Barile’s Clinical Toxicology
Crc Press Inc (Verlag)
978-1-4987-6530-5 (ISBN)
As with the two previous editions, Barile’s Clinical Toxicology: Principles and Mechanisms, Third edition, examines the complex interactions associated with clinical toxicological events as a result of therapeutic drug administration or chemical exposure. With special emphasis placed on signs and symptoms of diseases and pathology caused by toxins and clinical drugs, the new edition, examines the complex interactions associated with clinical toxicological events as a result of therapeutic drug administration or chemical exposure. The new edition presents the latest, up-to-date protocols for managing various toxic ingestions, and the antidotes and treatments associated with their pathology. In addition, the effect of toxins on a limited number of body systems and drug-induced adverse drug reactions are also covered.
KEY FEATURES
• Discusses source of the drug or chemical, pharmacological and toxicological mechanisms of action, detection, identification, and treatment
• Examines the complex interactions associated with clinical toxicological events
• Emphasizes the signs and symptoms of diseases and pathology caused by toxins and clinical drugs
• Covers effect of toxins on body systems and drug-induced adverse reactions
• Offers a unique perspective for toxicology, pharmacology, pharmacy and health professions students
The target audience for this book is undergraduate and graduate toxicology students, clinical pharmacy (Pharm.D.) students, emergency medical personnel, regulatory agencies, and other related health science professionals. It satisfies an essential need for a concise yet detailed authoritative, fundamental text addressing the current principles of clinical toxicology.
Frank A. Barile, PhD, is Professor in the Toxicology Division and past chairman of the Department of Pharmaceutical Sciences, St. John’s University College of Pharmacy and Health Sciences, New York. Dr. Barile received his BS in Pharmacy, MS in Pharmacology, and PhD in Toxicology at St. John’s University. After doing a postdoctoral fellowship in Pulmonary Pediatrics at the Albert Einstein College of Medicine, Bronx, NY, he moved to the Department of Pathology, Columbia University—St. Luke’s Roosevelt Hospital, NY, as a research associate. In these positions, he investigated the role of pulmonary toxicants in collagen metabolism in cultured lung cells. In 1984, he was appointed assistant professor in the Department of Health Sciences at City University of NY. Sixteen years later, he rejoined St. John’s University in the Department of Pharmaceutical Sciences in the College of Pharmacy. Dr. Barile holds memberships in several professional associations, including the U.S. Society of Toxicology, the American Association of University Professors, the American Association for the Advancement of Science, the American Society of Hospital Pharmacists, New York City Pharmacists Society, New York Academy of Sciences, and New York State Council of Health System Pharmacists. He is past president of the In Vitro and Alternative Methods Specialty Section of the U.S. Society of Toxicology and a former member of the Scientific Advisory Committee for Alternative Toxicological Methods, the National Institute of Environmental Health Sciences, U.S. National Institutes of Health (NIH). He is former editor of Toxicology in Vitro and Journal of Pharmacological & Toxicological Methods, published by Elsevier Ltd. Dr. Barile is the recipient of Public Health Service research grants from the National Institute of General Medical Sciences, the National Institutes of Health, and grants from private foundations dedicated to alternatives to animal testing. He has authored approximately 100 original research manuscripts, review articles, research abstracts, and conference proceedings in peer-reviewed toxicology and biomedical journals. He has also published several books and related chapters in the field. He contributed original in vitro toxicology data to the international Multicenter Evaluation for In Vitro Cytotoxicity program. He lectures regularly to pharmacy and toxicology undergraduate and graduate students in clinical and basic pharmaceutical and toxicological sciences and was awarded “Professor of the Year” for the College of Pharmacy by the St. John’s University Student Government Association (2003). Dr. Barile has served on several U.S. government advisory committees, including: Toxicology Assessment Peer Review Committee, U.S. Environmental Protection Agency; National Institutes of Health Review Panel, Study Section Reviewer (2013); Scientific Advisory Committee on Alternative Toxicological Methods (SACATM, 2005–2009); National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods, Support Contract Reviewer (2014); U.S. Food and Drug Administration (U.S. FDA), National Center for Toxicology Research, Systems Biology Subcommittee (2016); National Institute for Occupational Safety and Health (NIOSH) and Oak Ridge Associated Universities, SK Profiles Review Group (2014); U.S. Food and Drug Administration advisory committee on alternative toxicological methods (2013); and has served as vice president of the Dermal Toxicology Specialty Section for the Society of Toxicology (2013–2014). Dr. Barile received the Faculty Recognition Award, American Association of University Professors Faculty Association Award, St. John’s University, in 2003, 2004–2005, 2013–2014, and 2015–2016 and received the prestigious Public Health Service Medallion from the director of the National Institute of Environmental Health Sciences, Dr. Linda Birnbaum, for contributions to the Scientific Advisory Committee for Alternative Toxicological Methods (2009). Dr. Barile continues original research on the cytotoxic effects of therapeutic drugs, environmental chemicals, and controlled substances on cultured mammalian embryonic stem cells and human induced pluripotent stem cells and has dedicated his professional life to the advancement of in vitro alternative methods to reduce, replace and refine animal toxicology testing.
Contents
Preface...................................................................................................................xxxi
Acknowledgments............................................................................................... xxxiii
Author...................................................................................................................xxxv
Contributors........................................................................................................xxxvii
Section I □Introduction to Basic
Toxicological Principles
Chapter 1 Introduction...........................................................................................3
1.1 Introduction................................................................................3
1.2 Basic Definitions.........................................................................4
1.2.1 Toxicology.....................................................................4
1.2.2 Clinical Toxicology.......................................................4
1.3 Types of Toxicology...................................................................5
1.3.1 General Toxicology.......................................................5
1.3.2 Mechanistic Toxicology................................................5
1.3.3 Regulatory Toxicology..................................................5
1.3.4 Descriptive Toxicology..................................................6
1.4 Types of Toxicologist..................................................................7
1.4.1 Forensic Toxicologist.....................................................7
1.4.2 Clinical Toxicologist.....................................................8
1.4.3 Research Toxicologist....................................................8
1.4.4 Regulatory Toxicologist................................................8
References.............................................................................................8
Suggested Readings...............................................................................8
Review Articles.....................................................................................9
Chapter 2 Risk Assessment and Regulatory Toxicology..................................... 11
2.1 Risk Assessment....................................................................... 11
2.1.1 Introduction................................................................. 11
2.1.2 Hazard Identification/Risk Assessment (HIRA)......... 11
2.1.3 Dose–Response Evaluation......................................... 11
2.1.4 Exposure Assessment and Assessment Modeling....... 12
2.1.5 Risk Characterization.................................................. 14
2.2 Regulatory Toxicology............................................................. 16
2.2.1 Nuclear Regulatory Commission (NRC).................... 16
2.2.2 Environmental Protection Agency (EPA)................... 17
2.2.3 The Food and Drug Administration (FDA)................ 18
2.2.4 Drug Enforcement Administration (DEA).................. 19
2.2.5 Consumer Products Safety Commission (CPSC)........20
2.2.6 Occupational Safety and Health Administrations
(OSHA)........................................................................22
References...........................................................................................23
Suggested Readings.............................................................................23
Review Articles...................................................................................23
Chapter 3 Therapeutic Monitoring of Adverse Drug Reactions (ADRs).............27
3.1 Adverse Drug Reactions (ADRs) in Clinical Practice.............27
3.1.1 The Joint Commission (TJC)......................................27
3.1.2 Growing Medication Safety Concerns........................28
3.1.3 National Patient Safety Goals (NPSG).......................28
3.2 Factors that Contribute to Adverse Drug Reactions (ADRs)...29
3.2.1 Inadequate Monitoring of Prescribed Drugs..............29
3.2.2 Improper Adherence to Prescribed Directions........... 32
3.2.3 Over-Prescribing and Overuse of Medications........... 32
3.2.4 Drug–Drug and Drug–Disease Interactions............... 32
3.2.5 Allergic Reactions....................................................... 32
3.2.6 Medication Warnings.................................................. 33
3.2.7 Medication Errors....................................................... 33
3.2.8 Adverse Drug Reactions (ADRS)............................... 33
3.3 Treatment of ADRs and Poisoning in Patients......................... 35
3.3.1 History......................................................................... 35
3.3.2 Poison Control Centers (PCCs)................................... 35
3.3.3 Clinical Management of ADRs...................................36
3.3.4 Clinical Management of Toxicologic Emergencies.....36
3.4 Drug Identification and Methods of Detection......................... 41
References...........................................................................................44
Suggested Readings.............................................................................44
Review Articles................................................................................... 45
Chapter 4 Classification of Toxins in Humans.................................................... 47
4.1 Introduction.............................................................................. 47
4.2 Target Organ Classification...................................................... 47
4.2.1 Agents Affecting the Hematopoietic System.............. 47
4.2.2 Immunotoxic Agents...................................................48
4.2.3 Hepatotoxic Agents.....................................................48
4.2.4 Nephrotoxic Agents.....................................................49
4.2.5 Pulmonary Toxic Agents............................................. 52
4.2.6 Agents Affecting the Nervous System........................54
4.2.7 Agents Affecting the Cardiovascular (CV) System.... 55
4.2.8 Dermatotoxic Agents................................................... 55
4.2.9 Agents Affecting the Reproductive System................ 59
4.2.10 Agents Affecting the Endocrine System..................... 59
4.3 Classification According to use in the Public Domain.............60
4.3.1 Insecticides, Herbicides, Fungicides, and
Rodenticides (Pesticides).............................................60
4.3.2 Food and Color Additives........................................... 61
4.3.3 Therapeutic Drugs.......................................................63
4.3.4 By-Products of Combustion........................................63
4.4 Classification According to Source..........................................63
4.4.1 Botanical.....................................................................63
4.4.2 Environmental.............................................................63
4.5 Classification According to Effects..........................................64
4.5.1 Pathologic....................................................................64
4.5.2 Teratogenic, Mutagenic, and Carcinogenic.................64
4.6 Classification According to Physical State...............................64
4.6.1 Solids...........................................................................64
4.6.2 Liquids.........................................................................64
4.6.3 Gases...........................................................................65
4.7 Classification According to Biochemical Properties................65
4.7.1 Chemical Structure.....................................................65
4.7.2 Mechanism of Action or Toxicity................................65
References...........................................................................................65
Suggested Readings.............................................................................65
Review Articles...................................................................................65
Chapter 5 Exposure..............................................................................................69
5.1 Introduction..............................................................................69
5.2 Route of Exposure....................................................................69
5.2.1 Oral..............................................................................69
5.2.2 Intranasal..................................................................... 70
5.2.3 Inhalation.................................................................... 71
5.2.4 Parenteral.................................................................... 71
5.3 Duration and Frequency........................................................... 72
5.3.1 Acute Exposure........................................................... 72
5.3.2 Chronic Exposure........................................................ 73
5.3.3 Single- or Repeated-Dose Exposure........................... 73
5.4 Accumulation........................................................................... 73
5.4.1 According to Physiological Compartment.................. 74
5.4.2 According to Chemical Properties.............................. 74
5.4.3 According to Other Biological Factors........................ 74
References........................................................................................... 76
Suggested Readings............................................................................. 76
Review Articles................................................................................... 76
Chapter 6 Effects.................................................................................................. 79
6.1 General Classification............................................................... 79
6.1.1 Introduction to Principles of Immunology.................. 79
6.1.2 Chemical Allergies...................................................... 79
6.1.3 Idiosyncratic Reactions...............................................86
6.1.4 Immediate versus Delayed Effects..............................86
6.1.5 Reversible versus Irreversible Reactions.....................86
6.1.6 Local versus Systemic Effects.....................................86
6.1.7 Target Therapeutic Effects..........................................87
6.2 Chemical Interactions...............................................................87
6.2.1 Potentiation..................................................................87
6.2.2 Additive.......................................................................87
6.2.3 Synergistic...................................................................88
6.2.4 Antagonistic................................................................88
References...........................................................................................88
Suggested Readings.............................................................................88
Review Aricles.....................................................................................89
Chapter 7 Dose–Response................................................................................... 91
7.1 General Assumptions............................................................... 91
7.1.1 Types of Dose–Response Relationships...................... 91
7.1.2 Concentration–Effect and Presence at the
Receptor Site...............................................................93
7.1.3 Criteria for Measurement............................................93
7.2 LD50 (Lethal Dose 50%)...........................................................93
7.2.1 Definition.....................................................................93
7.2.2 Experimental Protocol................................................93
7.2.3 Factors That Influence the LD50..................................94
7.3 ED50 (Effective Dose 50%), TD50 (Toxic Dose 50%), and
TI (Therapeutic Index).............................................................95
7.3.1 Relationship to LD50....................................................95
7.3.2 Assumptions Using the TI...........................................95
7.4 IC50 (Inhibitory Concentration 50%)........................................96
7.4.1 Definition.....................................................................96
7.4.2 Experimental Determination.......................................97
7.4.3 For In Vitro Systems....................................................97
References...........................................................................................97
Suggested Readings.............................................................................97
Review Articles...................................................................................98
Chapter 8 Descriptive Animal Toxicity Tests......................................................99
8.1 Correlation with Human Exposure...........................................99
8.1.1 Human Risk Assessment.............................................99
8.1.2 Predictive Toxicology and Extrapolation to
Human Toxicity...........................................................99
8.2 Species Differentiation.............................................................99
8.2.1 Selection of a Suitable Animal Species......................99
8.2.2 Cost-Effectiveness..................................................... 100
8.2.3 Institutional Animal Care and Use Committee
(IACUC).................................................................... 100
8.3 Descriptive Tests..................................................................... 101
8.3.1 Required LD50 and Two Routes............................... 101
8.3.2 Chronic and Subchronic Exposure............................ 101
8.3.3 Types of Tests............................................................ 101
References......................................................................................... 102
Suggested Readings........................................................................... 102
Review Aricles................................................................................... 103
Chapter 9 In Vitro Alternatives to Animal Toxicity.......................................... 105
9.1 In Vitro Methods.................................................................... 105
9.1.1 Cell Culture Methods................................................ 105
9.1.2 Organ System Cytotoxicity....................................... 105
9.1.3 Applications to Clinical Toxicology.......................... 106
9.1.4 Relationship to Animal Experiments........................ 107
9.2 Correlation with Human Exposure......................................... 107
9.2.1 Risk Assessment........................................................ 107
9.2.2 Extrapolation to Human Toxicity.............................. 107
9.2.3 Predictive Toxicology................................................ 108
References......................................................................................... 108
Suggested Readings........................................................................... 108
Review Articles................................................................................. 108
Chapter 10 Toxicokinetics................................................................................... 111
10.1 Toxicokinetics......................................................................... 111
10.1.1 Relationship to Pharmacokinetics............................. 111
10.1.2 One-Compartment Model......................................... 111
10.1.3 Two-Compartment Model......................................... 112
10.1.4 Application to Clinical Toxicology........................... 112
10.2 Absorption.............................................................................. 112
10.2.1 Ionic and Nonionic Principles................................... 112
10.2.2 Henderson–Hasselbalch Equation and Degree of
Ionization................................................................... 114
10.2.3 Route of Administration and Solubility.................... 118
10.2.4 Absorption in Nasal and Respiratory Mucosa.......... 119
10.2.5 Transport of Molecules............................................. 120
10.3 Distribution............................................................................. 121
10.3.1 Fluid Compartments.................................................. 121
10.3.2 Ionic and Nonionic Principles................................... 122
10.3.3 Plasma Protein Binding............................................. 123
10.3.4 Lipids......................................................................... 125
10.3.5 Liver and Kidney....................................................... 125
10.3.6 Blood–Brain Barrier.................................................. 125
10.3.7 Placenta..................................................................... 125
10.3.8 Other Factors Affecting Distribution........................ 126
10.4 Biotransformation (Metabolism)............................................ 126
10.4.1 Principles of Detoxification....................................... 126
10.4.2 Phase I Reactions...................................................... 127
10.4.3 Phase II Reactions..................................................... 128
10.5 Elimination............................................................................. 131
10.5.1 Urinary...................................................................... 131
10.5.1.1 First-Order Elimination............................. 132
10.5.1.2 Zero-Order Elimination............................. 134
10.5.2 Fecal.......................................................................... 135
10.5.3 Pulmonary................................................................. 135
10.5.4 Mammary Glands..................................................... 136
10.5.5 Secretions.................................................................. 136
References......................................................................................... 136
Suggested Readings........................................................................... 136
Review Articles................................................................................. 137
Chapter 11 Chemical– and Drug–Receptor Interactions..................................... 139
Zacharoula Konsoula
11.1 Types of Chemical and Drug Receptors................................. 139
11.1.1 Ion Channels.............................................................. 139
11.1.2 G-Protein-Coupled Receptors................................... 142
11.1.3 Kinases and Enzyme-Coupled Receptors................. 143
11.1.4 Intracellular Receptors.............................................. 145
11.2 Signal Transduction................................................................ 148
References......................................................................................... 150
Suggested Readings........................................................................... 150
Review Articles................................................................................. 150
Chapter 12 Toxicogenomics................................................................................. 151
Anirudh J. Chintalapati, Zacharoula Konsoula, and Frank A. Barile
12.1 Introduction............................................................................ 151
12.2 Human Genomic Variation..................................................... 151
12.2.1 Genomic Variation in Target Molecules................... 152
12.2.2 Genomic Variation in Drug Metabolism................... 154
12.3 Gene Structure and Function.................................................. 154
12.3.1 DNA Alterations and Genotoxic Effects................... 155
12.3.2 DNA Repair Mechanisms......................................... 157
12.3.3 Experimental Monitoring for Genetic Toxicity......... 159
12.3.4 Clinical Monitoring for Genetic Toxicity.................. 159
12.4 Epigenetic Toxicology............................................................ 160
12.4.1 Mechanisms of Epigenetic Toxicity.......................... 161
12.4.1.1 DNA Methylation...................................... 161
12.4.1.2 Posttranslational Modifications of
Histone Proteins......................................... 162
12.4.1.3 Noncoding RNA........................................ 162
12.4.2 Epigenetics and Disease............................................ 163
Referenes........................................................................................... 163
Suggested Readings........................................................................... 163
Review Articles................................................................................. 164
Section II Toxicity of Therapeutic Agents
Chapter 13 Sedative/Hypnotics............................................................................ 167
Frank A. Barile and Anirudh J. Chintalapati
13.1 Barbiturates............................................................................ 167
13.1.1 History and Classification......................................... 167
13.1.2 Epidemiology............................................................ 167
13.1.3 Medicinal Chemistry................................................. 167
13.1.4 Pharmacology and Clinical Use................................ 168
13.1.5 Toxicokinetics and Metabolism................................ 168
13.1.6 Mechanism of Toxicity.............................................. 169
13.1.7 Signs and Symptoms of Acute Toxicity.................... 169
13.1.8 Emergency Guidelines.............................................. 171
13.1.9 Clinical Management of Acute Overdose................. 171
13.1.10 Tolerance and Withdrawal......................................... 172
13.1.11 Methods of Detection................................................ 172
13.2 Benzodiazepines (BZ)............................................................ 172
13.2.1 Epidemiology............................................................ 172
13.2.2 Medicinal Chemistry................................................. 173
13.2.3 Pharmacology and Mechanism of Toxicity............... 173
13.2.4 Toxicokinetics........................................................... 173
13.2.5 Signs and Symptoms of Acute Toxicity.................... 174
13.2.6 Emergency Guidelines.............................................. 174
13.2.7 Clinical Management of Acute Overdose................. 174
13.2.8 Tolerance and Withdrawal......................................... 174
13.2.9 Methods of Detection................................................ 174
13.3 Miscellaneous Sedative/Hypnotics........................................ 176
13.3.1 Chloral Hydrate......................................................... 176
13.3.2 Meprobamate (Miltown®, Equanil®)......................... 176
13.3.3 Zolpidem tartrate (Ambien®)..................................... 177
13.3.4 Buspirone (Buspar®).................................................. 177
13.3.5 Flunitrazepam (Rohypnol®)...................................... 177
13.3.6 Gamma-hydroxybutyrate (GHB)............................... 178
13.3.7 Ethchlorvynol (Placidyl®), Methaqualone
(Quaalude®), Glutethimide (Doriden®),
Methyprylon (Noludar®)............................................ 178
13.4 Methods of Detection and Laboratory Tests for S/H............. 179
References......................................................................................... 179
Suggested Readings........................................................................... 180
Review Articles................................................................................. 181
Chapter 14 Opioids and Related Agents.............................................................. 183
14.1 Opioids.................................................................................... 183
14.1.1 U.S. Public Health and Historical Use...................... 183
14.1.2 Neonatal Abstinence Syndrome (NAS).................... 185
14.1.3 Classification............................................................. 186
14.1.4 Medicinal Chemistry................................................. 189
14.1.5 Mechanism of Toxicity.............................................. 189
14.1.6 Brain Chemistry........................................................ 191
14.1.7 Toxicokinetics........................................................... 191
14.1.8 Mechanism of Toxicity.............................................. 191
14.1.9 Signs and Symptoms of Clinical Toxicity................. 192
14.1.10 Clinical Management of Acute Overdose................. 192
14.1.11 Tolerance and Withdrawal......................................... 193
14.1.12 Clinical Management of Addiction........................... 195
14.2 Specific Opioid Derivatives.................................................... 195
14.2.1 Codeine..................................................................... 195
14.2.2 Diphenoxylate............................................................ 196
14.2.3 Fentanyl..................................................................... 196
14.2.4 Meperidine................................................................ 196
14.2.5 Pentazocine............................................................... 197
14.2.6 Propoxyphene............................................................ 197
14.2.7 Hydrocodone/Oxycodone.......................................... 197
14.2.8 Tramadol................................................................... 198
14.2.9 Clonidine................................................................... 199
14.3 Methods of Detection............................................................. 199
References.........................................................................................200
Suggested Readings...........................................................................200
Review Articles................................................................................. 201
Chapter 15 Sympathomimetics............................................................................203
15.1 Amphetamines and Amphetamine-like Agents.....................203
15.1.1 Incidence...................................................................203
15.1.2 Classification.............................................................203
15.1.3 Medicinal Chemistry.................................................204
15.1.4 Pharmacology and Clinical Use................................204
15.1.5 Toxicokinetics...........................................................206
15.1.6 Effects and Mechanism of Toxicity...........................206
15.1.7 Chronic Methamphetamine Use...............................208
15.1.8 Tolerance and Withdrawal.........................................208
15.1.9 Clinical Management of Amphetamine Addiction...208
15.1.10 Methods of Detection................................................209
15.2 Cocaine...................................................................................209
15.2.1 Incidence and Occurrence.........................................209
15.2.2 Medicinal Chemistry................................................. 210
15.2.3 Pharmacology and Clinical Use................................ 210
15.2.4 Toxicokinetics........................................................... 211
15.2.5 Signs and Symptoms of Acute Toxicity.................... 212
15.2.6 Clinical Management of Acute Overdose................. 212
15.2.7 Tolerance and Withdrawal......................................... 213
15.2.8 Clinical Management of Cocaine Addiction............. 213
15.2.9 Methods of Detection................................................ 213
15.3 Xanthine Derivatives.............................................................. 213
15.3.1 Source and Medicinal Chemistry.............................. 213
15.3.2 Occurrence................................................................ 214
15.3.3 Pharmacology and Clinical Use................................ 214
15.3.4 Toxicokinetics........................................................... 216
15.3.5 Signs and Symptoms and Clinical Management
of Caffeine Toxicity................................................... 216
15.3.6 Signs and Symptoms and Clinical Management
of Theophylline Toxicity........................................... 217
15.3.7 Tolerance and Withdrawal......................................... 217
15.4 Other Specific Sympathomimetic Agents.............................. 217
15.4.1 Strychnine................................................................. 217
15.4.2 Nicotine..................................................................... 218
15.4.3 Ephedrine.................................................................. 219
15.4.4 Phenylpropranolamine..............................................220
15.4.5 Pseudoephedrine.......................................................220
References.........................................................................................220
Suggested Readings...........................................................................220
Review Articles................................................................................. 221
Chapter 16 Hallucinogenic Agents......................................................................225
16.1 History and Description.........................................................225
16.2 Ergot Alkaloids.......................................................................225
16.2.1 Incidence and Occurrence.........................................225
16.2.2 Medicinal Chemistry.................................................226
16.2.3 Pharmacology and Clinical Use................................226
16.2.4 Signs and Symptoms of Acute Toxicity....................227
16.2.5 Clinical Management of Acute Overdose.................227
16.3 Lysergic Acid Diethylamide (LSD)........................................228
16.3.1 Incidence and Occurrence.........................................228
16.3.2 Mechanism of Toxicity..............................................228
16.3.3 Hallucinogenic Effects..............................................228
16.3.4 Toxicokinetics...........................................................229
16.3.5 Signs and Symptoms of Acute Toxicity....................229
16.3.6 Clinical Management of Acute Overdose.................229
16.3.7 Tolerance and Withdrawal.........................................230
16.3.8 Methods of Detection................................................230
16.4 Tryptamine Derivatives..........................................................230
16.4.1 Incidence and Occurrence.........................................230
16.4.2 Mechanism of Toxicity..............................................230
16.4.3 Signs and Symptoms of Acute Toxicity.................... 231
16.4.4 Clinical Management of Acute Overdose................. 231
16.4.5 Tolerance and Withdrawal......................................... 231
16.4.6 Methods of Detection................................................ 231
16.5 Phenethylamine Derivatives................................................... 232
16.5.1 Incidence and Occurrence......................................... 232
16.5.2 Medicinal Chemistry................................................. 232
16.5.3 Mescaline.................................................................. 232
16.5.4 DOM (2,5-dimethoxy-4-methylamphetamine,
STP) and MDA (3,4-methylenedioxyamphetamine)...............................234
16.5.5 MDMA (3,4-methylenedioxymethamphetamine,
ecstasy)......................................................................234
16.5.6 Methods of Detection................................................ 235
16.6 Phencyclidine (1-Phenylcyclohexyl Piperidine; PCP)............ 235
16.6.1 Incidence and Occurrence......................................... 235
16.6.2 Toxicokinetics........................................................... 235
16.6.3 Signs and Symptoms of Acute Toxicity....................236
16.6.4 Clinical Management of Acute Overdose.................236
16.6.5 Tolerance and Withdrawal......................................... 237
16.6.6 Methods of Detection................................................ 237
16.7 Marijuana............................................................................... 237
16.7.1 Incidence and Occurrence......................................... 237
16.7.2 Medicinal Chemistry.................................................240
16.7.3 Receptor Pharmacology and Toxicology..................240
16.7.4 Clinical Use and Effects............................................ 241
16.7.5 Toxicokinetics...........................................................242
16.7.6 Acute Toxicity and Clinical Management.................242
16.7.7 Tolerance, Withdrawal, and Chronic Effects............242
16.7.8 Clinical Management of Chronic Addiction............. 243
16.7.9 Methods of Detection................................................ 243
16.8 Miscellaneous Hallucinogenic Agents................................... 243
16.8.1 Ketamine (Special K, Vitamin K)............................. 243
16.8.2 Gamma-hydroxybutyrate (GHB; Xyrem®)................245
16.8.3 NBOMe.....................................................................246
References.........................................................................................246
Suggested Readings...........................................................................246
Review Articles................................................................................. 247
Chapter 17 Anticholinergic and Neuroleptic Drugs............................................ 251
17.1 Introduction to Drugs Possessing Anticholinergic Effects........251
17.2 Antihistamine, Gastrointestinal, and Antiparkinson Drugs.......251
17.2.1 Incidence................................................................... 251
17.2.2 Medicinal Chemistry, Pharmacology, and
Clinical Use............................................................... 253
17.2.3 Signs and Symptoms of Acute Toxicity.................... 253
17.2.4 Clinical Management of Acute Overdose.................254
17.2.5 Methods of Detection................................................254
17.3 Tricyclic Antidepressants (TCA)............................................ 255
17.3.1 Incidence................................................................... 255
17.3.2 Medicinal Chemistry................................................. 255
17.3.3 Pharmacology and Clinical Use................................ 255
17.3.4 Toxicokinetics........................................................... 255
17.3.5 Mechanism of Toxicity..............................................256
17.3.6 Signs and Symptoms of Acute Toxicity....................256
17.3.7 Clinical Management of Acute Overdose.................256
17.3.8 Tolerance and Withdrawal......................................... 259
17.3.9 Methods of Detection................................................ 259
17.4 Phenothiazine, Phenylbutylpiperidine, and Thioxanthine
Antipsychotics........................................................................ 259
17.4.1 Classification and Indications................................... 259
17.4.2 Pharmacology and Clinical Use................................260
17.4.3 Toxicokinetics...........................................................260
17.4.4 Mechanism and Signs and Symptoms of Acute
Toxicity......................................................................260
17.4.5 Clinical Management of Acute Overdose................. 262
17.4.6 Tolerance and Withdrawal......................................... 262
17.4.7 Methods of Detection................................................ 262
17.5 Selective Serotonin Reuptake Inhibitors (SSRIS).................. 262
17.5.1 Classification and Clinical Use................................. 262
17.5.2 Pharmacology and Receptor Activity.......................263
17.5.3 Toxicokinetics...........................................................264
17.5.4 Side Effects and Adverse Reactions..........................265
17.5.5 Signs and Symptoms of Acute Toxicity....................266
17.5.6 Clinical Management of Acute Overdose (O.D.)......266
17.5.7 Tolerance and Withdrawal......................................... 267
17.5.8 Methods of Detection................................................ 267
References......................................................................................... 267
Suggested Readings........................................................................... 267
Review Articles.................................................................................268
Chapter 18 Acetaminophen, Salicylates, and Nonsteroidal Anti-
Inflammatory Drugs (NSAIDs)........................................................ 271
18.1 History and Description......................................................... 271
18.2 Acetaminophen (N-Acetyl-Para-Aminophenol,
APAP, Paracetamol)............................................................... 271
18.2.1 Incidence................................................................... 271
18.2.2 Medicinal Chemistry and Pharmacology................. 272
18.2.3 Clinical Use............................................................... 272
18.2.4 Metabolism and Mechanism of Toxicity................... 272
18.2.5 Signs and Symptoms of Acute Toxicity.................... 274
18.2.6 Clinical Management of Acute Overdose................. 274
18.3 Salicylates and Acetylsalicylic Acid (ASPIRIN, ASA).......... 276
18.3.1 Incidence and Clinical Use....................................... 276
18.3.2 Toxicokinetics...........................................................277
18.3.3 Mechanism of Toxicity..............................................277
18.3.4 Signs and Symptoms of Acute Toxicity.................... 278
18.3.5 Clinical Management of Toxicity.............................. 279
18.4 Nonsteroidal Anti-Inflammatory Agents (NSAIDS)............. 281
18.4.1 History and Description............................................ 281
18.4.2 Classification, Pharmacology, and Clinical Use.......282
18.4.3 Signs and Symptoms of Acute Toxicity....................282
18.4.4 Clinical Management of Acute Overdose.................282
18.5 Methods of Detection.............................................................284
References.........................................................................................284
Suggested Readings...........................................................................284
Review Articles.................................................................................285
Chapter 19 Anabolic–Androgenic Steroids.........................................................287
19.1 The Endocrine System...........................................................287
19.2 Neuroendocrine Physiology...................................................287
19.2.1 Description................................................................287
19.3 Anabolic–Androgenic Steroids (AAS)...................................288
19.3.1 Definition and Incidence...........................................288
19.3.2 Pharmacology and Clinical Use................................289
19.3.3 Adverse reactions......................................................289
19.3.4 Addiction and Withdrawal Syndrome.......................293
19.3.5 Treatment of the Consequences of Chronic
Steroid Use................................................................293
19.4 Estrogen and Progestins.........................................................293
19.4.1 Physiology.................................................................293
19.4.2 Pharmacology and Clinical Use................................294
19.4.3 Clinical Toxicity of Prolonged Estrogen and/or
Progestin Administration..........................................294
References.........................................................................................297
Suggested Readings...........................................................................297
Review Articles.................................................................................297
Chapter 20 Cardiovascular Toxicology................................................................299
20.1 Epidemiology..........................................................................299
20.2 Cardiovascular (CV) Physiology............................................299
20.2.1 CV Functions.............................................................299
20.2.2 Cardiac Circulation...................................................300
20.2.3 Electrophysiology......................................................300
20.2.4 The Conducting System............................................ 301
20.2.5 Electrocardiography..................................................302
20.3 Digitalis Glycosides................................................................303
20.3.1 Medicinal Chemistry.................................................303
20.3.2 Pharmacology and Clinical Use................................304
20.3.3 Toxicokinetics...........................................................304
20.3.4 Clinical Manifestations of Toxicity...........................305
20.3.5 Mechanisms of Toxicity............................................305
20.3.6 Clinical Management of Intoxication........................306
20.3.7 Methods of Detection................................................307
20.4 Beta-Adrenergic Receptor Antagonists..................................307
20.4.1 β-Adrenergic Receptor System..................................307
20.4.2 Pharmacology and Clinical Use................................307
20.4.3 Clinical Manifestations of Toxicity...........................308
20.4.4 Clinical Management of Intoxication........................308
20.5 Calcium Channel Antagonists (Ca2+ Channel Blockers)........309
20.5.1 Pharmacology and Clinical Use................................309
20.5.2 Clinical Manifestations of Toxicity........................... 310
20.5.3 Clinical Management of Intoxication........................ 310
20.6 Other CV Drugs..................................................................... 310
20.6.1 Angiotensin-Converting Enzyme (ACE)
Inhibitors................................................................... 311
20.6.2 Direct Vasodilators.................................................... 312
20.6.3 Antiarrhythmic Drugs............................................... 313
References......................................................................................... 314
Suggested Readings........................................................................... 314
Review Articles................................................................................. 315
Chapter 21 Antineoplastic Agents....................................................................... 317
21.1 Description............................................................................. 317
21.2 Review of the Cell Cycle........................................................ 317
21.3 Antimetabolites...................................................................... 318
21.3.1 Pharmacology and Clinical Use................................ 318
21.3.2 Acute Toxicity........................................................... 319
21.3.3 Clinical Management of Acute Overdose................. 319
21.4 Alkylating Agents................................................................... 320
21.4.1 Pharmacology and Clinical Use................................ 320
21.4.2 Acute Toxicity........................................................... 320
21.4.3 Clinical Management of ADRs................................. 321
21.5 Miscellaneous Chemotherapeutic Drugs............................... 321
21.5.1 Natural Products........................................................ 321
21.5.2 Hormones and Antagonists....................................... 323
21.5.3 Platinum Coordination Complexes...........................324
21.5.4 Substituted Urea........................................................324
References......................................................................................... 325
Suggested Readings........................................................................... 325
Review Articles................................................................................. 325
Chapter 22 Vitamins............................................................................................ 329
22.1 Introduction............................................................................ 329
22.2 Fat-Soluble Vitamins.............................................................. 331
22.2.1 Vitamin A and Retinoic Acid Derivatives................ 331
22.2.2 Vitamin D.................................................................. 332
22.2.3 Vitamin E.................................................................. 335
22.2.4 Vitamin K.................................................................. 335
22.3 Water-Soluble Vitamins.......................................................... 336
22.3.1 Thiamine................................................................... 336
22.3.2 Riboflavin.................................................................. 336
22.3.3 Niacin........................................................................ 336
22.3.4 Folic Acid.................................................................. 338
22.3.5 Cyanocobalamin (Vitamin B12)................................. 338
22.3.6 Ascorbic Acid (Vitamin C)....................................... 338
22.3.7 Pyridoxine (Vitamin B6)........................................... 339
22.3.8 Pantothenic Acid (Vitamin B5)................................. 339
References.........................................................................................340
Suggested Readings...........................................................................340
Review Articles.................................................................................340
Chapter 23 Herbal Remedies............................................................................... 343
23.1 Introduction............................................................................ 343
23.2 Nomenclature and Classification............................................344
23.2.1 Nomenclature............................................................344
23.2.2 Therapeutic Category................................................ 345
23.3 Indications.............................................................................. 345
23.4 Other Therapeutic and Toxicologic Information on
Herbal Products...................................................................... 345
References......................................................................................... 356
Suggested Readings........................................................................... 356
Review Articles................................................................................. 357
Section III Toxicity of Nontherapeutic Agents
Chapter 24 Alcohols and Aldehydes.................................................................... 361
24.1 Ethanol.................................................................................... 361
24.1.1 Incidence and Occurrence......................................... 361
24.1.2 Chemical Characteristics.......................................... 361
24.1.3 Toxicokinetics........................................................... 362
24.1.4 Calculation of Blood Alcohol Concentrations
(BAC)........................................................................ 363
24.1.5 Mechanisms of Toxicity............................................364
24.1.6 Clinical Manifestations of Acute Toxicity................366
24.1.7 Management of Acute Intoxication...........................368
24.1.8 Clinical Manifestations of Chronic Toxicity.............368
24.1.9 Management of Chronic Intoxication....................... 370
24.1.10 Fetal Alcohol Syndrome (FAS)................................. 371
24.1.11 Tolerance, Dependence, and Withdrawal.................. 371
24.1.12 Methods of Detection................................................ 372
24.2 Methanol................................................................................. 373
24.2.1 Incidence and Occurrence......................................... 373
24.2.2 Toxicokinetics........................................................... 373
24.2.3 Mechanism of Toxicity.............................................. 373
24.2.4 Clinical Manifestations of Acute Intoxication.......... 374
24.2.5 Management of Acute Intoxication........................... 374
24.3 Isopropanol............................................................................. 374
24.3.1 Toxicokinetics........................................................... 375
24.3.2 Mechanisms of Toxicity............................................ 375
24.3.3 Clinical Manifestations of Acute Toxicity................ 375
24.3.4 Management of Acute Intoxication........................... 375
24.4 Formaldehyde......................................................................... 375
24.4.1 Incidence and Occurrence......................................... 376
24.4.2 Toxicokinetics........................................................... 376
24.4.3 Mechanisms of Toxicity............................................ 377
24.4.4 Clinical Manifestations of Acute Intoxication.......... 377
24.4.5 Management of Acute Intoxication........................... 377
References......................................................................................... 377
Suggested Readings........................................................................... 377
Review Articles................................................................................. 378
Chapter 25 Gases................................................................................................. 381
25.1 Introduction............................................................................ 381
25.2 Pulmonary Irritants................................................................ 381
25.3 Simple Asphyxiants................................................................ 382
25.3.1 Introduction............................................................... 382
25.3.2 Gaseous Agents......................................................... 382
25.4 Toxic Products of Combustion (TCP).................................... 387
25.4.1 Introduction............................................................... 387
25.4.2 Clinical Toxicity........................................................ 387
25.5 Lacrimating Agents (Tear Gas).............................................. 389
25.5.1 Introduction............................................................... 389
25.5.2 Chemical Agents....................................................... 389
25.6 Chemical Asphyxiants............................................................ 389
25.7 Carbon Monoxide (CO).......................................................... 389
25.7.1 Incidence................................................................... 389
25.7.2 Chemical Characteristics and Sources of Exposure.....391
25.7.3 Toxicokinetics........................................................... 391
25.7.4 Mechanism of Toxicity.............................................. 391
25.7.5 Signs and Symptoms of Acute Toxicity.................... 392
25.7.6 Treatment of Acute Poisoning................................... 393
25.8 Cyanide................................................................................... 394
25.8.1 Chemical Characteristics, Occurrence, and Uses..... 394
25.8.2 Mechanism of Toxicity.............................................. 394
25.8.3 Toxicokinetics........................................................... 394
25.8.4 Signs and Symptoms of Acute Toxicity.................... 395
25.8.5 Treatment of Acute Poisoning................................... 395
25.9 Methods Of Detection............................................................397
References.........................................................................................397
Suggested Readings...........................................................................397
Review Articles................................................................................. 398
Chapter 26 Metals................................................................................................ 401
Anirudh J. Chintalapati and Frank A. Barile
26.1 Introduction............................................................................ 401
26.1.1 Background............................................................... 401
26.1.2 Exposure and Applications....................................... 401
26.1.3 Physiological Role of Metals.....................................402
26.2 Chelation Therapy..................................................................402
26.2.1 Description................................................................402
26.2.2 Dimercaprol...............................................................404
26.2.3 Ethylenediaminetetraacetic Acid (EDTA)................404
26.2.4 Penicillamine.............................................................405
26.2.5 Deferoxamine............................................................406
26.2.6 Succimer....................................................................406
26.2.7 Unithiol......................................................................407
26.3 Antimony................................................................................407
26.3.1 Physical and Chemical Properties.............................407
26.3.2 Occurrence and Uses.................................................407
26.3.3 Mechanism of Toxicity..............................................408
26.3.4 Toxicokinetics...........................................................408
26.3.5 Signs and Symptoms of Acute Poisoning.................408
26.3.6 Treatment of Acute Poisoning...................................408
26.4 Arsenic (As)............................................................................409
26.4.1 Physical and Chemical Properties.............................409
26.4.2 Occurrence and Uses.................................................409
26.4.3 Mechanisms of Toxicity............................................409
26.4.4 Toxicokinetics...........................................................409
26.4.5 Signs and Symptoms of Acute Toxicity.................... 410
26.4.6 Signs and Symptoms of Chronic Toxicity................. 410
26.4.7 Treatment of Acute Poisoning................................... 410
26.4.8 Treatment of Chronic Poisoning............................... 411
26.4.9 Carcinogenesis.......................................................... 411
26.5 Asbestos.................................................................................. 411
26.5.1 Physical and Chemical Properties............................. 411
26.5.2 Occurrence and Uses................................................. 411
26.5.3 Mechanism of Toxicity.............................................. 412
26.5.4 Toxicokinetics........................................................... 412
26.5.5 Signs and Symptoms of Acute Toxicity.................... 412
26.5.6 Signs and Symptoms of Chronic Toxicity................. 412
26.5.7 Treatment of Acute Poisoning................................... 413
26.5.8 Treatment of Chronic Poisoning............................... 413
26.6 Cadmium................................................................................ 413
26.6.1 Physical and Chemical Properties............................. 413
26.6.2 Occurrence and Uses................................................. 413
26.6.3 Mechanism of Toxicity.............................................. 414
26.6.4 Toxicokinetics........................................................... 414
26.6.5 Signs and Symptoms of Acute Toxicity.................... 414
26.6.6 Signs and Symptoms of Chronic Toxicity................. 415
26.6.7 Treatment of Acute Poisoning................................... 415
26.6.8 Treatment of Chronic Poisoning............................... 415
26.7 Cobalt..................................................................................... 415
26.7.1 Physical and Chemical Properties............................. 415
26.7.2 Occurrence and Uses................................................. 415
26.7.3 Mechanism of Toxicity.............................................. 416
26.7.4 Toxicokinetics........................................................... 416
26.7.5 Signs and Symptoms of Acute Toxicity.................... 416
26.7.6 Signs and Symptoms of Chronic Toxicity................. 416
26.7.7 Treatment of Acute Poisoning................................... 417
26.7.8 Treatment of Chronic Poisoning............................... 417
26.8 Copper.................................................................................... 417
26.8.1 Physical and Chemical Properties............................. 417
26.8.2 Occurrence and Uses................................................. 417
26.8.3 Mechanism of Toxicity.............................................. 418
26.8.4 Toxicokinetics........................................................... 418
26.8.5 Signs and Symptoms of Acute Toxicity.................... 419
26.8.6 Signs and Symptoms of Chronic Toxicity................. 419
26.8.7 Treatment of Acute Poisoning................................... 419
26.8.8 Treatment of Chronic Poisoning............................... 419
26.9 Iron (Fe2+, Fe3+)....................................................................... 420
26.9.1 Physical and Chemical Properties............................. 420
26.9.2 Occurrence and Uses................................................. 420
26.9.3 Mechanism of Toxicity.............................................. 420
26.9.4 Toxicokinetics........................................................... 421
26.9.5 Signs and Symptoms of Acute Toxicity.................... 422
26.9.6 Signs and Symptoms of Chronic Toxicity................. 422
26.9.7 Treatment of Acute Poisoning................................... 422
26.9.8 Treatment of Chronic Poisoning............................... 423
26.9.9 Clinical Monitoring................................................... 423
26.10 Lead........................................................................................ 423
26.10.1 Physical and Chemical Properties............................. 423
26.10.2 Occurrence and Uses................................................. 423
26.10.3 Mechanism of Toxicity..............................................424
26.10.4 Toxicokinetics...........................................................424
26.10.5 Signs and Symptoms of Acute Toxicity.................... 426
26.10.6 Signs and Symptoms of Chronic Toxicity................. 426
26.10.7 Treatment of Acute Poisoning................................... 426
26.10.8 Treatment of Chronic Poisoning............................... 427
26.10.9 Clinical Monitoring................................................... 427
26.11 Mercury (Hg).......................................................................... 427
26.11.1 Physical and Chemical Properties............................. 427
26.11.2 Occurrence and Uses................................................. 427
26.11.3 Occupational and Environmental Exposure............. 429
26.11.4 Mechanism of Toxicity.............................................. 429
26.11.5 Toxicokinetics........................................................... 429
26.11.6 Signs and Symptoms of Acute Toxicity
(Inhalation and Ingestion)......................................... 430
26.11.7 Signs and Symptoms of Subacute or Chronic
Poisoning................................................................... 431
26.11.8 Clinical Management of Hg Poisoning..................... 431
26.12 Selenium (Se).......................................................................... 431
26.12.1 Physical and Chemical Properties............................. 431
26.12.2 Occurrence and Uses................................................. 431
26.12.3 Physiological Role..................................................... 432
26.12.4 Mechanism of Toxicity.............................................. 432
26.12.5 Toxicokinetics........................................................... 432
26.12.6 Signs and Symptoms of Acute Toxicity.................... 433
26.12.7 Signs and Symptoms of Chronic Toxicity................. 433
26.12.8 Clinical Management of Poisoning........................... 433
26.13 Silver (Ag).............................................................................. 433
26.13.1 Physical and Chemical Properties............................. 433
26.13.2 Occurrence and Uses................................................. 433
26.13.3 Toxicokinetics........................................................... 434
26.13.4 Argyria...................................................................... 434
26.14 Zinc (Zn)................................................................................. 434
26.14.1 Physical and Chemical Properties............................. 434
26.14.2 Occurrence and Uses................................................. 434
26.14.3 Physiological Role..................................................... 435
26.14.4 Mechanism of Toxicity.............................................. 435
26.14.5 Toxicokinetics........................................................... 435
26.14.6 Signs and Symptoms of Acute Toxicity.................... 435
26.14.7 Signs and Symptoms of Chronic Toxicity................. 436
26.14.8 Clinical Management of Poisoning........................... 436
References......................................................................................... 436
Suggested Readings........................................................................... 436
Review Articles................................................................................. 437
Chapter 27 Aliphatic and Aromatic Hydrocarbons............................................. 439
27.1 Introduction............................................................................ 439
27.1.1 Aliphatic and Alicyclic Hydrocarbons...................... 439
27.1.2 Aromatic HCs............................................................ 439
27.1.3 General Signs and Symptoms of Acute Toxicity...... 439
27.2 Petroleum Distillates.............................................................. 441
27.2.1 Occurrence and Uses................................................. 441
27.2.2 Mechanism of Toxicity.............................................. 441
27.3 Aromatic Hydrocarbons......................................................... 441
27.3.1 Occurrence and Uses................................................. 441
27.3.2 Mechanism of Toxicity.............................................. 441
27.4 Halogenated Hydrocarbons....................................................443
27.4.1 Occurrence and Uses.................................................443
27.4.2 Mechanism of Toxicity..............................................444
27.5 Methods Of Detection............................................................448
References.........................................................................................448
Suggested Readings...........................................................................448
Review Articles.................................................................................449
Chapter 28 Insecticides........................................................................................ 451
28.1 Introduction............................................................................ 451
28.2 Organophosphorus Compounds (Organophosphates, OP)..... 451
28.2.1 Chemical Characteristics.......................................... 451
28.2.2 Occurrence and Uses................................................. 452
28.2.3 Mechanism of Toxicity.............................................. 453
28.2.4 Signs and Symptoms of Acute Toxicity.................... 454
28.2.5 Clinical Management of Acute Poisoning................ 455
28.3 Carbamates............................................................................. 456
28.3.1 Chemical Characteristics, Occurrence, and Uses..... 456
28.3.2 Mechanism of Toxicity.............................................. 456
28.3.3 Signs and Symptoms of Acute Toxicity.................... 456
28.3.4 Clinical Management of Acute Poisoning................ 456
28.4 Organochlorine (OC) Insecticides.......................................... 456
28.4.1 Chemical Characteristics.......................................... 456
28.4.2 Occurrence and Uses................................................. 458
28.4.3 Mechanism of Toxicity.............................................. 458
28.4.4 Signs and Symptoms of Acute Toxicity.................... 458
28.4.5 Clinical Management of Acute Poisoning................460
28.5 Miscellaneous Insecticides..................................................... 461
28.5.1 Pyrethroid Esters....................................................... 461
28.5.2 Nicotine..................................................................... 461
28.5.3 Boric Acid (H3BO3)...................................................462
28.5.4 Rotenone....................................................................462
28.5.5 Diethyltoluamide (DEET).........................................463
28.6 Methods of Detection.............................................................463
References.........................................................................................464
Suggested Readings...........................................................................464
Review Articles.................................................................................465
Chapter 29 Herbicides..........................................................................................467
29.1 Introduction............................................................................ 467
29.2 Chlorphenoxy Compounds..................................................... 467
29.2.1 Chemical Characteristics.......................................... 467
29.2.2 Occurrence and Uses.................................................469
29.2.3 Signs and Symptoms and Mechanism of Acute
Toxicity......................................................................469
29.2.4 Clinical Management of Acute Poisoning................ 470
29.3 Bipyridyl Herbicides............................................................... 470
29.3.1 Chemical Characteristics, Occurrence, and Uses..... 470
29.3.2 Toxicokinetics........................................................... 470
29.3.3 Mechanism of Toxicity.............................................. 471
29.3.4 Signs and Symptoms of Acute Toxicity.................... 472
29.3.5 Clinical Management of Acute Poisoning................ 472
29.4 Miscellaneous Herbicides....................................................... 473
29.5 Methods of Detection............................................................. 473
References......................................................................................... 475
Suggested Readings........................................................................... 475
Review Articles................................................................................. 476
Chapter 30 Rodenticides...................................................................................... 477
30.1 Introduction............................................................................ 477
30.2 Anticoagulants........................................................................ 477
30.2.1 Chemical Characteristics.......................................... 477
30.2.2 Commercial and Clinical Use................................... 479
30.2.3 Toxicokinetics...........................................................480
30.2.4 Mechanism of Toxicity..............................................480
30.2.5 Signs and Symptoms of Acute Toxicity....................480
30.2.6 Clinical Management of Acute Poisoning................ 481
30.3 Phosphorus (P)........................................................................482
30.3.1 Chemical Characteristics, Occurrence, and Uses.....482
30.3.2 Toxicokinetics...........................................................482
30.3.3 Mechanism and Signs and Symptoms of Acute
Toxicity......................................................................482
30.3.4 Clinical Management of Acute Poisoning................483
30.4 Red Squill...............................................................................483
30.4.1 Chemical Characteristics, Occurrence and Uses......483
30.4.2 Mechanism and Signs and Symptoms of Acute
Toxicity......................................................................484
30.4.3 Clinical Management of Acute Poisoning................484
30.5 Metals: Thallium, Barium......................................................484
30.5.1 Thallium (Tl).............................................................484
30.5.2 Barium (Ba)...............................................................485
30.6 Methods Of Detection............................................................485
References.........................................................................................486
Suggested readings............................................................................486
Review Articles.................................................................................487
Chapter 31 Chemical Carcinogenesis and Mutagenesis......................................489
31.1 Introduction............................................................................489
31.2 Mechanisms Of Chemical Carcinogenesis............................. 491
31.2.1 Metabolism................................................................ 491
31.2.2 Chemistry.................................................................. 491
31.2.3 Free Radicals and Reactive Oxygen Species............ 491
31.2.4 Mutagenesis...............................................................492
31.2.5 DNA Repair...............................................................494
31.2.6 Epigenetic Carcinogenesis........................................494
31.3 Multistage Carcinogenesis......................................................494
31.3.1 Tumor Initiation......................................................... 495
31.3.2 Tumor Promotion...................................................... 495
31.3.3 Tumor Progression....................................................497
31.4 Carcinogenic Characteristics..................................................497
31.4.1 Classification............................................................. 498
31.4.2 Identification.............................................................. 498
31.4.3 Carcinogenic Potential..............................................499
31.4.4 Carcinogenic Risk Assessment.................................499
31.4.5 Carcinogenic and Genotoxic Agents......................... 501
31.5 Cancer Chemoprevention....................................................... 501
31.5.1 General Considerations............................................. 501
31.5.2 Cancer Chemopreventive Agents..............................502
31.5.3 Mechanisms Underlying Cancer Chemoprevention...... 502
References.........................................................................................502
Suggested Readings...........................................................................502
Review Articles.................................................................................504
Chapter 32 Reproductive and Developmental Toxicity.......................................505
Anirudh J. Chintalapati and Frank A. Barile
32.1 Introduction............................................................................505
32.2 History and Development.......................................................506
32.3 Summary of Maternal–Fetal Physiology...............................506
32.3.1 Definitions.................................................................506
32.3.2 First Trimester...........................................................507
32.3.3 Second and Third Trimesters....................................508
32.4 Mechanisms of Developmental Toxicity................................508
32.4.1 Susceptibility.............................................................508
32.4.2 Dose–Response and Threshold.................................508
32.5 Drugs Affecting Embryonic and Fetal Development.............509
32.5.1 Classification.............................................................509
32.5.2 Drug Classes.............................................................509
32.6 Endocrine Disrupting Chemicals (Edcs)................................ 513
32.6.1 Mechanism of Toxicity.............................................. 514
32.6.2 Effects of EDCs on Female Reproductive System.... 515
32.6.3 Effects of EDCs on Male Reproductive System....... 518
32.6.4 Management of EDC Exposure................................. 519
References......................................................................................... 519
Suggested Readings........................................................................... 519
Review Articles................................................................................. 520
Chapter 33 Radiation Toxicity............................................................................. 523
33.1 Principles Of Radioactivity.................................................... 523
33.2 Ionizing Radiation.................................................................. 524
33.2.1 Biological Effects of Ionizing Radiation................... 524
33.2.2 Sources...................................................................... 524
33.2.3 Clinical Manifestations............................................. 525
33.2.4 Nuclear Terrorism and Health Effects...................... 527
33.3 Ultraviolet (UV) Radiation..................................................... 527
33.3.1 Biological Effects of Ultraviolet Radiation............... 527
33.3.2 Sources...................................................................... 528
33.3.3 Clinical Manifestations............................................. 528
33.4 Nonionizing Radiation........................................................... 531
33.4.1 Sources...................................................................... 531
33.4.2 Biological Effects and Clinical Manifestations........ 531
References......................................................................................... 532
Suggested Readings........................................................................... 532
Review Articles................................................................................. 532
Chapter 34 Chemical and Biological Threats to Public Safety........................... 535
34.1 Introduction............................................................................ 535
34.2 Biological Pathogenic Toxins as Threats to Public Safety..... 536
34.2.1 Anthrax (Bacillus anthracis)..................................... 537
34.2.2 Botulism.................................................................... 541
34.2.3 Plague (Yersinia pestis)............................................. 541
34.2.4 Brucellosis (Brucella suis)........................................ 542
34.2.5 Salmonellosis (Salmonella species).......................... 543
34.2.6 Typhoid Fever............................................................ 545
34.2.7 Shigellosis (Shigella Species)....................................546
34.2.8 Escherichia coli O157:H7.........................................546
34.2.9 Cholera (Vibrio cholerae).......................................... 547
34.2.10 Smallpox....................................................................548
34.2.11 Tularemia (Francisella tularensis), Q Fever
(Coxiella burnetti), and Viral Hemorrhagic
Fevers (VHF)............................................................549
34.3 Chemical Agents As Threats To Public Safety...................... 550
34.3.1 Nerve Gases............................................................... 550
34.3.2 Vesicants, Chemical Asphyxiants, and
Pulmonary Irritants................................................... 551
34.3.3 Ricin (Ricinus communis)......................................... 551
References......................................................................................... 552
Suggested Readings........................................................................... 552
Review Articles................................................................................. 553
Index....................................................................................................................... 555
| Erscheinungsdatum | 09.05.2019 |
|---|---|
| Zusatzinfo | 142 Tables, black and white; 92 Illustrations, black and white |
| Verlagsort | Bosa Roca |
| Sprache | englisch |
| Maße | 156 x 234 mm |
| Gewicht | 1038 g |
| Themenwelt | Geisteswissenschaften ► Psychologie ► Allgemeine Psychologie |
| Geisteswissenschaften ► Psychologie ► Biopsychologie / Neurowissenschaften | |
| Medizin / Pharmazie ► Allgemeines / Lexika | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie | |
| Naturwissenschaften ► Biologie | |
| ISBN-10 | 1-4987-6530-0 / 1498765300 |
| ISBN-13 | 978-1-4987-6530-5 / 9781498765305 |
| Zustand | Neuware |
| Haben Sie eine Frage zum Produkt? |
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