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1 ^ PRIMER OF DRUG ACTION A comprehensive gyide to the actions, uses, and side effects of psychoactive drugs wm, ROBERT M.JULIEN M.D.. PH.D. Claire D. Advokat, Ph.D. Louisiana State University and Joseph E. Camaty. Ph.D.. M.P. Louisiana State Office of Mental Health WORTH PUBLISHERS

2 Contents Preface xi Part 1 Introduction to Psychopharmacology: How Drugs Interact with the Body and the Brain 1 1 Pharmacokinetics: How Drugs Are Handled by the Body 3 Drug Absorption / Drug Distribution / Termination of Drug Action / Time Course of Drug Distribution and Elimination: Concept of Drug Half-Life 2 Pharmacodynamics: How Drugs Act 38 Receptors for Drug Action / Dose-Response Relationships / Drug Safety and Effectiveness 3 The Neuron, Synaptic Transmission, and Neurotransmitters 63 Overall Organization of the Brain / The Neuron / Specific Neurotransmitters

3 Part 2 Drugs That Depress Brain Function: Sedative- Hypnotic Drugs 93 4 Ethyl Alcohol and the Inhalants of Abuse 95 Ethyl Alcohol Pharmacology of Alcohol / Tolerance and Dependence / Side Effects and Toxicity / Teratogenic Effects / Alcoholism and Its Pharmacological Treatment Inhalants of Abuse Why Inhalants Are Abused and Who Abuses Them / Medical Consequences of Inhalant Abuse / Acute Intoxication and Chronic Effects Chapter 4 Appendix: What Is a Drink? How Much Alcohol Is in My Drink? 5 Barbiturates, General Anesthetics, Gamma Hydroxybutyrate (GHB), and Antiepileptic Drugs 146 Historical Background / Sites and Mechanisms of Action / Sedative-Induced Brain Dysfunction Specific Depressants Barbiturates / Nonbarbiturate Sedative-Hypnotic Drugs General Anesthetics Gamma Hydroxybutyrate Antiepileptic Drugs Relationships Between Structure and Activity / Specific Agents / Antiepileptic Drugs in Pregnancy 6 Benzodiazapines and Related Anxiolytic Medications 169 Benzodiazepines / Flumazenil: A Benzodiazepine Receptor Agonist / Benzodiazepine Receptor Agonist Hypnotics / Ramelteon: A Selective Melatonin Receptor Agonist / Serotonin Receptor Agonists as Anxiolytics / Anticonvulsants as Anxiolytics

4 Part 3 Drugs That Are Used to Treat Psychological Disorders Antidepressant Drugs 197 Depression / First-Generation Antidepressants / Second- Generation Antidepressants / Selective Serotonin Reuptake Inhibitors / Dual-Action Antidepressants / Dopamine- Norepinephrine Reuptake Inhibitor: Bupropion / Selective Norepinephrine Reuptake Inhibitors / STAR*D Study / Antidepressants of the Future 8 Drugs Used to Treat Bipolar Disorder 252 Bipolar Disorder / STEP-BD Study / Lithium / "Neuromodulator" Anticonvulsant Mood Stabilizers / Other Uses for Anticonvulsant Mood Stabilizers / Atypical Antipsychotics / Omega-3 Fatty Acids / Miscellaneous Agents / Psychotherapeutic and Psychosocial Treatments 9 Antipsychotic Drugs 294 Schizophrenia / Historical Background and Classification of Antipsychotic Drugs / CATIE and CUtLASS Studies / First- Generation Antipsychotic Drugs: Phenothiazines / Alternative First-Generation Antipsychotics / Second-Generation (Atypical) Antipsychotic Drugs / Prominent Side Effects of Second- Generation Antipsychotics / Additional Applications for Second-Generation Antipsychotics 10 Child and Adolescent Psychopharmacology 341 Behavioral and Aggressive Disorders / Autism Spectrum Disorders / Attention Deficit/Hyperactivity Disorder / Depression in Children and Adolescents / Anxiety Disorders in Children and Adolescents / Bipolar Disorder in Children and Adolescents / Psychotic Disorders in Children and Adolescents 11 Geriatric Psychopharmacology 391 Inappropriate Drug Use in the Elderly / Control of Agitated and Aggressive Behaviors in the Elderly / Undertreatment of the Elderly: Focus on Depression / Parkinsons Disease / Alzheimer's Disease

5 12 Integrating Psychopharmacology and Psychological Therapies in Patient Care 420 Limitations to Pharmacological Therapy / Developing a Plan to Integrate Psychopharmacology and Psychological Therapies / Clinical Examples / Limitations to Current Practice / Examples of Areas of Needed Involvement Chapter 12 Appendix: Quick Reference to Psychotropic Medication Part 4 Drugs That Stimulate Brain Function: Psychostimulants Cocaine, the Amphetamines, and Nonamphetamine Behavioral Stimulants 441 Cocaine Forms of Cocaine / Pharmacokinetics / Mechanism of Action / Pharmacological Effects in Human Beings / Comorbidity / Cocaine and Pregnancy / Neurotoxicity of Cocaine / Pharmacological Treatment of Cocaine Dependency / Novel Approaches to the treatment of Cocaine Addiction Amphetamines Mechanism of Action / Pharmacological Effects / Dependence and Tolerance / Methamphetamine Nonamphetamine Behavioral Stimulants 14 Caffeine and Nicotine 479 Caffeine Pharmacokinetics / Pharmacological Effects / Mechanism of Action / Reproductive Effects / Tolerance and Dependence Nicotine Pharmacokinetics / Pharmacological Effects / Mechanism of Action / Tolerance and Dependence / Toxicity / Effects of Passive Smoke / Effects During Pregnancy / Therapy for Nicotine Dependence

6 Part 5 Analgesic Drugs and Psychedelics Nonnarcotic Anti-Inflammatory Analgesics 515 Nonselective Cyclooxygenase Inhibitors / Selective COX-2 Inhibitors / Nonopioid Analgesics of the Future: Nitric Oxide- Donating Analgesics 16 Opioid Analgesics 529 History / Terminology / Opioid Receptors / Classification of Opioid Analgesics / Morphine: A Pure Opioid Agonist / Other Pure Opioid Agonists / Partial Opioid Agonists / Mixed Agonist-Antagonist Opioids / Pure Opioid Antagonists / Opioid Combinations / Pharmacotherapy of Opioid Dependence 17 Cannabinoid Agonists and Antagonists 572 History / Mechanism of Action: Cannabinoid Receptor / Pharmacokinetics / Pharmacological Effects / Tolerance and Dependence / Therapeutic Uses of Cannabinoid Agonists / Cannabinoid Antagonists 18 Psychedelic Drugs 606 Scopolamine: An Anticholinergic Psychedelic/ Catecholaminelike Psychedelics / Serotoninlike Psychedelics / Glutaminergic NMDA Receptor Antagonists / Salvinorin A Part 6 Special Topics in Psychopharmacology Herbal Medicines for Psychological Disorders 639 St. John's Wort / Ginkgo / Kava / Ephedrine (Ma-Huang) / Other Herbals That Act on the CNS / Conclusions 20 Anabolic Steroids 661 Mechanism of Action / Effects / Side Effects / Physical Dependence / Abuse and Treatment

7 CONTENTS 21 Topics in Drug Abuse 683 Historical and Current Perspectives / Extent of the Drug Problem / Nosology and Psychopathology of Substance Abuse / Drugs as Behavioral Reinforcers: Neurobiology of Drug Dependence / Drug Availability / Addiction as a Chronic, Relapsing Illness / Drug Education / Treatment Issues / Pharmacotherapy of Substance Use Disorders Glossary 709 Index 717

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