Biomaterial Database

Pharmacokinetic mechanisms of ethanol-psychotropic drug interactions. 1986

D A Ciraulo, and J Barnhill

Acute and chronic ethanol consumption alters psychotropic drug pharmacokinetics. An understanding of the processes of drug absorption, distribution, biotransformation, and elimination provide a rational basis for predicting and evaluating drug interactions. Careful application of clinical pharmacokinetic models describing these physiological processes are particularly appropriate for the task of understanding drug and alcohol interactions. Absorption: Acute alcohol inhibits first-pass effect increasing systemic bioavailability. Ethanol inhibits gastric emptying and may delay drug absorption (increase lag time of absorption) and decrease the rate of absorption. The effects of chronic alcohol intake are unknown. Distribution: Hypoalbuminemia may be present in alcoholics with liver disease. Fluctuations in free fractions of drugs may occur in the alcohol withdrawal period. The clinical effects of protein binding changes are dependent on degree of binding, hepatic extraction ratio, and binding protein. Acute low-dose ethanol increases hepatic blood flow while high doses decrease it. The effects of chronic alcohol intake on liver blood flow are unknown. Hepatic blood flow changes show the greatest effects on drugs with high extraction ratios. Metabolism: Acute alcohol ingestion usually inhibits drug metabolism and chronic intake (in the absence of severe liver disease) enhances metabolism. Cirrhosis impairs oxidative metabolism, but spares glucuronidation. Although these generalizations may serve as useful guidelines for predicting alcohol and psychotropic drug interactions, they should be applied with caution as exceptions do exist.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011619	Psychotropic Drugs	A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents).	Psychoactive Agent,Psychoactive Agents,Psychoactive Drug,Psychopharmaceutical,Psychopharmaceuticals,Psychotropic Drug,Psychoactive Drugs,Agent, Psychoactive,Agents, Psychoactive,Drug, Psychoactive,Drug, Psychotropic,Drugs, Psychoactive,Drugs, Psychotropic
D004333	Drug Administration Routes	The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue.	Administration Routes, Drug,Administration Route, Drug,Drug Administration Route,Route, Drug Administration,Routes, Drug Administration
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000437	Alcoholism	A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)	Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.