Since 1975, Robert Julien's A Primer of Drug Action has been the definitive guide to the effects of psychoactive drugs on the brain and on behavior. Now fully updated, this popular guide continues to lead the way through a rapidly changing field, providing readers with a clear, contemporary, and objective look at every drug and medication that either positively or adversely affects brain function. This edition includes important new information on -Herbal medications -Drug therapy for behavioral and anxiety disorders -Clinical practice guidelines for treating psychological disorders -Depression and the action of antidepressant drugs -The use of newer anticonvulsants in the treatment of bipolar disorder, pain syndromes, and behavioral disorders -Drug therapy for children, adolescents and the elderly -"New generation" antipsychotic agents Authoritative, comprehensive, and suitable for those with little background in biology, A Primer of Drug Action is an indispensable source of information for anyone interested in drug use, abuse, and education.

Robert M. Julien, M.D., Ph.D., is staff anesthesiologist at St. Vincent Hospital and Medical Center in Portland, Oregon.

Preface

xi

Part 1 Introduction to Psychopharmacology How Drugs Interact with the Body and the Brain

1

(50)

Pharmacokinetics: How Drugs Are Handled the Body

2

(21)

Drug Absorption

Drug Distribution

Termination of Drug Action

Time Course of Drug Distribution and Elimination: Concept of Drug Half-Life

Drug Half-Life, Accumulation, and Steady State

Therapeutic Drug Monitoring

Drug Tolerance and Dependence

Pharmacodynamics: How Drugs Act

23

(12)

Receptors for Drug Action

Dose-Response Relationship

Drug Safety and Effectiveness

The Neuron, Synaptic Transmission, and Neurotransmitters

35

(16)

Overall Organization of the CNS

The Neuron

Specific Neurotransmitters

Part 2 Drugs That Depress Brain Function: Sedative-Hypnotic Drugs

51

(64)

Ethyl Alcohol and the Inhalants of Abuse

52

(30)

Ethyl Alcohol

Pharmacology of Alcohol

Alcoholism and Its Pharmacological Treatment

Inhalants of Abuse

Why Inhalants Are Abused and Who Abuses Them

Acute Intoxication and Chronic Effects

Barbiturates, General Anesthetics, and Antiepileptic Drugs

82

(18)

Historical Background

Sites and Mechanisms of Action

Uses

Sedative-Induced Brain Dysfunction

Specific CNS Depressants

Barbiturates

Miscellaneous Nonbarbiturate Sedative-Hypnotic Drugs

General Anesthetics

Antiepileptic Drugs

Relationships Between Structure and Activity

Antiepileptic Drugs in Pregnancy

Benzodiazepines and Second-Generation Anxiolytics

100

(15)

Benzodiazepines

Mechanism of Action: The Benzodiazepine-GABA Receptor

Pharmacokinetics

Pharmacological Effects

Uses

Side Effects and Toxicity

Tolerance and Dependence

Effects in Pregnancy

Flumazenil: A GABAA Antagonist

Second-Generation Anxiolytics

Zolpidem

Zaleplon and Zopiclone

Partial Agonists at GABAA Receptors

Serotoninergic Drugs as Anxiolytics

Part 3 Drugs That Stimulate Brain Function: Psychostimulants

115

(50)

Cocaine, Amphetamines, and Other Behavioral Stimulants

116

(29)

Cocaine

Background

Forms of Cocaine

Pharmacokinetics

Mechanism of Action

Effects of Short-Term, Low-Dose Use

Toxic and Psychotic Effects of Long-Term, High-Dose Use

Comorbidity

Cocaine and Pregnancy

Pharmacological Treatment of Cocaine Dependency

Psychosocial Interventions

Amphetamines and Other Behavioral Stimulants

History

Mechanism of Action

Pharmacological Effects

Dependence and Tolerance

ICE: A Free-Base Form of Methamphetamine

Nonamphetamine Behavioral Stimulants

Pharmacologic Treatment of ADHD

Caffeine and Nicotine

145

(20)

Caffeine

Pharmacokinetics

Pharmacological Effects

Mechanism of Action

Reproductive Effects

Tolerance and Dependence

Nicotine

Pharmacokinetics

Pharmacological Effects

Mechanism of Action

Tolerance and Dependence

Toxicity

Therapy for Nicotine Dependence

Part 4 Drugs That Relieve Pain: Opioid and Nonopioid Analgesics

165

(36)

Opioid Analgesics

166

(25)

History

Terminology

Opioid Receptors

Classification of Opioid Analgesics

Morphine: A Pure Agonist Opioid

Other Pure Agonist Opioids

Partial Agonist Opioids

Mixed Agonist-Antagonist Opioids

Antagonist Opioids

Pharmacotherapy of Opioid Dependence

Nonnarcotic, Anti-inflammatory Analgesics

191

(10)

Nonselective Cyclooxygenase Inhibitors

Selective COX-2 Inhibitors

Part 5 Drugs That Possess Hallocinogenic or Psychedelic Properties

201

(46)

Tetrahydrocannabinol

202

(19)

History

Mechanism of Action: The Cannabinoid Receptor

Pharmacokinetics

Pharmacological Effects of THC and Anandaminde in Animals

Pharmacological Effects in Humans

Side Effects

Tolerance and Dependence

Therapeutic Uses

Psychedelic Drugs: Mescaline, LSD, and Other Hallucinogens

221

(26)

Anticholinergic Psychedelics: Scopolamine

Catecholamine-like (Phenethylamine) Psychedelics

Serotonin-like Psychedelics

Phencyclidine and Ketamine: Psychedelic Anesthetics, Amnestics, and Deliriants

Part 6 Drug Abuse

247

(34)

Topics in Substance Use Disorders

248

(19)

Historical Perspective

Nosology and Epidemiology of Substance Dependence and Abuse

Psychoactive Drugs as Behavioral Reinforcers

Drug Availability

Drug Education

Treatment Issues

Pharmacotherapy of Substance Use Disorders

Anabolic-Androgenic Steroids

267

(14)

Mechanism of Action and Effects

Physical Dependence

Abuse and Treatment

Androstenedione

Part 7 Drugs That Are Used to Treat Psychological Disorders

281

(130)

Drugs Used to Treat Depression

283

(28)

Evolution of Antidepressant Drug Therapy

Mechanism of Antidepressant Drug Action

Tricyclic Antidepressants

Second-Generation (Atypical) Antidepressants

Serotonin-Specific Reuptake Inhibitors (SSRIs)

Dual-Action Antidepressants

Monoamine Oxidase Inhibitors (MAOIs)

COMT Inhibitors

Specific Norepinephrine Reuptake Inhibitor (SNRI)

Serotonin 5-HT1 Agonists

Dehydroepiandrosterone (DHEA)

S-adenosy-methionine (SAM; SAMe)

Drugs Used to Treat Bipolar Disorder

311

(18)

Lithium

Anticonvulsants

Atypical Antipsychotics

Acetylcholine Esterase Inhibitors

Omega-3 Fatty Acids

Miscellaneous Agents

Psychotherapeutic and Psychosocial Treatments

Drugs Used to Treat Schizophrenia: Antipsychotic Drugs

329

(29)

Etiology of Schizophrenia

Overview of Antipsychotic Drugs

Phenothiazines

Haloperidol

Atypical Antipsychotics

Antipsychotic Drugs in the Young and the Elderly

Drugs Used to Treat Parkinsonism

358

(8)

Levdopa (L-dopa)

Dopamine Receptor Agonists

Selegiline

Muscarinic Receptor Antagonists

Nonpharmacologic Treatments

Integration of Drugs and Psychological Therapies in Treating Mental and Behavior Disorders

366

(29)

Robert M. Julien

Donald E. Lange

Undertreatment of Mental and Psychological Disorders

Depression

Role of Drugs as Cotherapy

Role of Psychotherapy as Cotherapy

Role of the Treatment Team

DSM-IV Classification of Mental Disorders

Mood Disorders

Schizophrenia

Anxiety Disorders

Eating Disorders

Practice Standards

Herbal Medicines Used in the Treatment of Psychological Disorders

395

(16)

St. John's Wort

Gingko

Kava

Ephedrine (Ma-huang)

Other Herbals with CNS Activity

Conclusions

Glossary

411

(8)

References

419

(69)

Index

488

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