Karch's Drug Abuse Handbook

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Editors
Preface
Chapter 1 Clinical Syndromes and Emergency Room Physician and Management Issues
	1.1 Medical Aspects of Drug Abuse
		1.1.1 Stimulants
			1.1.1.1 Cocaine
			1.1.1.2 Natural Stimulants
			1.1.1.3 Synthetic Stimulants
	Acknowledgments
	References
	1.2 Hallucinogens
		1.2.1 Hallucinogens
			1.2.1.1 Phenylethylamine Derivatives
			1.2.1.2 Lysergic Acid Diethylamide
			1.2.1.3 Dissociative Anesthetics
			1.2.1.4 Indolealkylamines
			1.2.1.5 Kratom
			1.2.1.6 Salvia divinorum
	References
	1.3 Cannabinoids
		1.3.1 Natural
		1.3.2 Synthetic
		1.3.3 Treatment
	References
	1.4 Opioids
		1.4.1 Opiate Effects
			1.4.1.1 Analgesic Effects
			1.4.1.2 Mental Effects
			1.4.1.3 Gastrointestinal Effects
			1.4.1.4 Respiratory Effects
			1.4.1.5 Other Effects
		1.4.2 Specific Opioid Agents
		1.4.3 Opioid Withdrawal
	Acknowledgments
	References
	1.5 Sedative-Hypnotics
		1.5.1 Benzodiazepines
		1.5.2 Phenazepam
		1.5.3 Barbiturates
		1.5.4 Gamma Hydroxybutyrate (GHB) and Analogs
		1.5.5 Solvents
		1.5.6 Management
	References
	1.6 Decreased Mental Status: Coma, Stupor, and Lethargy
		1.6.1 General Comments
		1.6.2 Approach to Management
			1.6.2.1 Immediate Interventions
			1.6.2.2 Secondary Interventions
	Acknowledgments
	References
	1.7 Agitation, Delirium, and Psychosis
		1.7.1 General Comments
			1.7.1.1 Confounders
			1.7.1.2 Initial Approach to the Agitated Patient
			1.7.1.3 Initial Pharmacological Intervention
		1.7.2 Stepwise Approach to Management
			1.7.2.1 Immediate Interventions: Safety First
			1.7.2.2 ABCs/Assess Underlying Medical Conditions
			1.7.2.3 Secondary Interventions
	References
	1.8 Seizures
		1.8.1 General Comments
		1.8.2 Stepwise Approach to Management
			1.8.2.1 Immediate Interventions
			1.8.2.2 Secondary Interventions
	Acknowledgments
	References
	1.9 Hyperthermia/Heat Stroke
		1.9.1 General Comments
		1.9.2 Stepwise Approach to Management
			1.9.2.1 Immediate Interventions
			1.9.2.2 Secondary Interventions
	Acknowledgments
	References
	1.10 Rhabdomyolysis
		1.10.1 General Comments
		1.10.2 Stepwise Approach to Management
			1.10.2.1 Immediate Interventions
			1.10.2.2 Secondary Interventions
	References
	1.11 Hypertensive Emergencies
		1.11.1 General Comments
			1.11.1.1 Hypertension
		1.11.2 Stepwise Approach to Management
			1.11.2.1 Immediate Interventions
			1.11.2.2 Secondary Interventions
	Acknowledgments
	References
	1.12 Cardiac Effects
		1.12.1 General Comments
			1.12.1.1 Sympathomimetics
			1.12.1.2 Sedative-Hypnotics
			1.12.1.3 Inhalants
			1.12.1.4 Stepwise Approach to Management
			1.12.1.5 Immediate Interventions
			1.12.1.6 Secondary Interventions
			1.12.1.7 Special Circumstances
	References
	1.13 Excited Delirium Syndrome
		1.13.1 Introduction
		1.13.2 Historical Context
		1.13.3 Pathophysiology
		1.13.4 Diagnosis
			1.13.4.1 Pre-Clinical Characteristics
			1.13.4.2 Clinical and Laboratory Characteristics
		1.13.5 Treatment
		1.13.6 Conclusion
		References
	1.14 Stroke with Drug Abuse
		1.14.1 General Comments
			1.14.1.1 Ischemic Stroke as a Complication of Drug Abuse
			1.14.1.2 Hemorrhagic Stroke as a Complication of Drug Abuse
		1.14.2 Stepwise Approach to Management
			1.14.2.1 Immediate Interventions
			1.14.2.2 Secondary Diagnostics and Interventions
	References
	1.15 Pulmonary Disease
		1.15.1 Pulmonary Manifestations of Illicit Drug Use
		1.15.2 Pulmonary Complications of Intravenous Drug Abuse
		1.15.3 Pulmonary Hypertension
		1.15.4 Aspiration Injuries
	References
	1.16 Body Packers and Stuffers
		1.16.1 General Comments
		1.16.2 Stepwise Approach to Management
	References
	1.17 Vascular Effects of Substance Abuse
		1.17.1 General Comments
			1.17.1.1 Immediate Interventions
			1.17.1.2 Secondary Interventions
			1.17.1.3 Special Circumstances
	References
	1.18 Valvular Heart Disease
		1.18.1 Introduction
		1.18.2 Epidemiology
		1.18.3 Anatomic Considerations and Pathophysiology
		1.18.4 Microbiology
		1.18.5 Macroscopic and Microscopic Findings
		1.18.6 Diagnosis
		1.18.7 Prognosis and Outcomes
		1.18.8 Fenfluramine-Associated Regurgitant Valve Disease
	Acknowledgment
	References
	1.19 Disorders of the Central Nervous System
		1.19.1 General Considerations
		1.19.2 Alcohol Related
			1.19.2.1 Alcohol Withdrawal
			1.19.2.2 Wernicke–Korsakoff Syndrome
			1.19.2.3 Vitamin B12 (Cobalamin) Deficiency
		1.19.3 Movement Disorders
			1.19.3.1 Dopamine Receptor Antagonists
			1.19.3.2 Neuroleptic Malignant Syndrome
			1.19.3.3 Serotonin Syndrome
			1.19.3.4 Nitrous Oxide (N2O
		1.19.4 CNS Infections Related to Drug Use
			1.19.4.1 Botulism
			1.19.4.2 Spinal Epidural Abscess
		1.19.5 Heroin Smoker Leukoencephalopathy
	References
Chapter 2 Pharmacokinetics: Drug Absorption, Distribution, and Elimination
	Introduction
	2.1 Basic Concepts and Models
		2.1.1 Transfer across Biological Membranes
			2.1.1.1 Passive Diffusion and Active Transport
			2.1.1.2 Absorption
		2.1.2 Biotransformation
			2.1.2.1 Phase 1 Enzymes
		2.1.3 Elimination
		2.1.4 Pharmacokinetic Parameters
			2.1.4.3 Bioavailability
			2.1.4.4 Half-Life
	References
	2.2 Toxicokinetics
	2.3 Factors Affecting Pharmacokinetic Parameters
		2.3.1 Genetic Factors
		2.3.2 Sex Differences
		2.3.3 Age
		2.3.4 Drug and Disease Interactions
	References
	2.4 Pharmacokinetics of Specific Drugs
		2.4.1 Amphetamine
			2.4.1.1 Adsorption
			2.4.1.2 Distribution
			2.4.1.3 Metabolism and Extraction
		2.4.2 Methamphetamine
			2.4.2.1 Adsorption
			2.4.2.2 Distribution
			2.4.2.3 Metabolism and Excretion
		2.4.3 3,4-Methylenedioxyamphetamine
		2.4.4 3,4-Methylenedioxymethamphetamine
			2.4.4.1 Adsorption
			2.4.4.2 Distribution
			2.4.4.3 Metabolism and Excretion
			References
		2.4.5 Barbiturates
			2.4.5.1 Pharmacology
			2.4.5.2 Adsorption
			2.4.5.3 Distribution
			2.4.5.4 Metabolism and Excretion
			References
		2.4.6 Benzodiazepines
			2.4.6.1 Pharmacology
			2.4.6.2 Adsorption
			2.4.6.3 Distribution
			2.4.6.4 Metabolism and Excretion
			References
		2.4.7 Cocaine
			2.4.7.1 Pharmacology
			2.4.7.2 Absorption
			2.4.7.3 Distribution
			2.4.7.4 Metabolism
			2.4.7.5 Elimination
			References
		2.4.8 Lysergic Acid Diethylamide
			2.4.8.1 Pharmacology
			2.4.8.2 Absorption
			2.4.8.3 Distribution
			2.4.8.4 Metabolism and Excretion
			References
		2.4.9 Cannabis and Cannabinoids
			2.4.9.1 Pharmacology
			2.4.9.2 Absorption
			2.4.9.3 Distribution
			2.4.9.4 Metabolism
			References
		2.4.10 Opiates
			2.4.10.1 Morphine
			2.4.10.2 Heroin
			2.4.10.3 Methadone
			2.4.10.4 Absorption
			2.4.10.5 Distribution
			2.4.10.6 Metabolism and excretion
			2.4.10.7 Oxycodone
			2.4.10.8 Hydrocodone
			2.4.10.9 Buprenorphine
			2.4.10.10 Tramadol
			2.4.10.11 Hydromorphone
			References
		2.4.11 Phencyclidine
			References
		2.4.12 Ketamine
			References
Chapter 3 Ethanol
	3.1 Measuring Acute Alcohol Impairment/Intoxication in the Laboratory and in Apprehended Drivers
		3.1.1 Introduction
		3.1.2 Measuring Alcohol-Induced Impairment
		3.1.3 Dose-Response Relationships
		3.1.4 Ethanol Pharmacokinetics
		3.1.5 Subjective Feelings of Intoxication
		3.1.6 Behavioral Correlates of Acute Intoxication
			3.1.6.1 Motor Control and Cognitive Functioning
			3.1.6.2 Reaction Times
			3.1.6.3 Dual-Task Performance
			3.1.6.4 Speech
			3.1.6.5 Vestibular Functions
		3.1.7 Time of Ingestion
			3.1.7.1 Rising vs Declining Limb of the BAC Curve
			3.1.7.2 Acute Tolerance
			3.1.7.3 Residual Effects of Alcohol: Hangover
		3.1.8 Impairment Testing in the Field
			3.1.8.1 Ideal Characteristics
			3.1.8.2 Reliability of Field Sobriety Tests
			3.1.8.3 Clinical Signs and Symptoms of Alcohol Influence
			3.1.8.4 Degree of Impairment in Relation to BAC
			3.1.9 Concluding Remarks
	References
	3.2 Analysis, Disposition, and Fate of Ethanol in the Body with Applications in Clinical and Forensic Toxicology
		3.2.1 Introduction
		3.2.2 Statutory Alcohol Limits for Driving
		3.2.3 Properties of Ethanol and Its Metabolites
		3.2.4 Biological Specimens for Alcohol Analysis
			3.2.4.1 Concentration Units
			3.2.4.2 Water Content of Specimens
			3.2.4.3 Hematocrit, Hemoglobin, and Blood Water
			3.2.4.4 Distribution of Ethanol between Plasma and Whole Blood
		3.2.5 Determination of Ethanol in Body Fluids
			3.2.5.1 Chemical Oxidation
			3.2.5.2 Enzymatic Oxidation
			3.2.5.3 Gas-Liquid Chromatography
			3.2.5.4 Headspace Sampling Technique
			3.2.5.5 Other Methods
		3.2.6 Breath-Alcohol Analysis
			3.2.6.1 Hand-Held Screening Instruments
			3.2.6.2 Evidential Quality Instruments
			3.2.6.3 Blood/Breath Alcohol Ratios
		3.2.7 Quality Assurance of Chemical Measurements
			3.2.7.1 Pre-Analytical Factors
			3.2.7.2 Analytical Factors
			3.2.7.3 Post-Analytical Factors
			3.2.7.4 Inter-Laboratory Proficiency Tests
			3.2.7.5 Allowing for Uncertainty
		3.2.8 Disposition and Fate of Ethanol in the Body
			3.2.8.1 Clinical Pharmacokinetics of Ethanol
			3.2.8.2 The Widmark Equation
			3.2.8.3 Michaelis-Menten Kinetics
			3.2.8.4 First-Pass Metabolism
			3.2.8.5 Inter-Individual Variations
			3.2.8.6 Intra-Individual Variations
			3.2.8.7 Effect of Eating a Meal on BAC Profiles
		3.2.9 Concluding Remarks
	References
	3.3 Determination of Ethanol in Post-Mortem Specimens: Important Considerations for Interpreting Results
		3.3.1 Introduction
		3.3.2 Importance of Blood-Ethanol Determinations
			3.3.2.1 Body Water Distribution
			3.3.2.2 Water Content of Post-Mortem (PM) Blood
			3.3.2.3 Variable Composition of Blood Specimens
			3.3.2.4 Plasma and Serum vs Whole Blood
		3.3.3 Blood-Ethanol Concentration in Unnatural Deaths
			3.3.3.1 All Causes of Death
			3.3.3.2 Acute Intoxication Deaths
			3.3.3.3 Surviving Very High Blood-Ethanol Levels
		3.3.4 Disposition and Fate of Ethanol in the Body
			3.3.4.1 Adverse Drug-Alcohol Interactions
			3.3.4.2 Induction of CYP2E1 Enzymes
		3.3.5 Post-Mortem Specimens for Ethanol Analysis
			3.3.5.1 Vitreous Humor
			3.3.5.2 Bladder Urine
			3.3.5.3 Alternative Biological Samples
		3.3.6 Stability of Ethanol in PM Blood
		3.3.7 Microbial Synthesis of Ethanol
			3.3.7.1 Extent of the Problem
			3.3.7.2 Biomarkers of PM Synthesis of Ethanol
			3.3.7.3 Differentiating the Source of Ethanol in PM Blood
		3.3.8 Alcoholic Ketoacidosis Deaths
		3.3.9 Methanol Toxicity
		3.3.10 Isopropanol Poisoning
		3.3.11 Concluding Remarks
	References
	3.4 Laboratory Tests and Biomarkers of Acute and Chronic Ethanol Consumption
		3.4.1 Introduction
		3.4.2 Diagnostic Sensitivity and Specificity
		3.4.3 Tests for Acute Alcohol Ingestion
			3.4.3.1 Determination of Ethanol in Body Fluids
			3.4.3.2 Oxidative Metabolism of Ethanol
			3.4.3.3 Determination of Methanol in Body Fluids
			3.4.3.4 Non-Oxidative Metabolites of Ethanol
			3.4.3.5 Fatty-Acid Ethyl Esters (FAEE
			3.4.3.6 Metabolites of Serotonin
		3.4.4 Laboratory Testing for Excessive Drinking
			3.4.4.1 .-Glutamyl Transferase (GGT
			3.4.4.2 Alanine and Aspartate Aminotransferase (ALT and AST
			3.4.4.3 Erythrocyte Mean Corpuscular Volume (MCV
			3.4.4.4 Carbohydrate-Deficient Transferrin (CDT
			3.4.4.5 Phosphatidylethanol (PEth
			3.4.4.6 Acetaldehyde Adducts
			3.4.4.7 Other Potential Tests or Markers of Chronic Drinking
		3.4.5 Clinical Applications of Alcohol Biomarkers
			3.4.5.1 Single Tests Versus Test Combinations
			3.4.5.2 Screening for Excessive Drinking in Unselected Populations
			3.4.5.3 Follow-up Treatment of Alcohol-Dependent Patients
		3.4.6 Genetic and Trait Markers of Alcohol Dependence
		3.4.7 Concluding Remarks
	References
	3.5 Forensic Issues Related to Ethanol Determination in Biological Specimens as Evidence for Prosecution of Traffic Offenders When Statutory Concentration Limits are Enforced
		3.5.1 Introduction
		3.5.2 Chemical Tests for Alcohol Intoxication
		3.5.3 General Challenges
			3.5.3.1 Drinking After the Offense
			3.5.3.2 Laced or Spiked Drinks
			3.5.3.3 Rising Blood-Alcohol Curve
			3.5.3.4 Retrograde Extrapolation
			3.5.3.5 Pathological States
			3.5.3.6 Drug–Alcohol Interactions
			3.5.3.7 Auto-Brewery Syndrome
			3.5.3.8 Margin of Error – Analytical Uncertainty
		3.5.4 Urine Alcohol Concentration
		3.5.5 Blood-Alcohol Analysis
			3.5.5.1 Use of Alcohol Swabs for Skin Disinfection
			3.5.5.2 Trauma, Massive Blood Loss, and Intravenous Fluids
			3.5.5.3 Hospital Versus Forensic Laboratory Results
			3.5.5.4 Low Volume of Blood in Sampling Tubes
			3.5.5.5 Type of Evacuated Tubes and Chemical Preservatives
		3.5.6 Breath-Alcohol Analysis
			3.5.6.1 Residual Mouth Alcohol
			3.5.6.2 Gastro Esophageal Reflux Disease (GERD
			3.5.6.3 Dentures and Denture Adhesives
			3.5.6.4 Interfering Substances in Breath
			3.5.6.5 Blood/Breath Alcohol Ratios
			3.5.6.6 Respiratory Function and Failure to Provide a Specimen
			3.5.6.7 Breathing Pattern
			3.5.6.8 Body and Breath-Temperature – Fever
		3.5.7 Concluding Remarks
	References
	3.6 Glossary of Terms
		3.6.1 Forensic Aspects of Ethanol
Chapter 4 Sports Drug Testing
	4.1 A Brief Introduction to Sports Drug Testing
	4.2 Anabolic Agents
		4.2.1 Endogenous Anabolic-Androgenic Steroids (AAS
			4.2.1.1 Introduction
			4.2.1.2 Individualized Steroid Profiles
		4.2.2 Isotope Ratio Mass Spectrometry (IRMS
			4.2.2.1 Carbon Isotope Ratios (CIRs
			4.2.2.2 How to Distinguish Endogenous from Exogenous Steroids
			4.2.2.3 Instrumentation and d-Values
			4.2.2.4 Current Applications of CIR in Doping Controls
			4.2.2.5 Recent Developments in IRMS in Doping Controls
		4.2.3 Exogenous AAS
			4.2.3.1 Introduction
			4.2.3.2 Instrumental Methods Applied
			4.2.3.3 Detection of Long-Term Metabolites (LTMs
		4.2.4 Conclusion
	References
	4.3 Erythropoiesis-Stimulating Agents (ESAs) – from Inorganic Agents to Biomolecules
		4.3.1 Erythropoietins and Their Detection
			4.3.1.1 Erythropoiesis
			4.3.1.2 Epoetins
			4.3.1.3 Novel Erythropoiesis-Stimulating Protein (NESP
			4.3.1.4 Continuous Erythropoietin Receptor Activator (CERA
			4.3.1.5 EPO-Fc
			4.3.1.6 Detection of EPO Abuse in Sports Drug Testing
		4.3.2 Hypoxia Inducible Factor (HIF) Stabilizers and Activators
			4.3.2.1 Regulation of Erythropoiesis through HIF
			4.3.2.2 HIF Stabilizers and Activators – Overview
		4.3.3 TGF-ß Inhibitors
			4.3.3.1 TGF-ß Cytokines and Their Role during Erythropoiesis
			4.3.3.2 ActRII-Fc Fusion Proteins: Sotatercept and Luspatercept
			4.3.3.3 TGF-ß Inhibitors in Sports Drug Testing
	References
	4.4 Peptide Hormones
		4.4.1 Introduction
		4.4.2 Growth Hormone Releasing Factors (GHRFs): Metabolism and Detection
		4.4.3 Insulins: Metabolism and Detection
		4.4.4 Other Peptides
	References
	4.5 Agents Modifying Myostatin Functions: Classification and Detection
	4.5.1 Myostatin Signaling
	4.5.2 Myostatin Inhibitors
		4.5.2.1 Therapeutic Antibodies
		4.5.2.2 ActRII-Fc Fusion Proteins: Ramatercept (ACE-031) and ACE-2494
		4.5.2.3 Follistatin-Fc (FST-Fc) Fusion Proteins: ACE-083
		4.5.2.4 Agents Derived from the Myostatin Propeptide
		4.5.2.5 Anti-Myostatin Peptibodies: PINTA-745
		4.5.2.6 Anti-Myostatin Adnectins: Talditercept Alpha/RG6206
	4.5.3 Myostatin Inhibitors in Sports Drug Testing
		4.5.3.1 Therapeutic Antibodies
		4.5.3.2 Fc Fusion Proteins
	References
	4.6 Multi-Analyte Test Methods in Sports Drug Testing: Challenges and Solutions
		4.6.1 Analysis of Highly Polar Prohibited Compounds in Sports Drug Testing
	References
	4.7 Alternative Matrices: Advantages and Limitations
		4.7.1 Dried Blood Spots (DBS
		4.7.2 Hair
		4.7.3 Oral Fluid (OF
		4.7.4 Exhaled Breath (EB
	References
Chapter 5 Genetics in Death Investigations
	5.1 Introduction
		5.1.1 Genetics, Genomics, and Personalized Medicine
		5.1.2 Phenotypic Data
		5.1.3 Determining the Cause of Death
		5.1.4 Post-Mortem Genetic Testing
		5.1.5 Specimen Retention for Post-Mortem Genetic Testing
	5.2 Pharmacogenomics in Post-Mortem Toxicology
		5.2.1 Background
			5.2.1.1 Importance of Pharmacogenetics to Variability in Drug Response
		5.2.2 Pharmacokinetics and Pharmacodynamics
			5.2.2.1 Pharmacokinetics
			5.2.2.2 Pharmacodynamics
		5.2.3 Genotype/Phenotype Relationship
		5.2.4 Post-Mortem Toxicology Case
		5.2.5 Inappropriate Uses of Pharmacogenetic Tests
	5.3 Cardiovascular Genetics and Substance Abuse
		5.3.1 Epidemiology and Genetics of Substance Abuse
			5.3.1.1 Cardiovascular Complications of Cocaine and Methamphetamine
			5.3.1.2 Cardiovascular Complications of Heroin and Intravenous Drug Abuse
		5.3.2 Post-Mortem Genetic Testing for Cardiac Channelopathies
			5.3.2.1 Long QT Syndrome
			5.3.2.2 Brugada Syndrome
			5.3.2.3 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT
			5.3.2.4 Post-Mortem Diagnosis of Inherited Arrhythmia Syndromes
		5.3.3 Post-Mortem Genetic Testing for Cardiomyopathies
			5.3.3.1 Hypertrophic Cardiomyopathy
			5.3.3.2 Dilated Cardiomyopathy
			5.3.3.3 Arrhythmogenic Cardiomyopathy
	5.4 Summary
	References
Chapter 6 Point of Collection Drug TestingSection Editor: Dennis J. Crouch
	6.1 POC Testing of Alternate Specimens (Other Than Urine
		6.1.1 Testing Devices/Techniques
			6.1.1.1 Examples of Devices
			6.1.1.2 Principle of POC Testing Methods
			6.1.1.3 Operation (General
			6.1.1.4 Evaluations of Devices
		6.1.2 Developing Technologies
		6.1.3 Conclusions
	References
	6.2 Point of Collection Testing in Criminal Justice
		6.2.1 Introduction
		6.2.2 Point of Collection Drug Testing
		6.2.3 Non-Instrumented POC Drug Tests
		6.2.4 Detection of Adulteration/Dilution
		6.2.5 Other Issues
		6.2.6 Other Technologies
		6.2.7 Regulatory Issues
		6.2.8 Legal Issues
		6.2.9 Conclusions
	References
	6.3 Regulatory Concerns for Point of Collection Testing in the Workplace
		6.3.1 Introduction
		6.3.2 POC Testing Techniques
			6.3.2.1 POC Testing Devices for Drugs of Abuse
			6.3.2.2 POC Testing Devices for Specimen Validity
		6.3.3 Regulatory Issues for POC Testing
			6.3.3.1 Evidentiary Value
			6.3.3.2 Regulatory Oversight
			6.3.3.3 POC Devices
			6.3.3.4 Trained Testers and POC Testing Sites
			6.3.3.5 Specimens
			6.3.3.6 Collection Sites and Specimen Collection
			6.3.3.7 POC Testing Procedures and Reporting Results
			6.3.3.8 Quality Control/Quality Assurance
		6.3.4 POC Testing Advantages and Disadvantages
		6.3.5 Role of the Medical Review Officer (MRO
		6.3.6 Regulatory Oversight
		6.3.7 Acknowledgments
	References
	6.4 Alcohol Determination in Point of Collection Testing
		6.4.1 Introduction
			6.4.1.1 Alcohol Abuse in the United States
		6.4.2 Pharmacology of Alcohol
			6.4.2.1 What is a “Standard Alcoholic Drink
			6.4.2.2 Alcohol in the Body
		6.4.3 APOCT Specimens and Devices
			6.4.3.1 Specimens
			6.4.3.2 Oral Fluid – Saliva
			6.4.3.3 Transdermal Alcohol Measurement – Sweat
		6.4.4 APOCT Devices
			6.4.4.1 General
			6.4.4.2 Breath Instrumentation – Evidential
			6.4.4.3 Breath Instrumentation – Evidential Screeners
			6.4.4.4 Breath Instrumentation – Non-Evidentiary Screeners
			6.4.4.5 Passive Alcohol Sensor Devices – PAS
		6.4.5 APOCT Oral Fluid/Saliva
			6.4.5.1 Analytical Principle
			6.4.5.2 Oral Fluid
			6.4.5.3 Saliva-Based Devices
	References
	6.5 Point-of-Collection (POC) Drug Testing: New Developments and Applications
		6.5.1 Introduction
		6.5.2 New Developments in Rapid Drug Testing
		6.5.3 Applications
			6.5.3.1 Urine and Oral Fluid
			6.5.3.2 Urine
			6.5.3.3 Oral fluid
		6.5.4 Continuing Evolution and Future Trends
	References
Chapter 7 Post-Mortem Toxicology
	7.1 Introduction to Post-Mortem Toxicology
		7.1.1 Medicolegal Death Investigation
			7.1.1.1 The Role of Police and Medical Examiner/Coroner’s Investigators
			7.1.1.2 Role of the Forensic Pathologist
		7.1.2 Certification of Death
		7.1.3 The Role of Toxicology in Death Investigation
			7.1.3.1 Homicides
			7.1.3.2 Suicides
			7.1.3.3 Accidents
			7.1.3.4 Natural Deaths
			7.1.3.5 Unclassified, Undetermined/Unascertained, or Pending
			7.1.3.6 Pending Toxicology (Overdose
		7.1.4 The Toxicology Examination
			7.1.4.1 Poisons
			7.1.4.2 Comprehensive Toxicology Screening
			7.1.4.3 Case Review
			7.1.4.4 Quality Assurance
			7.1.4.5 The Toxicology Report
			7.1.4.6 Toxicological Interpretation
	Acknowledgments
	References
	7.2 Post-Mortem Toxicology Sampling
		7.2.1 Chain of Custody
			7.2.1.1 Specimen Collection
			7.2.1.2 Sampling
	Acknowledgments
	References
	7.3 Common Methods in Post-Mortem Toxicology
		7.3.1 Analytical Chemistry in Post-Mortem Toxicology
			7.3.1.1 Immunoassays
			7.3.1.2 Chromatography
			7.3.1.3 Gas Chromatography
			7.3.1.4 High Performance Liquid Chromatography
			7.3.1.5 Other Applications of Mass Spectrometry
			7.3.1.6 Ultraviolet-Visible Spectrophotometry
			7.3.1.7 Sample Preparation
	Acknowledgments
	References
	7.4 Strategies for Post-Mortem Toxicology Investigation
		7.4.1 Screening Strategy
		7.4.2 General Concepts
		7.4.3 Basic Strategies
			7.4.3.1 The General Unknown
		7.4.4 Screening
			7.4.4.1 Screening by Immunoassay
			7.4.4.2 Chromatographic Methods
			7.4.4.3 Screening with Gas Chromatography
			7.4.4.4 Screening with Liquid Chromatography
		7.4.5 Confirmation
			7.4.5.1 What Confirmation Is Necessary and Why
			7.4.5.2 Gas Chromatography-Mass Spectrometry
			7.4.5.3 Potential Problems with GC/MS Analyses
			7.4.5.4 Liquid Chromatography-Mass Spectrometry
		7.4.6 Quantification of Drugs and Poisons
			7.4.6.1 What Should Be Quantified
			7.4.6.2 Specimens for Quantification of Drugs and Poisons
			7.4.6.3 The Toxicology Report
	Acknowledgments
	Notes
	References
	7.5 Quality Assurance in Post-Mortem Toxicology
		7.5.1 Introduction
		7.5.2 Accreditation
		7.5.3 Standard Operating Procedures
		7.5.4 Personnel
		7.5.5 Continuing Education
		7.5.6 Measuring Devices
		7.5.7 Reagents
		7.5.8 Reference Materials
		7.5.9 Calibrators
			7.5.9.1 Multilevel Calibration
			7.5.9.2 Method of Additions
			7.5.9.3 Internal Standards
			7.5.9.4 Controls
		7.5.10 Samples and Sampling
		7.5.11 Analytical Methods, Method Validation, and Standard Operating Procedures
			7.5.11.1 Quality of an Analytical Procedure
			7.5.11.2 Limit of Detection (LOD), Limit of Quantification (LOQ), and Limit of Reporting (LOR
			7.5.11.3 Sensitivity and Linearity
			7.5.11.4 Accuracy, Precision, and Bias
			7.5.11.5 Selectivity and Specificity
			7.5.11.6 Qualitative Methods
			7.5.11.7 Quantitative Methods
		7.5.12 Instruments
			7.5.12.1 Pre-Analysis Checklist
			7.5.12.2 Case Data
		7.5.13 Toxicology Reports and Opinions
		7.5.14 Accreditation Programs
		7.5.15 Proficiency Programs
	Acknowledgments
	Notes
	References
	7.6 Interpretation of Post-Mortem Drug Levels
		7.6.1 Introduction
			7.6.1.1 General Considerations
			7.6.1.2 Pharmacokinetics
			7.6.1.3 Post-Mortem Redistribution and Other Changes
			7.6.1.4 Other Considerations
	Acknowledgments
	References
Chapter 8 New Psychoactive Substances
	8.1 Synthetic Cannabinoids
		8.1.1 Nomenclature
		8.1.2 Chemistry
		8.1.3 Pharmacology
		8.1.4 Analytical Techniques
		8.1.5 Metabolism
		8.1.6 Pharmacokinetics and Toxicology
		8.1.7 Legal Status
	8.2 Phenethylamines
		8.2.1 Methylated Phenethylamines
			8.2.1.1 D-Series
			8.2.1.2 Benzodifurans
			8.2.1.3 Aminoindanes
		8.2.2 Methylenedioxy-phenethylamines
			8.2.2.1 N-benzyl derivatives (2C series
		8.2.3 Legal Status
	8.3 Synthetic Cathinones
		8.3.1 3,4-Methylenedioxypyrovalerone
		8.3.2 Mephedrone
		8.3.3 Methylone
		8.3.4 Butylone
		8.3.5 Pyrrolidinovalerophenone
		8.3.6 Dibutylone
		8.3.7 N-Ethyl pentylone
		8.3.8 Legal Status
	8.4 Piperazines
		8.4.1 Pharmacology and Toxicology
		8.4.2 Piperazine Derivatives
		8.4.3 Legal Status
	8.5 Pipradrol
		8.5.1 Pharmacology and Toxicology
		8.5.2 Legal Status
	8.6 Arylcyclohexylamines
		8.6.1 Ketamine
		8.6.2 Methoxetamine
		8.6.3 Methoxyphenidine
		8.6.4 Legal Status
	8.7 Tryptamines
		8.7.1 Pharmacology and Toxicology
		8.7.2 Legal Status
	8.8 Plant-Based Substances
		8.8.1 Kratom
			8.8.1.1 Pharmacology and Toxicology
			8.8.1.2 Legal Status
		8.8.2 Salvia divinorum
			8.8.2.1 Pharmacology and Toxicology
			8.8.2.2 Legal Status
	8.9 Fentanyl
		8.9.1 General Considerations
		8.9.2 Introduction
		8.9.3 Synthesis
		8.9.4 Physiochemical Properties and Pharmacokinetics
		8.9.5 Formulations
		8.9.6 Genomics
		8.9.7 Pharmacology and Pharmacokinetics
		8.9.8 Metabolism
		8.9.9 Tissue Concentrations
		8.9.10 Clinical Mechanisms
		8.9.11 Maternal Fetal Considerations
		8.9.12 Fentanyl Interactions
		8.9.13 Autopsy Findings
		8.9.14 Occupational Exposure
	8.10 Fentanyl Analogues: Metabolism and Detection
		8.10.1 Fentanyl Analogues: Individual Agents
			8.10.1.1 Acetylfentanyl
			8.10.1.2 4-anilino-N-phenethyl-4-piperidine
			8.10.1.3 Alpha-methylfentanyl
			8.10.1.4 Carfentanil
			8.10.1.5 Furanylfentanyl
		8.10.2 Synthetic Opioids
			8.10.2.1 Benzamides
	References
Chapter 9 Legal Aspects of the Opioid Epidemic
	9.1 Legal Aspects of the Opioid Epidemic
		9.1.1 Introduction
		9.1.2 Opioid Overview
			9.1.2.1 Medical Uses
			9.1.2.2 Risks of Adverse Effects
			9.1.2.3 Current Opioid Epidemic
		9.1.3 Government Efforts to Curb the Opioid Epidemic
			9.1.3.1 Legislation
			9.1.3.2 Regulatory Action
			9.1.3.3 Criminal Prosecutions and Government Investigations
		9.1.4 Litigation
			9.1.4.1 Overview of Allegations
			9.1.4.2 Manufacturers and Distributors
			9.1.4.3 Prescribers and Pharmacies
			9.1.4.4 Medical Malpractice
		9.1.5 Conclusion
	Notes
	9.2 Daubert and Testing Claims of Adverse Drug Effects in the Courtroom
		9.2.1 The Supreme Court’s Directive: Expert Testimony Must Be Derived by the Scientific Method
		9.2.2 Evaluating General Causation Evidence Under the Scientific Method
			9.2.2.1 Epidemiology
			9.2.2.2 Animal Research
			9.2.2.3 Chemical Analogies
			9.2.2.4 Case Reports/Case Series
			9.2.2.5 Secondary Source Materials
			9.2.2.6 The Scientific Method vs. Weight of the Evidence
		9.2.3 Causation Opinions Based On Clinical Reasoning
			9.2.3.1 Clinical Reasoning and General Causation
			9.2.3.2 Clinical Reasoning and Specific Causation
		9.2.4 The Parlodel® Litigation
			9.2.4.1 Plaintiffs’ Allegations Regarding Parlodel
			9.2.4.2 Opinions Admitting Plaintiffs’ Experts’ Causation Opinions
			9.2.4.3 Opinions Excluding Plaintiffs’ Experts’ Opinions
		9.2.5 Conclusion
	Notes
Appendix A: Conversion Formulas
Appendix B: Blood Ethanol Concentrations
Appendix C: Volume of Distribution Calculations
Appendix D: Normal Organ Weights
Index