PSYCHOTROPIC DRUGS. Norman L. Keltner, RN, CRNP, EdD. David G. Folks, MD
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1 PSYCHOTROPIC DRUGS Norman L. Keltner, RN, CRNP, EdD Associate Professor School of Nursing University of Alabama at Birmingham Birminghanij Alabama David G. Folks, MD Professor and Chair Creighton University Medical Center School of Medicine University of Nebraska Medical Center College of Medicine Department of Psychiatry Omaha, Nebraska Second Edition with 40 illustrations St. Louis Baltimore Boston Carlsbad Chicago Naples New York Philadelphia Portland London Madrid Mexico City Singapore Sydney Tokyo Toronto Wiesbaden
2 PART ONE CLINICAL PSYCHOPHARMACOLOGY, 1 UNIT 1 Introduction to Psychotropic Drug Use, 3 1 Psychiatric Care and Contemporary Treatment, 4 Benchmarks in Psychiatric Care: The Road From Confinement to Community, 5 Period of Enlightenment (Caring), 5 Period of Scientific Study (Curing), 6 Period of Psychotropic Drugs (Chemicals), 6 Period of Community Mental Health Care (Community), 8 Remarks, 8 2 Neurb anatomy, 10 Richard A. Sugerman F. Cleveland Kinney Central Nervous System, 10 Telencephalon (Cerebrum), 10 Diencephalon (Thalamic Nuclei), 10 Brain Stem, Cerebellum, Reticular Formation, and Spinal Cord, 14 Peripheral Nervous System, 18 Autonomic Nervous System, 18 Supraspinal Motor Pathways, 20 Basal Ganglia, 22 Limbic Lobe, 25 3 Neuropharmacology and Psychotropic Drugs, 28 Richard A. Sugerman Synaptic Transmission, 28 Types of Synapses, 30 Membrane Receptors, 30 Mechanisms of Receptor Action, 31 Neurotransmission, 31 Neuron Excitation and Inhibition, 31 Denning Neurotransmitters, 31 Action and Synthesis of Neurotransmitters, 31 Cholinergic System, 33 Monoamine Systems, 33 Neuropeptides, 35 Amino Acid Transmitters, 37 Neurotransmitters and Neurochemistry of Behavior, 39
3 xvi xvii \ UNIT II Drugs Used in the Treatment of Mental Disorders, 45 4 Schizophrenia and Other Psychoses, 46 Historical Considerations, 46 DSM-IV Terminology and Criteria, 47 Antipsychotic Drugs, 49 History, 52 Three Classification Systems: Molecular, Potency,Typicality, 52 Neurochemical Theory of Schizophrenia, 53 Pharmacologic Effects (Therapeutic Effects), 54 Psychiatric Symptoms Modified by Antipsychotic Drugs, 55 Other Uses and Effects, 56 Pharmacokinetics, 56 Side Effects, 59 Implications, 66 Chemical Class and Structure of Specific Drugs, 68 Atypical Antipsychotics or Serotonin/Dopamine Antagonists (SDAs), 71 Drugs in the Evaluation Phase, 76 Remarks, 76 5 Mood Disorders, 80 Historical Considerations, 80 Scope of the Problem, 80 Diagnostic Considerations, 81 Major Depression, 82 Bipolar Disorder, 83 Suicide and Other Risks, 83 Diagnostic Dilemmas, 83 Treatment Considerations, 84 Depression, 84 Bipolar Disorder, 84 Other Mood Disorders, 84 Antidepressants, 85 Historical Considerations, 85 Neurochemical Theory of Effectiveness, 86 Tricyclic, Heterocyclic, and Second-Generation Antidepressants, 90 Pharmacokinetics, 90 Side Effects, 91 Implications, 91 Specific Tricyclic Antidepressants, 95 Newer Antidepressant Agents, 96 Venlafaxine, 99 Bupropion, 102 Nefazodone, 102 Other New Antidepressants, 103 Monoamine Oxidase Inhibitors, 103 Pharmacokinetics, 106 Side Effects, 106 Specific Interactions, 107 Implications, 108 Specific Monoamine Oxidase Inhibitors, 110 Treatment Issues and Caveats, 111 Antimanic and Mood-Stabilizing Drugs, 113 Lithium, 113 Pharmacokinetics, 114 Side Effects, 115 Implications, 117 Alternative Antimanic and Mood-Stabilizing Drugs, 118 Valproic Acid, 118 Carbamazepine, 123 Benzodiazepines, 125 Miscellaneous Agents, Anxiety Disorders, Historical Considerations, 129 Diagnostic Considerations, 132 Anticipatory Anxiety, 132 Posttraumatic Stress Disorder, 132 Mixed Anxiety-Depression, 134 Generalized Anxiety, 134 Nonpsychiatric Anxiety, 135 Treatment, 135 Anxiolytics, 137 Benzodiazepines, 137 Pharmacologic Effect, 137 Pharmacokinetics, 140 Side Effects, 141 Implications, 141 Buspirone, 144 Pharmacokinetics, 144 Implications, 145 Specific Anxiety Disorders and Mixed Syndromes, 146 Panic Disorder, 146 Treatment, 147 Phobic Disorders, 149 Treatment, 149 Obsessive-Compulsive Disorder, 150 Treatment, 151 Seizure Disorders, 156 Epilepsy, 156 Categories of Seizures, 156 Antiepileptic Drugs, 160 Hydantoins: Prototype Drug, Phenytoin, 163 Pharmacologic Effects, 163 Pharmacokinetics, 164 Side Effects, 169 Implications, 170 Related Hydantoins, 173 Long-Acting Barbiturates: Prototype Drug, Phenobarbital, 173 Pharmacologic Effects, 173
4 xviii xix Pharmacokinetics, 173 Side Effects, 174 " Implications, 175 Related Barbiturates, 176 Succinimides: Prototype Drug, Ethosuximide, 177 Pharmacologic Effects, 177 Pharmacokinetics, 177 Side Effects, 177 Implications, 178 Related Succinimides, 178 ^ Oxazolidinediones: Prototype Drug, Trimethadione, 179 Pharmacologic Effects, 179 Pharmacokinetics, 179 Side Effects, 179 Implications, 179 Related Oxazolidinedione, 180 Benzodiazepines: Diazepam, Clonazepam, Clorazepate, 180 Diazepam Indication: Treating Status Epilepticus, 181 Clonazepam Indication: Lennox-Gastaut, 181 Clorazepate Indication: Partial Seizures, 182 Other Antiepileptics, 182 Carbamazepine, 182 Pharmacologic Effect, 182 Pharmacokinetics, 182 Side Effects, 183 Implications, 183 Valproic Acid and Derivatives, 184 Pharmacologic Effects, 184 Pharmacokinetics, 185 Side Effects, 185 Implications, 185 Related Drugs, 186 Gabapentin, 186 Lamotrigine, 187 Less Frequently Used Antiepileptics, 187 Acetazolamide, 187 Lidocaine, 187 Magnesium sulfate, 187 Paraldehyde, 187 Antiepileptics with Severe or Dangerous Side Effects, 188 Phenacemide, 188 Felbamate, 188 Agents Pending Approval by the FDA, Sleep Disorders, 190 Historical Considerations, 190 Diagnostic Considerations, 191 Drugs Used to Treat Insomnia, 194 Neurochemical Effects of Hypnotics, 197 Benzodiazepines, 198 Pharmacologic Effects, 198 Pharmacokinetics, 201 Side Effects, 206 Implications, 208 Specific Benzodiazepines, 209 Nonbenzodiazepine Hypnotic: Zolpidem, 210 Treatment Considerations, 211 Other Drugs Used to Treat Insomnia, 212 Discussion, 213 Other Sleep Disorders, 214 Hypersomnia, 214 Narcolepsy, 215 Sleep Apnea, 218 Parasomnias, 218 < Periodic Leg Movements (Restless Leg Syndrome), 218 Comorbid Conditions, Acute Psychoses and the Violent Patient, 223 Scope of the Problem, 223 The Clinical Approach, 223 Policies on Violence, 224 Diagnostic Considerations, 224 Assessment and Clinical Approach, 224 Drug Treatment, 227 Short-Term Treatment, 227 Long-Term Treatment, 233 Implications and Treatment Issues, Alcoholism and Other Substance Abuse Disorders, 240 Scope of the Problem, 240 Epidemiology, 240 Historical Perspective, 240 National Surveys, 241 Pregnancy Considerations, 242 Psychologic Considerations, 242 Genetic, Environmental, and Other Influences, 243 Genetic Influences, 243 Environmental Influences, 243 Psychiatric Influences, 244 Drug-Related Influences, 244 Neurobiologic Influences, 245 Diagnostic Considerations, 245 American Psychiatric Considerations, 246 Comorbidity, 246 Drug Treatment, 248 Short-Term Treatment Objectives, 248 Long-Term Treatment Objectives, 248 Drugs Used in the Treatment of Alcoholism, 249 Drugs Used to Treat Narcotic (Opioid) Dependence and Abuse, 251 Drugs Used to Treat Effects of Central Nervous System Stimulants, 253 Drugs Used to Treat Nicotine Dependence, 257
5 XX xxi Drugs Used to Treat Cannabis (Marijuana) Dependence, 260 Drugs Used to Treat Abuse of Phencyclidine and Similar Agents, 260 Drugs Used to Treat Sedative-Hypnotic and Anxiolytic Abuse and Dependence, 260 UNIT III Drug Issues Related to Psychopharmacology, Drugs Used for Electroconvulsive Therapy, 268 A Summative History ofect, 268 \ Historical Perspective on the Negative View, 269 Modern Electroconvulsive Therapy, 270 Indications, 270 Contraindications, 273 AdvantageSj 274 Disadvantages, 276 How Electroconvulsive Therapy Works, 276 Drugs Used in Electroconvulsive Therapy, 276 Succinylcholine, 277 Pharmacokinetics and Interactions, 277 Methohexital, 277 Pharmacokinetics, 278 Side Effects, 278 Interactions, 278 Atropine, 278 Pharmacokinetics, 278 Side Effects, 279 Interactions, Drugs of Abuse, 281 Leland N. Allen III Alcohol, 283 Etiologic Theories, 286 Pharmacokinetics, 287 Physiologic Effects, 289 Related Issues, 290 Other Central Nervous System Depressants, 292 Barbiturates, 292 Pharmacokinetics, 293 Physiologic Effects, 293 Related Issues, 293 Inhalants, 294 Narcotics (Opioids), 294 Pharmacokinetics, 295 Physiologic Effects, 295 Related Issues, 295 Specific Drugs, 296 Stimulants, 297 Cocaine, 297 Pharmacokinetics, 298 Physiologic Effects, 298 Amphetamines, 299 Pharmacokinetics, 299 Physiologic Effects, 299 Related Issues, 299 Hallucinogens, 300 Mescaline and Related Synthetic Substances, 301 Pharmacokinetics, 301 Physiologic Effects, 301 Psilocybin, Psilocin, 301 Pharmacokinetics, 301 Physiologic Effects, 301 Marijuana, 302 Pharmacokinetics, 302 / Physiologic Effects, 302 Lysergic Acid Diethylamide, 302 Pharmacokinetics, 302 Physiologic Effects, 303 Phencyclidine, 303 Pharmacokinetics, 303 Physiologic Effects, 303 Related Issues, 303 Remarks, Drugs Used to Stimulate the Central Nervous System, 308 Cerebral Stimulants, 308 Amphetamines, 308 Pharmacologic Effect, 309 Pharmacokinetics, 311 Side Effects, 311 Implications, 312 Other Prescription Central Nervous System Stimulants, 315 Methylphenidate, 315 Pharmacokinetics, 315 Side Effects, 316 Implications, 316 Pemoline, 316 Other Stimulants: Caffeine and Amphetamine-Like Anorectics, 317 Caffeine, 317 Phenylpropanolamine, 318 Treatment Considerations, 321 Treatment of Depression, 321 Treatment of Depressed Medically 111 Patients, 321 Use as a Challenge Test for Predicting a Response to Antidepressants, 322 Use in Elderly Persons, 322 Caffeine Augmentation of Electroconvulsive Therapy, 322 Treatment of Schizophrenia, 322 Miscellaneous Uses, 322 '
6 xxii 14 Drugs Used to Treat Extrapyramidal Side Effects, 325 Review of Parkinsonism, 325 Extrapyramidal Side Effects, 331 Drugs Used to Treat Parkinsonism, 332 Anticholinergic (Antiparkinson) Agents, 336 Pharmacologic Effects, 338 Side Effects, 338 Implications, 340 Patient Education, 341 Related Anticholinergic Drugs, 342 * Benztropine, 342 Biperiden, 342 Ethopropazine, 342 Procyclidine, 342 Diphenhydramine, 342 Issues in Anticholinergic Drug Administration, 343 Other Agents, 345 Benzodiazepines: Treatment of EPSEs, 345 Beta-Adrenergic Antagonists: Treatment of EPSEs, 345 Clonidine: Treatment of EPSEs, 345 Nifedipine and Verapamil: Treatment oftardive Dyskinesia, 345 Dantrolene: Treatment of Neuroleptic Malignant Syndrome, 345 UNIT IV Developmental Issues Related to Psychotropic Drugs, Psychopharmacology for Children, 350 Lawrence Scahill Scope of the Problem, 350 General Principles, 350 Psychotropic Medications Used with Children, 353 Stimulants, 353 Indications, 353 Empirical Support, 353 Mechanism of Action, 353 Clinical Management, 354 Side Effects of Central Nervous System Stimulants, 355 Toxic Effects, 355 Substance Abuse, 355 Antidepressants, 355 Indications, 355 Tricyclic Antidepressants, 356 Empirical Support, 356 Mechanism of Action, 357 Pharmacokinetics, 357 Clinical Management, 357 Side Effects, 358 Interactions, 358 Toxic Effects, 358 Selective Serotonin Reuptake Inhibitors, 358 Indications, 359 Obsessive-Compulsive Disorder, 359 Empirical Support, 359 i Mechanism of Action, 359 Pharmacokinetics, 360 Clinical Management, 360 Withdrawal of SSRIs and Duration of Therapy, 361 Augmentation Strategies, 361 SSRIs and Depression, 362 Other Antidepressant Medications, 362 Antipsychotic Drugs, 362 Indications, 362 Mechanism of Action, 364 Pharmacokinetics, 364 Clinical Management and Empirical Support, 364 Side Effects, 366 Toxic Effects, 367 Tardive Dyskinesia, 367 Lithium, 367 Indications, 367 Empirical Support, 367 Clinical Management, 368 Side Effects, 368 Alpha-2 Adrenergic Agents, 368 Indications, 368 Empirical Support, 368 Mechanism of Action, 368 Clinical Management, 369 Other Agents Used in the Treatment of Children with Psychiatric Disorders, Psychopharmacology for Adolescents, 374 Lawrence Scahill Scope of the Problem, 374 General Principles of Adolescent Psychopharmacology, 374 Strategies for Effective Administration, 374 Other Issues of Administration, 375 Psychotropic Medications Used with Adolescents, 376 Stimulants, 376 Indications, 376 Empirical Support, 376 Mechanism of Action, 377 Clinical Management, 377 Antidepressants, 378 Indications, 378 Empirical Support, 378 Mechanism of Action, 379 Clinical Management, 379 Antipsychotics, 380 Indications, 380 Empirical Support, 381 Mechanism of Action, 381 Clinical Management, 381 xxm
7 xxiv Lithium, 382 Indications, 382 Empirical Support, 384 Mechanism of Action, 384 Clinical Management, 384 Other Drugs Used in the Treatment of Bipolar Disorder, 385 Carbamazepine (Tegretol), 385 Valproate (Depakote), 386 Drugs Used in the Treatment of Aggressive Behavior, 386 Neuroleptics, 387 Lithium, 387 Anticonvulsants, 387 Alpha-2 Adrenergic Agents Tic Disorders, 387 Use of Combined Drug Therapies, Psychopharmacology for Elderly Persons, 391 Scope of the Problem, 391 General Factors Pertinent to Psychotropic Drug Therapy, 392 Pharmacokinetics, 394 Pharmacodynamics, 397 Drug Reactions, 398 Compliance, 399 Psychiatric Disturbances Prevalent in Late Life, 399 Mood Disorders, 399 Psychotic Disorders, 401 Anxiety Disorders and Acute Insomnia, 402 Mixed Anxiety-Depression, 404 ( Agitation and Aggression, 404 Delirium, "Sundowning," and Confusion Associated with Dementia, 405 Alzheimer's Disease and Related Disorders, 408 Management of Delirium, Dementia, and Alzheimer's Disease, 412 Supportive Care, 412 Drug Therapy Options, 413 Remarks, 416 PART TWO PSYCHOTROPIC DRUG PROFILES, 423 APPENDIX, 532 GENERAL INDEX, 535 DISORDERS INDEX, 562 DRUG INDEX, 567
Psychotropic Drugs 0, 4-
0, 4- } -v Psychotropic Drugs NORMAN L. KELTNER, Ed D, RN Associate Professor, Graduate Program, University of Alabama School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama DAVID
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