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Chapter 38 Drug Abuse II: Alcohol Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alcohol Most commonly used and abused psychoactive agent in the United States Some therapeutic use Primarily used for nonmedical purposes Moderate consumption: prolongs life, reduces risk of dementia and cardiovascular disorders Excessive consumption: diminishes quality and quantity of life Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 2 Basic Pharmacology of Alcohol Central nervous system effects Acute effects • General depression of CNS function Enhances GABA-mediated inhibition Dose-dependent Binds with 5-HT3 receptors • Activation of the reward circuit Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 Basic Pharmacology of Alcohol Chronic effects Two neuropsychiatric syndromes • Wernicke’s encephalopathy • Korsakoff’s psychosis Impact on cognitive function Effect on sleep Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 4 Basic Pharmacology of Alcohol Other pharmacologic effects Cardiovascular system Respiration Liver Stomach Kidney Pancreas Sexual function Cancer: breast and colorectal cancer Pregnancy and lactation Impact on longevity Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 5 Basic Pharmacology of Alcohol Pharmacokinetics Absorption Distribution Metabolism Blood levels Tolerance Physical dependence Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 6 Basic Pharmacology of Alcohol Drug interactions CNS depressants Nonsteroidal anti-inflammatory drugs Acetaminophen Disulfiram Antihypertensive drugs Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 7 Basic Pharmacology of Alcohol Acute overdose Vomiting, coma, pronounced hypotension and respiratory depression Therapeutic uses Topical Oral Intravenous • Replacement of calories and fluid Local injection • Nerve block Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 8 Alcohol Use Disorder Relapsing disorder Impaired control over drinking Preoccupation with alcohol consumption Use of alcohol despite awareness of adverse consequences Distortions in thinking Influenced by genetics and psychosocial and environmental factors Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 9 Drugs for Alcohol Use Disorder Drugs used to facilitate withdrawal Drugs used to maintain abstinence Other drugs used in the treatment of alcohol abuse Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 10 Drugs Used to Facilitate Withdrawal Benzodiazepines Chlordiazepoxide (Librium, others) Diazepam (Valium) Oxazepam (Serax) Lorazepam (Ativan) Adjuncts to benzodiazepines Carbamazepine (antiepileptic drug) Clonidine (alpha-adrenergic blocker) Atenolol and propranolol (beta-adrenergic blockers) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 11 Drugs Used to Maintain Abstinence Disulfiram aversion therapy Refrain from drinking Causes irreversible inhibition of aldehyde dehydrogenase Effects caused by alcohol plus disulfiram are referred to as acetaldehyde syndrome Patients must be carefully chosen Patients must be thoroughly informed to avoid all forms of alcohol • Sauces, cough syrups • Alcohol applied to the skin (lotions, colognes, liniments) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 12 Fig. 38–1. Ethanol metabolism and the effect of disulfiram. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 13 Drugs Used to Maintain Abstinence Naltrexone (Revia) Pure opioid antagonist Decreases craving for alcohol Blocks reinforcing effects of alcohol Mechanism unclear Adverse effects • Nausea • Headache Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 14 Drugs Used to Maintain Abstinence Acamprosate (Campral) Reduces unpleasant feelings brought on by abstinence Devoid of direct anxiolytic, anticonvulsant, and antidepressant activity Does not cause alcohol aversion Administered orally Excreted unchanged in the urine Adverse effects and drug interactions • Diarrhea • Avoid during pregnancy Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 15 Drugs Used to Maintain Abstinence Topiramate (Topamax) Reduces craving for alcohol Ondansetron (Zofran) Selective 5-HT3 receptor antagonist Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 16 Nutritional Support, Fluid Replacement, and Antibiotics B vitamins Thiamine Folic acid Cyanocobalamin Vitamin supplements Fluid replacement therapy Antibiotics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 17