Julien's Primer of Drug Action

About this Book
	Cover Page
	Accessibility
	Halftitle Page
	Title Page
	Copyright Page
	About the Authors
	Brief Contents
	Contents
	Preface
	Halftitle Page
Part 1 Introduction to Psychopharmacology
	Chapter 1 Pharmacokinetics: How the Body Handles Drugs
		Drug Absorption
			Oral Administration
			Rectal Administration
			Administration by Inhalation
			Administration Through Mucous Membranes
			Administration Through the Skin
			Administration by Injection
		Drug Distribution
			Distribution in the Bloodstream
			Body Membranes That Affect Drug Distribution
		Termination of Drug Action
			Biotransformation (Drug Metabolism)
			Role of the Kidneys and Liver in Drug Elimination
		Time Course of Drug Distribution and Elimination: The Concept of Drug Half-Life
		Drug Accumulation and Steady-State Concentration
		Therapeutic Drug Monitoring
		Drug Tolerance and Drug Dependence
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 2 Brain, Neurons, Synaptic Transmission, and Neurotransmitters
		Central Nervous System and Peripheral Nervous System
		Brain and Spinal Cord
			Divisions, Structures, and Functions of the Brain
			Human Connectome Project and BRAIN Project
		Neurons and Synapses
		Synaptic Transmission and Neurotransmitters
			Neurotransmitter Families
			Acetylcholine
			Catecholamines: Norepinephrine and Dopamine
			Serotonin
			Amino Acid Neurotransmitters
			Peptide Neurotransmitters
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 3 Pharmacodynamics: How Drugs Act
		Receptors and Drug Action
			Receptor Structure
			Acute and Chronic Receptor Effects
		Dose-Response Relationships
			Potency and Efficacy
			Agonists and Antagonists
		Responsiveness to Drugs
			Variability
			The Therapeutic Index
			Drug Interactions: Polypharmacy
			Dosing and Clinical Oversight
			Drug Toxicity
			Placebos
		End of Chapter
			Chapter Review
			Key Terms
Part 2 Pharmacology of Drugs of Abuse
	Chapter 4 Addiction: Terminology, Epidemiology, Neurobiology, and Pharmacology
		Terminology and the Concept of Addiction
		The Addiction Problem: Extent, Comorbidities, and Attempts at Solutions
			Comorbidities
			Attempts at Solutions
		The Brain-Disease Model of Addiction
			A Closer Look at Addiction and the Reward Circuit of the Brain
			Brain-Derived Neurotrophic Factor and Craving for Drugs
			Criticism of the Brain-Disease Model of Addiction
		Pharmacotherapy of Addictions
			Full-Agonist Substitution Treatment
			Partial-Agonist Substitution Treatment
			Treatment with Antagonists
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 5 Ethyl Alcohol and the Inhalants of Abuse
		Ethyl Alcohol
			Alcoholism and Alcoholic Beverages: An Overview
			Pharmacokinetics of Ethanol
			Effects of Ethanol on Brain, Body, Psychology, and Behavior
			Ethanol Tolerance, Dependence, and Withdrawal
			Pharmacotherapies for Alcohol Use Disorder or Alcoholism
		Inhalants of Abuse
			Acute Consequences of Inhalant Abuse
			Long-Term Consequences of Chronic Inhalant Abuse
			Treatment of Inhalant Abuse
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 6 Caffeine and Nicotine
		Caffeine
			Pharmacokinetics
			Mechanism of Action
			Effects of Caffeine
			Tolerance and Dependence
		Nicotine
			Epidemiology and Public Policy
			Pharmacokinetics
			Mechanism of Action
			Effects of Nicotine
			Adverse Effects of Tobacco Smoking
			Tolerance and Dependence
			Pharmacological Treatment of Nicotine Dependence
			Cessation of Smoking: Health Benefits and Factors to Consider
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 7 Psychostimulants: Cocaine, Amphetamines, and Nonamphetamines
		Cocaine
			History of Use
			Forms of Cocaine
			Pharmacokinetics
			Mechanism of Action
			Pharmacological Effects
			Comorbidity
			Treatment of Cocaine Dependence
		Amphetamines
			History
			Mechanism of Action
			Pharmacological Effects
			Methamphetamine
			Treatment of Amphetamine Use Disorder, Including Methamphetamine Use Disorder
		Nonamphetamines
			Ephedrine and Pseudoephedrine
			Khat
			Synthetic Cathinones
			DMAA
			Prescription-Only Nonamphetamines
		Psychostimulant Use During Pregnancy
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 8 Psychedelic Drugs
		Catecholaminelike and Amphetaminelike Psychedelics
			Naturally Occurring Compounds
			Synthetic Compounds
		Serotoninlike Psychedelics
			LSD (Lysergic Acid Diethylamide)
			Other Serotoninlike Compounds
		Acetylcholine Muscarinic Receptor Antagonist: Scopolamine
			Historical Background
			Pharmacological Effects
		Glutamate NMDA Receptor Antagonists: Phencyclidine, Ketamine, and Esketamine
			Pharmacokinetics
			Mechanism of Action
			Psychological and Physical Effects
		Opioid Kappa Receptor Agonist: Salvinorin A
			Mechanism of Action
			Psychological and Physical Effects
		Psychedelic Medicine: Therapeutic Applications of Psychedelic Drugs
			Psilocybin
			LSD
			Ayahuasca
			Mescaline and MDMA
			Salvinorin A
			Ketamine and Esketamine
			Methoxetamine
			Dextromethorphan
			Kratom
			Tianeptine
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 9 Cannabis
		What is Cannabis?
		History and Current Issues
			Cultivation and Manufacture
			Legal Issues
			Epidemiology
			Synthetic Cannabinoids
		Cannabinoid Receptors and the Actions of THC, CBD and the Neurotransmitter Anandamide
		Pharmacokinetics of THC
			Absorption
			Distribution
			Metabolism and Elimination
		Pharmacokinetics of CBD
		Pharmacological Effects of THC
			Physiological Effects
			Psychological and Psychomotor Effects
		Therapeutic Applications of Cannabinoids
			Cannabinoids for Nonpsychiatric Disorders
			Cannabinoids for Psychiatric Disorders
		Cannabis Tolerance, Withdrawal, Dependence, and Addiction
			Tolerance
			Withdrawal
			Dependence and Addiction: Cannabis Use Disorder
			Treatment of Cannabis Use Disorder
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 10 Opioids
		History of Opioid Use
		The Opioid Epidemic
		Pain and Pain Transmission
			Acute Pain and Chronic Pain
			Pain Transmission
		Opioid Receptors
		Pharmacological Effects of Opioids
			Analgesia
			Euphoria
			Sedation and Anxiolysis
			Respiratory Depression
			Gastrointestinal Effects
			Endocrine Effects
			Effects in Pregnancy
			Other Effects
			Effects of Genetic Influences on Opioid Metabolism
		Specific Opioids
			Full Opioid Agonists
			Morphine
			Partial Opioid Agonists
			Mixed Agonist–Antagonist Opioids
			Opioid Antagonists
			Novel Opioid-Based Compounds Under Development
		Illicit Opioids of Abuse
			Heroin
			Synthetic Fentanyl Derivatives
			Desomorphine
			U-47700
			W-18 and W-15
			Ibogaine
		Opioid Tolerance, Dependence, and Addiction
		Pharmacotherapy for Opioid Overdose, Dependence, and Addiction
			Opioid Agonists
			Opioid Antagonists
		End of Chapter
			Chapter Review
			Key Terms
Part 3 Psychotherapeutic Drugs
	Chapter 11 Antipsychotic Drugs
		Schizophrenia
			Neurochemistry
			Dopamine Involvement
			Glutamate Involvement
			Serotonin Involvement
			Cannabinoid Involvement
			TAARS Involvement
		Historical Background and Classification of Antipsychotic Medications
		First-Generation Antipsychotics
			Pharmacokinetics
			Pharmacological Effects
			Negative Symptoms
			Side Effects and Toxicity
		Second-Generation Antipsychotics: Specific Agents
			Clozapine
			Aripiprazole
			Cariprazine
			Brexpiprazole
			Asenapine
			Lumateperone
		Prominent Side Effects of Selected Second-Generation Antipsychotics
			Clozapine
			Risperidone
			Olanzapine
			Quetiapine
			Ziprasidone
			Aripiprazole
			Paliperidone
			Iloperidone
			Cariprazine
			Brexpiprazole
			Asenapine
			Lurasidone
			Lumateperone
		Catie and Cutlass Studies
		Additional Uses for Second-Generation Antipsychotics
			Bipolar Disorder
			Treatment-Resistant Depression
			Dementia
			Autism Spectrum Disorders, Agitation, and Aggression
			Posttraumatic Stress Disorder
			Obsessive-Compulsive Disorder
			Borderline Personality Disorder
			Parkinson’s Disease
		The Art of Prescribing Antipsychotic Medications
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 12 Antidepressant Drugs
		Depression
			Pathophysiology of Depression
			Evolution of Antidepressant Drug Development
		First-Generation Antidepressants
			Tricyclic Antidepressants
			Monoamine Oxidase Inhibitors
		Atypical Antidepressants
		Selective Serotonin Reuptake Inhibitors
			The Treatment-Resistant Patient
			Serotonin Syndrome
			Discontinuation Syndrome
			SSRI-Induced Sexual Dysfunction
			Additional Side Effects of SSRIs
			Specific SSRIs
		Norepinephrine-Dopamine Reuptake Inhibitors
		Serotonin-Norepinephrine Reuptake Inhibitors
			Venlafaxine
			Desvenlafaxine
			Duloxetine
			Levomilnacipran
		Serotonin-2 Antagonist/Reuptake Inhibitor
		Noradrenergic/Specific Serotonergic Antidepressant
		Other Atypical Antidepressants
			Vilazodone
			Vortioxetine
			Brexpiprazole
		Comparative Studies
			STAR*D Study
			CO-MED Study
		Noncatecholamine Antidepressants
			Agomelatine
			Seltorexant
			Brexanolone
			Zuranolone
			Buprenorphine/Samidorphan
			Dextromethorphan/Buprenorphine
			REL-1017 (Esmethadone or Dextromethadone)
			Ketamine
			Psilocybin
			LSD
			Nitrous Oxide
		Additional and Alternative Approaches to Treatment-Resistant Depression
			Augmentation
			Complementary and Alternative Medicine Approaches
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 13 Sedative-Hypnotic Drugs: Treatment of Anxiety, Insomnia, and Epilepsy; Induction of Anesthesia
		History and Epidemiology
			Blackouts
			Dysfunctions Associated with Loss of Nerve Cell Function
			Complex Sleep-Related Behaviors
		Sites and Mechanisms of Action
		Barbiturates
			Pharmacokinetics
			Pharmacological Effects
			Psychological Effects
			Clinical Uses
			Adverse Effects
			Tolerance, Dependence, and Withdrawal
		Nonbarbiturates, Except Benzodiazepines
			Paraldehyde
			Chloral Hydrate
			Meprobamate and Carisoprodol
			Methaqualone
			Gamma Hydroxybutyrate
		Benzodiazepines
			Pharmacokinetics
			Pharmacological Effects
			Use and Misuse
		Alternatives to Benzodiazepines for the Treatment of Anxiety
			Antidepressants
			Anticonvulsants
			Noradrenaline Receptor Antagonists
			Melatonin Receptor Agonist
		Drugs Primarily Indicated for the Treatment of Insomnia
			Nonbenzodiazepine Agonists at Benzodiazepine Receptors
			Melatonin Receptor Agonists
			Orexin Receptor Antagonists
			Histamine Receptor Antagonist
		Off-Label and Alternative Treatments for Insomnia
		Anticonvulsant Drugs
			Drugs Approved Before 1993
			Drugs Approved 1993–2005
			Drugs Approved 2006–2019
			Effects in Pregnancy
			Risk of Suicidality
			Therapeutic Drug Monitoring with Anticonvulsants
		General Anesthetics
		End of Chapter
			Chapter Review
			Key Terms
	Chapter 14 Drugs Used to Treat Bipolar Disorder
		Diagnostic and Treatment Issues
			Overview of Pharmacotherapy
			Pathophysiology and Mechanisms of Drug Action
			STEP-BD Study
		Lithium
			Pharmacokinetics and Pharmacodynamics
			Side Effects and Toxicity
			Effects in Pregnancy
			Nonadherence
			Combination Therapy
		Mood Stabilizers: Antiepileptic Drugs
			Carbamazepine
			Oxcarbazepine
			Valproic Acid
			Lamotrigine
			Gabapentin and Pregabalin
			Topiramate
		Antipsychotic Drugs for Bipolar Disorder
			Acute Manic Episodes
			Bipolar Depression
			Acute Bipolar Agitation
			Relapse Prevention
			In the Pipeline
		Psychotherapeutic and Psychosocial Treatments
		End of Chapter
			Chapter Review
			Key Terms
Part 4 Special Populations
	Chapter 15 Pregnancy and Psychoactive Drugs
		Substance Abuse and Pregnancy
			Nicotine
			Alcohol
			Cannabis
			Stimulants
			Opioids
		Psychotherapeutic Drugs and Pregnancy
			Antidepressants
			Antipsychotics
			Stimulants
			Lithium and Anticonvulsants
			Benzodiazepines
		Summary and Conclusion
		End of Chapter
			Chapter Review
			Key Term
	Chapter 16 Child and Adolescent Psychopharmacology
		Substance Abuse in Children and Adolescents
			Common Addictive Substances
			Guidelines for Prevention, Diagnosis and Treatment of Substance Abuse in Children and Adolescents
		Mental Health Disorders in Children and Adolescents
		Treatment of Anxiety Disorders
			Obsessive-Compulsive Disorder
			Posttraumatic Stress Disorder
			Social Anxiety Disorder
		Treatment of Depression
			Antidepressant Medication
			Antidepressants and Suicidality
		Treatment with Antipsychotic Medications
		Treatment of Bipolar Disorder
			Lithium
			Anticonvulsants
		Treatment of Autism Spectrum Disorders
		Treatment of Behavioral Disorders Marked by Aggression
		Treatment with Analgesics
		Treatment of ADHD
			ADHD Medications
			ADHD and Specific Age Groups
			Side Effects of ADHD Medications
		End of Chapter
			Chapter Review
			Key Term
	Chapter 17 Geriatric Psychopharmacology
		Inappropriate Drug Use in Older Adults
		Agitation, Aggression, and Psychosis in Older Adults
		Depression in Older Adults
		Parkinson’s Disease
			Levodopa
			Alternatives to Levodopa Therapy
			Apathy
		Alzheimer’s Disease
			Medication Therapy
			Depression and Apathy
			Principles of Care
		End of Chapter
			Chapter Review
			Key Term
	Chapter 18 Challenging Times for Mental Health: The COVID-19 Pandemic and Beyond
		Lessons from the Pandemic
			Health Care Workers
			Children and Adolescents
			Adults
			Long-Haulers
		Moving Forward: Addressing Inequities and Providing Mental Health Support
			Inequities in Health and Health Care
			Mental Health Support
		Chapter Review
Appendix A
Appendix B
Glossary
References
Notes
Index
Extended Descriptions
	FIGURE 1.1 The fate of a drug in the body
	FIGURE 1.2 Theoretical blood levels of triazolam and lorazepam following oral administration
	FIGURE 1.3 The hepatic portal connection between the gastrointestinal tract and the liver
	FIGURE 1.4 Heart and circulatory system
	FIGURE 1.5 A cell membrane
	FIGURE 1.6 A typical capillary cell
	FIGURE 1.7 The blood-brain barrier
	FIGURE 1.8 Drug metabolism by the major hepatic C Y P enzymes
	FIGURE 1.9 A nephron
	FIGURE 1.10 Redistribution and half-life of a drug
	FIGURE 1.11 Steady-state concentration
	FIGURE 2.1 The Human Brain
	FIGURE 2.2 Brain Stem and Cerebellum
	FIGURE 2.3 Thalamus and Hypothalamus
	FIGURE 2.4 Basal Ganglia
	FIGURE 2.5 Limbic System and Reward Circuit
	FIGURE 2.6 Cerebral Cortex
	FIGURE 2.8 A Typical Neuron
	FIGURE 2.9 A Typical Synapse
	FIGURE 2.10 Acetylcholine in the Brain
	FIGURE 2.11 An Acetylcholine Synapse
	FIGURE 2.12 Catecholamines: Structure and Biosynthesis
	FIGURE 2.13 Norepinephrine in the Brain and Spinal Cord
	FIGURE 2.14 Dopamine in the Brain
	FIGURE 2.15 Serotonin in the Brain
	FIGURE 2.16 Serotonin (5-H T) Receptors
	FIGURE 2.17 A Glutamate Synapse
	FIGURE 2.18 A GABA Synapse
	FIGURE 3.2 An Ionotropic Receptor
	FIGURE 3.3 Drug and Neurotransmitter Binding Sites on an Ionotropic Receptor
	FIGURE 3.4 A G-Protein-Coupled Receptor
	FIGURE 3.5 Activation of an Ionotropic Receptor by a G-Protein-Coupled Receptor
	FIGURE 3.6 Second Messengers
	FIGURE 3.7 Downregulation and Upregulation
	FIGURE 3.8 A Dose-Response Curve
	FIGURE 3.9 Dose-Response Curves: Slope, Potency, and Efficacy
	FIGURE 3.10 Dose-Response Curves: Full Agonists, Partial Agonists, and Antagonists
	FIGURE 3.11 Dose-Response Curves: Agonists in the Presence of Antagonists
	FIGURE 3.12 Therapeutic Index
	FIGURE 4.1 The Mesolimbic Dopamine Pathway
	Decreased Dopamine Receptor Availability in Addicted Brains
	FIGURE 4.3 Factors Associated with Relapse
	FIGURE 4.4 Glutamate and the Craving for Drugs
	FIGURE 5.2 Metabolism of Ethanol
	FIGURE 5.3 Elimination Rate of Ethanol
	FIGURE 5.4 Probability of Blackouts
	FIGURE 6.1 Structure of Caffeine and Three End Products of Caffeine Metabolism
	FIGURE 6.2 Structure of Adenosine
	FIGURE 6.3 Blood Nicotine Concentrations During and After Use of Four Different Products
	FIGURE 6.4 Current and Former Smokers, 1965 to 2017
	Advertisement of Cigarette
	FIGURE 6.5 How Varenicline Works
	FIGURE 7.1 Cocaine Metabolism
	FIGURE 7.2 Dopamine Reuptake and Cocaine
	FIGURE 7.3 Phenylethylamine: The Basic Sympathomimetic Amine Nucleus
	Advertisement of Methedrine
	FIGURE 7.4 Dopamine Reuptake and Amphetamines
	FIGURE 7.5 Structures of Some Synthetic Cathinones
	FIGURE 7.6 Structures of Methylphenidate, Modafinil, and Armodafinil
	FIGURE 8.1 Structures of Dopamine, Norepinephrine, Amphetamine, and Ten Structurally Related Psychedelic Drugs
	FIGURE 8.2 Structures of B Z P and T F M P P
	FIGURE 8.3 Structures of Serotonin and Ten Serotoninlike Psychedelic Drugs
	FIGURE 8.4 Structures of Acetylcholine and Scopolamine
	FIGURE 8.5 Structures of Phencyclidine and Ketamine
	FIGURE 8.6 Structure of Salvinorin A
	FIGURE 9.1 Structures of T H C, C B D, and Anandamide
	FIGURE 9.2 Increasing Ratio of T H C to T B D
	FIGURE 9.4 C B D Concentration in Urine over Time
	FIGURE 9.5 Benzodiazepines Use Declines with Cannabis Use
	FIGURE 10.2 Overdose deaths involving opioids, 19 99 to 20 20
	FIGURE 10.3 Overdose deaths involving heroin, 19 99 to 20 20
	FIGURE 10.4 Overdose deaths involving benzodiazepines, 19 99 to 20 20
	FIGURE 10.5 Pain transmission
	FIGURE 10.6 An opioid mu receptor
	FIGURE 10.7 Morphine in the brain
	FIGURE 10.8 Pain relief with cebranopadol
	FIGURE 10.9 Opioid use disorder treated with naltrexone or buprenorphine
	FIGURE 10.10 Plasma concentrations of naloxone
	FIGURE 11.1 Dopamine receptor blockage and clinical dose of antipsychotic drugs
	FIGURE 11.2 Weight gain with antipsychotic drugs
	FIGURE 12.1 Efficacy of antidepressant medication and depression severity
	FIGURE 12.2 Hippocampal neurons in health and disease
	FIGURE 12.3 Signs and symptoms of the serotonin syndrome
	FIGURE 12.4 Suicidal risk decreases with time in patients receiving fluoxetine or venlafaxine
	FIGURE 12.5 Effect of ketamine infusions on depression severity in treatment-resistant major depression
	FIGURE 12.6 Efficacy of aripiprazole in treating depression
	FIGURE 13.1 Interactions of sedative-hypnotic drugs with G A B A subscript A receptors
	FIGURE 13.2 Chemical structures of barbiturates
	FIGURE 13.3 Chemical structures of nonbarbiturates
	FIGURE 13.4 Adults receiving benzodiazepine prescriptions, 19 96 to 2013
	FIGURE 13.5 Chemical structures of benzodiazepines
	FIGURE 13.6 Metabolism of benzodiazepines
	FIGURE 13.7 Chemical structures of zolpidem, zaleplon, and eszopiclone
	FIGURE 13.8 Chemical structures of anticonvulsant drugs
	FIGURE 13.9 Suicidality rate
	FIGURE 14.1 Bipolar 1 disorder
	FIGURE 14.2 Self-harm rates
	FIGURE 15.1 Opioid use disorder in U.S. pregnant women
	FIGURE 16.1 Prevalence of e-cigarettes
	FIGURE 16.2 Illegal drug use in the past year among 12th graders
	FIGURE 16.3 Illicit use of prescription and over-the-counter drugs in the past year among 12th graders
	FIGURE 16.4 Major depressive episodes
	FIGURE 16.5 Y M R S summary score
	FIGURE 17.1 Parkinson’s disease therapy
	FIGURE 17.2 Synthesis of dopamine from tyrosine
	FIGURE 17.3 The “on-off” phenomenon with levodopa
	Deaths due to Alzheimer’s disease in the U.S
	FIGURE 18.1 Prevalence of depression symptoms in U.S. adults, before vs. during the COVID-19 pandemic
	FIGURE 18.2 Mental illness and substance use disorders in U.S. adults aged 18 or older, 2018
	FIGURE 18.3 Maslow’s hierarchy of needs
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