification……Page 26
1.4.2.5 Other Coca Alkaloids……Page 28
REFERENCES……Page 29
1.4.3.1 History and Terminology……Page 30
1.4.3.2 Laboratory Analysis……Page 31
1.4.4 PEYOTE……Page 32
1.4.5 PSILOCYBIN MUSHROOMS……Page 33
REFERENCES……Page 34
1.4.6 LYSERGIC ACID DIETHYLAMIDE (LSD)……Page 35
1.4.7 PHENCYCLIDINE (PCP)……Page 36
1.4.8 FENTANYL……Page 37
1.4.9 PHENETHYLAMINES……Page 38
1.4.11 CATHA EDULIS (KHAT)……Page 43
REFERENCES……Page 44
Control of Steroids……Page 45
1.4.12.2 Structure Activity Relationship……Page 47
1.4.12.3 Forensic Analysis……Page 48
REFERENCES……Page 50
1.5.2 OTHER CENTRAL NERVOUS SYSTEM DEPRESSANTS……Page 51
1.5.3 NARCOTIC ANALGESICS……Page 52
REFERENCE……Page 53
1.6.2 TABLET MARKINGS AND CAPSULE IMPRINTS……Page 54
1.6.3 BLOTTER PAPER LSD……Page 56
1.7.1 SCREENING TESTS……Page 57
1.7.1.3 Thin Layer Chromatography……Page 58
1.7.2.2 Gas Chromatography……Page 59
1.7.2.3 High Performance Liquid Chromatography (HPLC)……Page 60
1.7.2.5 Infrared Spectrophotometry (IR)……Page 61
1.7.2.6 Gas Chromatography/Mass Spectroscopy (GC/MS)……Page 62
1.7.2.7 Nuclear Magnetic Resonance (NMR) Spectroscopy……Page 64
1.7.3.1 Identifying and Quantitating Controlled Substances……Page 65
1.7.3.2 Identifying Adulterants and Diluents……Page 67
1.7.3.3 Quantitating Controlled Substances……Page 68
1.7.3.4 Reference Standards……Page 70
1.8.1 DETERMINING COMMONALITY OF SOURCE……Page 71
1.8.3 COMPARING COCAINE EXHIBITS……Page 72
1.9 CLANDESTINE LABORATORIES……Page 73
1.9.1 SAFETY CONCERNS……Page 74
1.9.3.1 Generalized List by Category of Physiological Effects and Medical Uses of Controlled Substances……Page 76
1.9.3.2 Listing of Controlled Substances by Schedule Number……Page 81
CHAPTER 2: PATHOLOGY OF DRUG ABUSE……Page 91
2.1.1 INVESTIGATING THE SCENE OF DEATH……Page 93
2.1.1.2 Body Packers……Page 95
2.1.2 GENERAL AUTOPSY CONSIDERATIONS……Page 96
REFERENCES……Page 99
2.2.1.1 Removal of the Heart……Page 100
2.2.1.2 Examination of Coronary Arteries……Page 101
2.2.1.3 Examination of Bypass Grafts……Page 103
2.2.1.4. Examination of the Myocardium in Ischemic Heart Disease……Page 104
2.2.1.6 Examination of the Heart Valves……Page 106
2.2.1.7 Prosthetic Heart Valves……Page 107
2.2.1.8 Examination of the Aorta……Page 109
2.2.1.9 EXAMINATION OF THE CONDUCTION SYSTEM……Page 111
2.2.1.10 Evaluating Cardiac Hypertrophy……Page 112
REFERENCES……Page 114
2.2.2.1 Epidemology Considerations……Page 115
2.2.2.2 Myocardial Hypertrophy……Page 116
2.2.2.3 Myocardial Disease in Stimulant Abusers……Page 117
2.2.2.4 Myocardial Disease in Opiate Abusers……Page 119
REFERENCES……Page 120
2.2.3.1 Incidence and Clinical Profile……Page 123
2.2.3.2 Postmortem Appearance……Page 124
REFERENCES……Page 126
2.2.4 VASCULAR EFFECTS OF SUBSTANCE ABUSE*……Page 127
2.2.4.1 Cocaine……Page 130
2.2.4.1.2 Thrombosis……Page 131
2.2.4.1.4 Endothelial Dysfunction……Page 132
2.2.4.1.5 Hemodynamic Alterations……Page 133
2.2.4.2 Methamphetamine……Page 134
2.2.4.5 Solvents (“Glue Sniffing”)……Page 135
2.2.4.6.1 Ergot Alkaloids……Page 136
2.2.4.6.4 L-Tryptophan……Page 137
REFERENCES……Page 138
2.3.1 PATHOLOGY ENCOUNTERED IN “CRACK” SMOKERS……Page 143
2.3.2 ALTERATIONS ASSOCIATED WITH INTRAVENOUS DRUG ABUSE……Page 145
2.3.3 ASPIRATION PNEUMONIA……Page 146
REFERENCES……Page 148
2.4.1 ALCOHOL RELATED DISORDERS……Page 149
2.4.2.1 Excited Delirium……Page 151
2.4.2.2 Cerebral Hemorrhage……Page 152
2.4.2.4 Seizures……Page 156
2.4.2.6 Anoxic Ischemic Encephalopathy……Page 158
2.4.2.7 Drug-Associated Central Nervous System Infections……Page 159
REFERENCES……Page 160
2.5 MISCELLANEOUS COMPLICATIONS……Page 163
REFERENCES……Page 164
CHAPTER 3: PHARMACOKINETICS: DRUG ABSORPTION, DISTRIBUTION, AND ELIMINATION……Page 165
3.1.1 TRANSFER ACROSS BIOLOGICAL MEMBRANES……Page 167
3.1.1.1.1 Gastrointestinal……Page 169
3.1.1.1.4 Parenteral Injection……Page 170
3.1.1.2.1 Binding to Tissue Constituents……Page 171
3.1.2 BIOTRANSFORMATION……Page 172
3.1.2.2 Phase II Enzymes……Page 173
3.1.3 ELIMINATION……Page 174
3.1.4.1 Clearance……Page 175
3.1.4.3 Bioavailability……Page 176
3.1.5.1 Loading Doses……Page 177
3.1.6.1.1 Time Delays……Page 178
3.2.1 COMPARTMENTAL MODELING……Page 179
3.2.1.3 Elimination Kinetics……Page 180
3.3 PHARMACOKINETIC-PHARMACODYNAMIC CORRELATIONS……Page 183
3.5 FACTORS AFFECTING PHARMACOKINETIC PARAMETERS……Page 184
3.5.2 SEX DIFFERENCES……Page 185
3.5.4 DRUG AND DISEASE INTERACTIONS……Page 186
REFERENCES……Page 187
3.6.1.1 Absorption……Page 188
3.6.1.3 Metabolism and Excretion……Page 189
3.6.2.2 Metabolism and Excretion……Page 190
3.6.4 3,4-METHYLENEDIOXYMETHAMPHETAMINE……Page 191
3.6.5 BARBITURATES……Page 192
3.6.5.2 Absorption……Page 193
3.6.5.4 Metabolism and Elimination……Page 194
3.6.8 BENZODIAZEPINES……Page 195
3.6.8.3 Distribution……Page 196
3.6.8.4 Metabolism and Elimination……Page 197
3.6.9 COCAINE……Page 198
3.6.9.2 Absorption……Page 199
3.6.9.4 Metabolism……Page 200
REFERENCES……Page 201
3.6.10.2 Absorption……Page 202
REFERENCES……Page 203
3.6.11.2 Absorption……Page 204
3.6.11.3 Distribution……Page 205
3.6.11.4 Metabolism and Excretion……Page 206
3.6.12 OPIOIDS……Page 207
3.6.12.1.2 Absorption……Page 208
3.6.12.1.4 Metabolism and Excretion……Page 209
3.6.12.2 Heroin……Page 210
3.6.12.3 Methadone……Page 211
REFERENCES……Page 212
3.6.13.1 Pharmacology……Page 213
3.6.13.4 Metabolism and Excretion……Page 214
REFERENCES……Page 215
CHAPTER 4: PHARMACODYNAMICS……Page 216
4.1.1 EFFECTS OF DRUGS ON PERFORMANCE……Page 219
4.1.1.1.3 Attentional Abilities……Page 220
4.1.1.1.5 Summary……Page 221
4.1.1.2.2 Motor Abilities……Page 222
4.1.1.2.3 Attentional Abilities……Page 223
4.1.1.2.5 Summary……Page 224
4.1.1.3.1 Sensory Abilities……Page 225
4.1.1.3.3 Attentional Abilities……Page 226
4.1.1.3.4 Cognitive Abilities……Page 228
4.1.1.4 Opioid Analgesics and Anesthetics……Page 229
4.1.1.4.2 Motor Abilities……Page 230
4.1.1.4.4 Cognitive Abilities……Page 231
4.1.1.5 Marijuana……Page 232
4.1.1.5.3 Attentional Abilities……Page 233
4.1.1.5.5 Summary……Page 234
4.1.2.1.1 Lack of a Useful Performance Assessment Battery……Page 235
4.1.2.2.1 Criteria for Usefulness of a Performance Test……Page 236
4.1.2.2.3 Complete Drug Effect Profiles……Page 237
REFERENCES……Page 238
4.2 PERFORMANCE MEASURES OF BEHAVIORAL IMPAIRMENT IN APPLIED SETTINGS……Page 248
4.2.1 ISSUES IN THE SELECTION AND IMPLEMENTATION OF PERFORMANCE TESTING TECHNOLOGIES……Page 250
4.2.1.1 Selecting a Performance Testing System……Page 251
4.2.1.1.2 Reliability and Validity……Page 252
4.2.1.1.3 Evaluation Norms……Page 253
4.2.1.1.4 Administrative Interface……Page 254
4.2.1.2.1 Computer……Page 255
4.2.1.2.3 Software……Page 256
4.2.2. TEST IMPLEMENTATION……Page 257
4.2.2.4 User Acceptance……Page 258
4.2.3. APPLICATIONS OF PERFORMANCE TESTING TECHNOLOGIES……Page 259
4.2.3.1.1 Background……Page 260
4.2.3.1.2.1 Research Methodology……Page 261
4.2.3.1.2.3 DEC Evaluation……Page 262
4.2.3.1.2.5 Conclusions……Page 264
4.2.3.2.2.1 Unified Tri-Service Cognitive Performance Assessment Battery……Page 265
4.2.3.2.2.2 Walter Reed Army Institute Performance Assessment Battery……Page 266
4.2.3.2.2.3 Naval Medical Research Institute Performance Assessment Battery……Page 267
4.2.3.2.2.5 Automated Neuropsychological Assessment Metrics……Page 268
4.2.3.2.2.6 Neurobehavioral Evaluation System 2……Page 269
4.2.3.2.2.8 Memory Assessment Clinics Battery……Page 270
4.2.3.2.2.9 Synwork……Page 271
4.2.3.3.2 Performance Tests in Applied Settings……Page 272
4.2.3.3.2.1 Truck Operator Proficiency System/ReadyShift……Page 273
4.2.3.3.2.4 Performance-on-Line, Profile Associates……Page 274
REFERENCES……Page 275
4.3.1.2 Instrumentation……Page 279
4.3.1.3 Light Reflex……Page 280
4.3.2.1 Methods……Page 281
4.3.2.2.1 Pupil Diameter……Page 282
4.3.2.2.6 Performance Measures (Figure 4.3.2.2.6)……Page 283
4.3.3.7 Nicotine……Page 285
4.3.5.3 Effect of Fatigue, Disease, and Legal Drugs……Page 286
REFERENCES……Page 287
4.4.1 FACTORS THAT AFFECT ABUSE LIABILITY……Page 289
4.4.2.1.1 Psychomotor Stimulants……Page 290
4.4.2.1.3 Sedatives……Page 291
4.4.2.1.5 Hallucinogens……Page 292
4.4.2.2 Structure Activity Relationships……Page 293
4.4.2.3 Pharmacokinetics……Page 294
4.4.2.4 Physical Properties……Page 295
4.4.3.1 Self-Administration……Page 296
4.4.3.2 Drug Discrimination……Page 298
4.4.3.3 Subjective Effects……Page 301
4.4.3.4 Physical Dependence Capacity……Page 305
4.4.4 PREDICTIVE VALUE……Page 307
REFERENCES……Page 310
CHAPTER 5: ALCOHOL……Page 320
5.1.1.1 Motor Control and Cognitive Functioning……Page 322
5.1.1.1.2 Dual-Task Performance……Page 323
5.1.1.2 Speech……Page 324
5.1.1.3.1 Positional Alcohol Nystagmus (PAN)……Page 325
5.1.1.3.2 Horizontal Gaze Nystagmus (HGN)……Page 326
5.1.2 TIME OF INGESTION……Page 327
5.1.2.2 Acute Tolerance……Page 328
5.1.2.3 Hangover……Page 329
5.1.3.1 Ideal Characteristics of Impairment Tests……Page 330
5.1.3.1.3 Sensitivity……Page 331
5.1.3.2 Characteristics of Existing Field Sobriety Tests……Page 332
5.1.4 CONCLUSIONS……Page 334
REFERENCES……Page 335
5.2 MEASURING BLOOD-ALCOHOL CONCENTRATION FOR CLINICAL AND FORENSIC PURPOSES……Page 340
5.2.1 UNITS OF CONCENTRATION — PLASMA/SERUM VS. WHOLE BLOOD……Page 341
5.2.2.2 Enzymatic Methods……Page 343
5.2.2.3 Gas Chromatographic Methods……Page 344
5.2.2.4 Other Methods……Page 347
5.2.3 BREATH ALCOHOL ANALYSIS……Page 348
5.2.4 QUALITY ASSURANCE ASPECTS OF ALCOHOL ANALYSIS……Page 350
5.2.4.2 Analytical Factors……Page 351
5.2.5 FATE OF ALCOHOL IN THE BODY……Page 352
5.2.6.1 Widmark Model……Page 355
5.2.6.2 Michaelis-Menten Model……Page 357
5.2.6.3 First-Pass Metabolism and Gastric Alcohol Dehydrogenase……Page 358
5.2.6.4 Food and Pharmacokinetics of Ethanol……Page 359
5.2.7 CONCLUSIONS……Page 360
REFERENCES……Page 361
5.3 MEASURING ALCOHOL POSTMORTEM……Page 369
5.3.1.2 Water Content and Ethanol Content……Page 370
5.3.2.3 Effects of Tolerance……Page 371
5.3.2.4 Interaction of Alcohol with Other Drugs……Page 372
5.3.3.1 Relationship to Blood Alcohol Concentrations……Page 373
5.3.4 URINARY ALCOHOL……Page 374
5.3.5.2 Postmortem Diffusion……Page 375
5.3.6 ALCOHOL SYNTHESIS POSTMORTEM……Page 376
5.3.6.2 Observed Ranges……Page 377
5.3.6.4 Importance of Corroborative Analysis……Page 378
5.3.7 SEQUESTERED HEMATOMAS……Page 379
5.3.8 METHANOL……Page 380
5.3.8.2 Endogenous Methanol Production……Page 381
5.3.10 OTHER BIOLOGICAL SAMPLES……Page 382
REFERENCES……Page 383
5.4 BIOCHEMICAL TESTS FOR ACUTE AND CHRONIC ALCOHOL INGESTION……Page 387
5.4.2.1 Measuring Ethanol in Body Fluids and Breath……Page 389
5.4.2.2 Metabolites of Ethanol Oxidation……Page 391
5.4.2.3 Measuring Methanol in Body Fluids……Page 392
5.4.2.4 Metabolites of Serotonin……Page 394
5.4.3.1 g-Glutamyl Transferase (GGT)……Page 395
5.4.3.4 Carbohydrate-Deficient Transferrin (CDT)……Page 396
5.4.3.6 Other Potential Tests of Chronic Ingestion……Page 397
5.4.4.1 Single Tests or Test Combinations?……Page 398
5.4.5 TRAIT MARKERS OF ALCOHOL DEPENDENCE……Page 399
5.4.6 CONCLUSIONS……Page 400
REFERENCES……Page 401
CHAPTER 6: NEUROCHEMISTRY OF DRUG ABUSE……Page 408
6.1.1 DOPAMINE UPTAKE……Page 410
6.1.2.1 Cocaine……Page 411
6.1.2.2 Amphetamine……Page 412
6.1.2.4 Phencyclidine (PCP)……Page 413
6.1.2.5 Marijuana……Page 414
6.1.2.7 Nicotine……Page 415
6.1.3 CONCLUSIONS……Page 416
REFERENCES……Page 417
6.2 NEUROPSYCHIATRIC CONSEQUENCES OF CHRONIC COCAINE ABUSE……Page 425
6.2.1 DIFFERENTIAL DIAGNOSIS OF PSYCHOTIC DISORDERS……Page 426
6.2.2 COCAINE DELIRIUM……Page 427
6.2.3 ALTERED DOPAMINERGIC TRANSMISSION AND THE SYNDROME OF COCAINE DELIRIUM……Page 429
REFERENCES……Page 431
6.3 NEUROCHEMICAL ADAPTATIONS AND COCAINE DEPENDENCE……Page 433
6.3.2.1 Regulation of the DA Transporter By Cocaine……Page 434
6.3.2.4 Cocaine Vaccines……Page 436
6.3.3.1 Cocaine-Induced D1 Receptor Adaptations……Page 437
6.3.3.3 Cocaine-Induced Adaptations in D3 Receptors……Page 438
6.3.3.4 DA Receptors as Targets for Cocaine Pharmacotherapies……Page 439
6.3.4 KAPPA OPIOIDERGIC RECEPTORS……Page 440
6.3.4.1 Regulation of k Receptors By Cocaine……Page 441
6.3.5 SEROTONIN TRANSPORTER AND COCAINE DEPENDENCE……Page 442
6.3.6 GLUTAMATE RECEPTORS AND COCAINE DEPENDENCE……Page 443
6.3.7.1 Phentermine/Fenfluramine: The “Phen-Fen” Protocol……Page 444
6.3.7.2 Ibogaine: The Rainforest Alkaloid……Page 445
REFERENCES……Page 446
ACKNOWLEDGMENT……Page 454
6.4.1 COMPETING THEORIES……Page 455
6.4.2 RELAPSE IN AN ANIMAL MODEL OF DRUG-SEEKING BEHAVIOR……Page 456
6.4.3 NEUROCHEMICAL SUBSTRATES OF RELAPSE……Page 458
6.4.4 NEUROPHARMACOLOGICAL SUBSTRATES OF RELAPSE……Page 461
6.4.5 INTRACELLULAR SUBSTRATES OF RELAPSE……Page 463
6.4.6.1 Adaptations in Dopamine Neurons……Page 466
6.4.7 CONCLUSIONS……Page 468
REFERENCES……Page 469
6.5 SEROTONERGIC DYSFUNCTION DURING COCAINE WITHDRAWAL: IMPLICATIONS FOR COCAINE-INDUCED DEPRESSION……Page 476
6.5.1.1 Anatomy of Brain 5-HT Systems……Page 477
6.5.2 ACUTE EFFECTS OF COCAINE ON 5-HT NEURONS……Page 478
6.5.3.1 The Neuroendocrine Challenge Approach……Page 479
6.5.3.2 Changes in Presynaptic 5-HT Transmission……Page 480
6.5.3.3 Changes in Postsynaptic 5-HT Receptor Sensitivity……Page 481
6.5.3.4 Glucocorticoid – 5-HT Relationships……Page 483
6.5.4 COCAINE WITHDRAWAL IN HUMANS INDUCES DEPRESSIVE-LIKE SYMPTOMS……Page 484
6.5.5.1 Changes in Presynaptic Transmission……Page 485
6.5.5.2 Changes in Postsynaptic 5-HT Receptor Sensitivity……Page 486
6.5.5.3 Glucocorticoid – 5-HT Relationships……Page 487
6.5.6 CONCLUDING REMARKS……Page 488
REFERENCES……Page 489
6.6.1 TERMINOLOGY……Page 498
6.6.2 HISTORY……Page 499
6.6.3.2 Pharmacological……Page 500
6.6.4.1 Indolealkylamines……Page 501
6.6.4.1.2 DMT……Page 503
6.6.4.1.5 LSD and Other Psychotropic Ergotamines……Page 504
6.6.5.2 Other Psychotropic Phenethylamines……Page 505
6.6.5.2.1 DOB……Page 506
6.6.6 SUMMARY AND CONCLUSIONS……Page 507
REFERENCES……Page 508
CHAPTER 7: ADDICTION MEDICINE……Page 512
7.1.1 UNDERSTANDING THE NATURE OF DEPENDENCE……Page 513
7.1.2.1 Potency of Psychactive Effect……Page 515
7.1.2.3 Plasticity……Page 516
7.1.3 UNDERSTANDING THE IMPORTANCE OF MOTIVATION……Page 517
7.1.5 GENERAL PRECAUTIONS……Page 518
7.2.1 OPIATE SPECIFIC PRESCRIBING……Page 519
7.2.1.2 Treatment Compliance……Page 520
7.2.1.3 Therapeutic Drug Monitoring for Methadone……Page 521
7.2.1.4 Indications for Plasma Methadone Monitoring……Page 522
7.2.1.6 Buprenorphine Maintenance Prescribing……Page 523
7.2.4 OUTCOMES FOR SUBSTITUTE PRESCRIBING……Page 524
7.3.1 UNDERSTANDING WITHDRAWAL SYNDROMES……Page 525
7.3.1.1 Detoxification……Page 526
7.3.2 OPIATE SPECIFIC WITHDRAWAL SYNDROME……Page 527
7.3.2.2 Detoxification Using Buprenorphine……Page 528
7.3.2.3 Detoxification Using Adrenergic Agonists……Page 529
7.3.3 STIMULANTS SPECIFIC WITHDRAWAL SYNDROME……Page 530
7.3.4 HYPNOTIC AND SEDATIVE WITHDRAWAL SYNDROME……Page 532
7.3.4.1 Management of Withdrawal……Page 533
7.4.1.1 Opiate Antagonists……Page 534
7.4.2 STIMULANT SPECIFIC PRESCRIBING……Page 535
Dopamine Agonists……Page 536
7.4.2.2 Clinical Approach, Tricyclic Antidepressants and Anti-Sensitizing Agents……Page 537
7.4.3 NEW APPROACHES……Page 538
7.5.1 UNDERSTANDING COMORBIDITY……Page 539
7.5.2 MAKING PRESCRIBING DECISIONS……Page 540
7.6.1 HEAT AND DRUG STABILITY……Page 542
7.6.2.4 Costs……Page 543
REFERENCES……Page 544
CHAPTER 8: MEDICAL COMPLICATIONS OF DRUG ABUSE……Page 552
8.1 DRUG-RELATED SYNDROMES……Page 555
8.1.1 SYNDROMES ASSOCIATED WITH STIMULANT ABUSE……Page 556
8.1.1.1.1 Central Nervous System……Page 557
8.1.1.1.2 Cardiovascular System……Page 559
8.1.1.2.1 Ephedrine……Page 560
8.1.1.3.1 Amphetamine……Page 561
8.1.1.3.4 Phenylpropanolamine……Page 562
8.1.2.1.1 Mescaline……Page 563
8.1.2.1.7 MDMA (3,4-methylenedioxymethamphetamine)……Page 564
8.1.2.2 Lysergic Acid Diethylamide (LSD)……Page 565
8.1.2.3 Disassociative Anesthetics (Phencyclidine)……Page 566
8.1.4 OPIATE DRUGS……Page 567
8.1.4.1.2 Gastrointestinal Effects……Page 568
8.1.4.2.1 Morphine……Page 569
8.1.4.2.6 Fentanyl……Page 570
8.1.4.3 Opiate Withdrawal……Page 571
8.1.5.1 Benzodiazepines……Page 572
8.1.5.2 Barbiturates……Page 573
8.1.5.3 Solvents……Page 575
REFERENCES……Page 576
8.2 EMERGENCY MANAGEMENT OF DRUG ABUSE-RELATED DISORDERS……Page 580
8.2.1.3.2 Dextrose……Page 581
8.2.1.3.4 Nalmefene……Page 582
8.2.1.3.5 Flumazenil……Page 583
8.2.1.4.1 Immediate Interventions……Page 584
8.2.1.4.2 Secondary Interventions……Page 586
8.2.2.1.1 Confounding Factors……Page 587
8.2.2.1.3 Benzodiazepines vs. Neuroleptics……Page 588
8.2.2.2.1 Immediate Interventions……Page 589
8.2.2.2.2 Secondary Interventions……Page 590
8.2.3.1.1 Time Constraints (82 min)……Page 592
8.2.3.1.3 Benzodiazepines……Page 593
8.2.3.1.4 Barbiturates……Page 595
8.2.3.1.5 Phenytoin/Fosphenytoin……Page 596
8.2.3.2.1 Immediate Interventions……Page 597
8.2.3.2.2 Secondary Intereventions……Page 598
8.2.4.1.2 Mechanisms of Drug-Induced Hyperthermia……Page 599
8.2.4.1.5 Importance of Paralysis and Cooling……Page 600
8.2.4.2.1 Immediate Interventions……Page 601
8.2.5.1 General Comments……Page 604
8.2.5.1.4 Alkalinization……Page 605
8.2.5.1.7 Recommendations……Page 606
8.2.5.2.2 Secondary Intereventions……Page 607
8.2.6.1.4 Beta Blockers……Page 609
8.2.6.2.1 Immediate Interventions……Page 610
8.2.6.2.2 Secondary Intereventions……Page 611
8.2.7.1.3 Aspirin……Page 612
8.2.7.1.8 Thrombolytic Therapy……Page 613
8.2.7.1.9 Lidocaine……Page 614
8.2.7.2.1 Immediate Interventions……Page 615
8.2.7.2.2 Secondary Intereventions……Page 617
8.2.8.1.1 Mechanisms……Page 618
8.2.8.1.4 Antibiotics……Page 619
8.2.8.1.8 Acute Hypertension……Page 620
8.2.8.2.1 Immediate Interventions……Page 621
8.2.9.1 General Comments……Page 622
8.2.9.1.1 Gastric Lavage……Page 623
8.2.9.1.3 Multiple Dose Activated Charcoal……Page 624
8.2.9.2.1 Immediate Interventions……Page 625
8.2.9.2.2 Secondary Interventions……Page 626
8.2.10 MANAGEMENT OF SPECIFIC DRUGS OF ABUSE……Page 628
REFERENCES……Page 633
CHAPTER 9: SPORTS……Page 653
9.1.1 GENERAL CONSIDERATIONS……Page 655
9.1.2.1 Steroids……Page 656
9.1.3 DETECTION OF DOPING AGENTS……Page 657
9.1.5 FUTURE ALTERNATIVES……Page 658
REFERENCES……Page 659
9.2.1 STIMULANTS AND NARCOTICS……Page 660
9.2.4 CONCLUSIONS……Page 663
REFERENCES……Page 664
9.3.2 USE BY ATHLETES……Page 665
9.3.3.3 Absorption and Distribution……Page 666
9.3.4.1 Major Endocrine Regulatory Systems……Page 667
9.3.4.2.1 Mechanism of Enhanced Performance……Page 668
9.3.4.4 Hematopoietic System……Page 669
9.3.4.8 Alcoholic Hepatitis……Page 670
9.3.5.3 Plasma Lipids……Page 671
9.3.5.4.1 Myocardial Infarction and Stroke……Page 672
9.3.5.7 Psychiatric Disorders……Page 673
9.3.5.10 Other Toxic Reactions……Page 674
9.4 DETECTION OF EXOGENOUS ANABOLIC ANDROGENIC STEROIDS……Page 683
9.4.1 METABOLISM OF ANABOLIC ANDROGENIC STEROIDS……Page 684
9.4.2 ISOLATION FROM URINE……Page 687
9.4.3.1 Liquid-Liquid Extraction……Page 691
9.4.4 DERIVATIZATION OF AAS AND THEIR METABOLITES FOR GC/MS ANALYSIS……Page 692
9.4.5.1 Gas Chromatography……Page 697
9.4.5.2 Mass Spectrometry……Page 699
REFERENCES……Page 700
9.5.1 STRUCTURE OF THE GH-IGF AXIS……Page 702
9.5.3 ACROMEGALY AND GH ADMINISTRATION TO NORMAL ADULTS — RISK TO ATHLETES……Page 704
9.5.4.1 Alteration of Body Composition……Page 706
9.5.5.1 Regulators of GH Response to Exercise……Page 707
9.5.5.2 Neuroregulation of GH Response……Page 709
9.5.6.1.1 Growth Hormone Binding Protein (GH-BP)……Page 710
9.5.7 IGF AND IGF-BP LEVELS AS INDICATORS OF EXOGENOUS GH ABUSE……Page 711
9.5.9 DEVELOPMENTS IN THE DETECTION OF GH ABUSE: GH-2000……Page 712
9.5.10 IMMUNOASSAYS OF IGR AND IGFBPS……Page 713
9.5.12 OTHER POTENTIAL GH MARKERS……Page 714
9.5.13 REFERENCE RANGES……Page 715
ACKNOWLEDGMENTS……Page 716
REFERENCES……Page 717
9.6.1 EFFECTS OF HYPOXIA……Page 722
9.6.2 MANIPULATION OF BLOOD VOLUME AND RED CELL MASS……Page 723
9.6.4 ADMINISTRATION OF EXOGENOUS ERYTHROPOIETIN……Page 724
9.6.4.3 Cardiovascular Adaptation to Submaximal Exercise……Page 725
9.6.4.5 Maximal Exercise……Page 727
9.6.4.6 Muscle Physiology Data……Page 728
9.6.4.7.1 Endurance Physical Performance……Page 729
9.6.4.7.2 High-Intensity Intermittent Exercise……Page 730
REFERENCES……Page 731
9.7.1 INTRODUCTION TO THE MEDICAL CODE……Page 732
9.7.3.1 Stimulants……Page 733
9.7.3.3.1 Anabolic Androgenic Steroids……Page 734
9.7.3.4.2 Pharmaceutical, Chemical, and Physical Manipulation……Page 735
9.7.5 LABORATORIES AND TESTING PROCEDURES……Page 736
9.7.6 SAMPLING AND RESULTS……Page 737
9.7.7 CODE OF ETHICS……Page 738
CHAPTER 10: WORKPLACE TESTING……Page 739
10.1 DEVELOPMENT AND SCOPE OF REGULATED TESTING……Page 741
10.1.2 THE NIDA CONFERENCE OF 1986……Page 742
10.1.3 DRAFTING THE GUIDELINES……Page 743
10.1.4 THE “FINAL RULES”……Page 745
10.1.7 FUTURE IN REGULATED TESTING……Page 746
10.1.8 SUMMARY……Page 747
10.2.1.1 History……Page 748
10.2.1.2 Specimen Collection……Page 749
10.2.1.3 Specimen Testing……Page 750
10.2.1.4.3 Laboratory Inspection……Page 751
10.2.1.5 Review of Laboratory Results by a Medical Review Officer (MRO)……Page 753
REFERENCES……Page 754
10.2.2.2.1 Philosophy……Page 755
Standard I: Scientific Director……Page 756
Standard IV: Inspection Requirements……Page 757
10.2.2.3.3 Quality Control……Page 758
10.2.2.3.7 Computer Operations……Page 760
10.2.2.5 Toxicology Resource Committee……Page 761
REFERENCES……Page 762
10.3 ANALYTICAL CONSIDERATIONS AND APPROACHES FOR DRUGS……Page 763
10.3.1 GENERAL CONSIDERATIONS……Page 764
10.3.2 IMMUNOASSAY TESTING……Page 765
10.3.2.1 Testing for Amphetamines……Page 766
10.3.2.2 Testing for Flunitrazepam……Page 768
10.3.3.2.1 Amphetamines……Page 769
10.3.3.3 Software……Page 770
10.3.4.1 Amphetamines……Page 771
10.3.4.2 Benzodiazepines……Page 772
10.3.4.3 Morphine and Codeine……Page 773
REFERENCES……Page 774
10.4.1.1 Specimen Substitution……Page 776
10.4.1.3 In vivo adulterants……Page 777
10.4.1.4 In vitro (External) Adulterants……Page 778
10.4.2.1 Role of the Collection Site……Page 779
10.4.2.2 Role of the Laboratory……Page 780
10.4.3 INTERFERENCE NOT ASSOCIATED WITH INTENTIONAL ADULTERATION……Page 781
REFERENCES……Page 783
10.5.2 COLLECTION ISSUES……Page 785
10.5.3 DISTINCTION BETWEEN MEDICAL AND FACT-FINDING ROLES……Page 786
10.5.4 THE CONTROVERSY OVER UNAUTHORIZED PRESCRIPTIONS……Page 787
10.6 ALTERNATIVE DRUGS, SPECIMENS, AND APPROACHES FOR NON-REGULATED DRUG TESTING……Page 788
10.6.1 DRUGS OF INTEREST……Page 789
10.6.2.2 Blood……Page 790
10.6.2.3 Hair……Page 793
10.6.2.5 Saliva……Page 794
10.6.3.1 Thin Layer Chromatography (TLC)……Page 795
10.6.3.2.1 Laboratory-Based Immunoassay (LIA)……Page 796
10.6.3.4 Flame Ionization Detectors (FIDs)……Page 797
10.6.3.7 Mass Spectrometry (MS) and Tandem Mass Spectrometry (MS/MS)……Page 798
10.6.4 ON-SITE DRUG TESTING……Page 799
10.6.5 PERFORMANCE ASSESMENT BATTERIES……Page 800
10.6.6.2 What is Known? What is Needed?……Page 801
REFERENCES……Page 802
10.7.1 BACKGROUND TO RULE MAKING……Page 806
10.7.3 STANDARDS AND PROCEDURES……Page 807
10.7.4 SELECTION OF EVIDENTARY ALCOHOL TESTING……Page 808
10.7.5 WORKPLACE ALCOHOL TESTING……Page 809
REFERENCES……Page 810
CHAPTER 11: ALTERNATIVE TESTING MATRICES……Page 811
11.1 FACTORS EFFECTING DRUG DISPOSITION……Page 813
11.1.3 STABILITY OF DRUGS……Page 814
11.2.1 MECHANISMS OF DRUG INCORPORATION……Page 815
11.2.4.1 Cocaine……Page 816
11.2.4.2 Marijuana……Page 818
11.2.4.3 Common Opiates……Page 819
11.2.4.5 Amphetamines……Page 820
11.2.4.7 Benzodiazepines……Page 821
11.2.4.8 Barbiturates……Page 822
11.2.4.10 Nicotine……Page 823
11.3.1 MECHANISMS OF DRUG INCORPORATION……Page 824
11.3.1.2 Advantages and Possible Uses……Page 825
11.3.2 DETECTION OF SPECIFIC DRUGS……Page 826
11.4.1.2 Physiology……Page 828
11.4.2 ENVIRONMENTAL CONTAMINATION……Page 829
11.4.3 DOSE AND TIME RELATIONSHIPS……Page 830
11.4.5 HISTORY AND POTENTIAL APPLICATIONS……Page 831
11.5.1 MECHANISMS OF DRUG INCORPORATION……Page 833
11.5.2 FETAL DRUG UPTAKE……Page 834
11.5.3.2 Therapeutic Drugs……Page 835
11.5.3.3 Other Abused Drugs……Page 836
11.6.2 TECHNIQUES FOR MECONIUM ANALYSIS……Page 837
11.6.4 COCAINE ANALYTES……Page 838
11.6.6 POSTMORTEM ANALYSIS……Page 840
11.7 BREAST MILK……Page 841
11.7.2 OPIATES……Page 842
11.7.4 MARIJUANA……Page 843
11.7.6 STIMULANT DRUGS……Page 844
11.7.9 CONCLUSIONS……Page 845
11.8.1 MECHANISMS OF DRUG UPTAKE……Page 846
11.9.1 STRUCTURE AND FUNCTION……Page 847
11.10 SEMEN……Page 848
11.11 SEBUM……Page 849
11.14 FAT……Page 850
11.15 CONCLUSIONS……Page 851
REFERENCES……Page 856
CHAPTER 12: POSTMORTEM TOXICOLOGY……Page 870
12.1.1 MEDICOLEGAL DEATH INVESTIGATION……Page 874
12.1.1.1 The Role of Police and Medical Examiner Investigators……Page 875
12.1.1.2 Role of the Forensic Pathologist……Page 876
12.1.3.2 Suicides……Page 877
12.1.3.3 Accidents……Page 878
12.1.3.6 Pending Toxicology (Overdose)……Page 879
12.1.4.1 Poisons……Page 880
12.1.4.5 The Toxicology Report……Page 881
REFERENCES……Page 882
12.2 SPECIMEN SELECTION, COLLECTION, PRESERVATION, AND SECURITY……Page 884
12.2.2.1 Specimen Containers……Page 886
12.2.2.2 Specimen Preservatives……Page 887
12.2.3.2 Urine……Page 888
12.2.3.7 Labeling……Page 889
12.2.4.1 Blood……Page 890
12.2.4.2 Urine……Page 891
12.2.4.5 Gastric Contents……Page 892
12.2.4.6 Tissues……Page 893
12.2.4.9 Skeletal Muscle……Page 894
12.2.4.11 Meconium……Page 895
12.2.5 NON-BIOLOGICAL EVIDENCE……Page 896
REFERENCES……Page 897
12.3.2 SIMPLE CHEMICAL TESTS……Page 901
12.3.2.1.1 Trinder’s Reagent……Page 902
12.3.4.1 Cyanide Test……Page 903
12.3.6 IMMUNOASSAYS……Page 904
12.3.6.1.2 CEDIA ®……Page 905
12.3.6.4 Kinetic Interaction of Microparticles in Solution (KIMS)……Page 906
12.3.6.5.7 Propoxyphene……Page 907
12.3.7.1 Thin Layer Chromatography (TLC)……Page 908
12.3.7.2 Gas Chromatography……Page 909
12.3.7.2.1 Flame Ionization Detector (FID)……Page 910
12.3.7.3 Gas Chromatography/Mass Spectrometry (GC/MS)……Page 911
12.3.7.4 High Performance Liquid Chromatography (HPLC)……Page 912
12.3.7.4.4 Advantages and Disadvantages of HPLC……Page 913
12.3.9 SPECTROSCOPIC METHODS FOR ANALYSIS OF TOXIC METALS AND METALOIDS……Page 914
12.3.10.1.1 Liquid-Liquid Extraction……Page 915
12.3.10.1.3 pH Adjustment for Extraction……Page 916
REFERENCES……Page 917
12.4.2 GENERAL CONCEPTS……Page 937
12.4.3.3 Benzodiazepines……Page 940
12.4.3.8.1 ToxiLab ® A for Urine and Gastric Contents……Page 941
12.4.3.8.2 Alternatives to ToxiLab ®……Page 942
12.4.3.10 Screening with Gas Chromatography……Page 943
12.4.4 THE GENERAL UNKNOWN……Page 944
12.4.5.1 What Confirmation is and Why it is Necessary……Page 946
12.4.5.3 When is Confirmation Unnecessary?……Page 947
12.4.6 GAS CHROMATOGRAPHY-MASS SPECTROMETRY……Page 948
12.4.6.2 Potential Problems with GC/MS Analyses……Page 949
12.4.8.1 What Should Be Quantified?……Page 950
12.4.8.2 Specimens for Quantification of Drugs and Poisons……Page 951
12.4.8.3.3 Internal Standard……Page 952
REFERENCES……Page 953
12.5.2 STANDARD OPERATING PROCEDURES……Page 964
12.5.4 PRECISION IMPLEMENTS……Page 965
12.5.6 REFERENCE MATERIALS……Page 966
12.5.6.1 Calibrators……Page 967
12.5.6.1.1 Multi-Level Calibration……Page 968
12.5.6.2 Internal Standards……Page 969
12.5.6.3 Controls……Page 970
12.5.8.1.2 Sensitivity and Linearity……Page 973
12.5.8.1.4 Accuracy……Page 974
12.5.8.4 Method Development and Validation……Page 975
12.5.9.1 Installation……Page 976
12.5.10.2 Analytical Data……Page 977
12.5.10.3 Quality Control Data……Page 978
REFERENCES……Page 979
12.6.1 INTRODUCTION……Page 981
12.6.2.2.1 Blood……Page 982
12.6.2.2.2 Vitreous Humor……Page 983
12.6.2.2.4 Gastric Contents……Page 984
12.6.2.2.6 Brain……Page 985
12.6.2.2.9 Injection Sites, Nasal Swabs……Page 986
12.6.3 PHARMACOKINETICS……Page 987
12.6.3.2 Metabolism and Pharmacogenetics……Page 988
12.6.3.4 Estimation of Amount Ingested from Blood Levels……Page 989
12.6.4.2 Postmortem Redistribution……Page 990
12.6.5.2 Artifacts of Medication Delivery……Page 992
12.6.5.6 Interpretation Using Tables of Values……Page 993
REFERENCES……Page 994
CHAPTER 13: DRUG LAW……Page 997
13.1 CURRENT LEGAL ISSUES OF WORKPLACE DRUG TESTING……Page 998
13.1.1 THE EMPLOYMENT-AT-WILL DOCTRINE……Page 999
13.1.2.1 Discrimination — Title VII Cases……Page 1001
13.1.3 DRUG TESTING AND WORKERS’ COMPENSATION LITIGATION……Page 1002
13.1.4.1.1 Proof of Facts……Page 1004
13.1.4.1.2 The Donor’s Right to Obtain Laboratory Records Under DOT Regulations……Page 1005
13.1.4.1.3 Problems Posed by the Salmone Case……Page 1006
13.1.4.2.1 Expanding the Scope of Liability for Service Providers……Page 1007
13.1.4.2.2 Liability Exposure to the Laboratories from Drug Testing……Page 1008
13.1.5.1 Illegal Use of Drugs……Page 1009
13.1.5.4 Regulation of Alcohol and Drugs……Page 1010
13.1.5.6 Examination or Inquiry of Employees……Page 1011
13.1.5.8 Employment Entrance Examination……Page 1012
13.1.5.10.1 The Court’s Analysis of the Americans with Disabilities Act……Page 1013
13.1.6 CHARTING SAFE PASSAGE FOR THE EMPLOYER……Page 1015
13.2 DUI DEFENSES……Page 1016
13.2.1.1 Drinking After the Offense……Page 1017
13.2.1.3 Rising Blood-Alcohol Concentration……Page 1020
13.2.1.4 Pathological States and Ethanol Pharmacokinetics……Page 1022
13.2.1.5 Drug-Alcohol Interactions……Page 1024
13.2.1.7 Endogenous Ethanol and the Autobrewery Syndrome……Page 1025
13.2.2 URINE SAMPLES……Page 1026
13.2.3.1 Use of Alcohol Swabs for Skin Disinfection……Page 1029
13.2.3.2 Trauma and Intravenous Fluids……Page 1030
13.2.4 BREATH-ALCOHOL ANALYSIS……Page 1031
13.2.4.1 Mouth Alcohol and Use of Mouthwash Preparations……Page 1033
13.2.4.2 Regurgitation and Gastro Esophageal Reflux Disease (GERD)……Page 1034
13.2.4.3 Dentures and Denture Adhesives……Page 1035
13.2.4.4.1 Endogenous Breath Volatiles……Page 1036
13.2.4.4.2 Occupational Exposure to Organic Solvents……Page 1037
13.2.4.5 Variability in the Blood/Breath Alcohol Ratio……Page 1039
13.2.4.6 Pulmonary Function (Chronic Obstructive Pulmonary Disease)……Page 1041
13.2.4.7 Breathing Pattern and Hypo- and Hyperthermia……Page 1042
13.2.5 CONCLUDING REMARKS……Page 1043
REFERENCES……Page 1045
13.3.2 OVERVIEW OF FETAL RIGHTS……Page 1056
13.3.3.1 Case Law: United States Supreme Court……Page 1058
13.3.3.3 Case Law: Fetal Rights Prevail……Page 1059
13.3.4 DISCUSSION……Page 1060
13.3.5 DECISION TREE……Page 1061
REFERENCES……Page 1064
APPENDIX IA GLOSSARY OF TERMS IN FORENSIC TOXICOLOGY……Page 1066
APPENDIX IB COMMON ABBREVIATIONS……Page 1072
APPENDIX IC REFERENCES FOR METHODS OF DRUG QUANTITATIVE ANALYSIS……Page 1075
REFERENCES……Page 1084
APPENDIX II SAMPLE CALCULATIONS……Page 1119
APPENDIX III PREDICTED NORMAL HEART WEIGHT (G) AS A FUNCTION OF BODY HEIGHT IN 392 WOMEN AND 373 MEN a……Page 1122
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