Pharmacokinetic mechanisms of ethanol-psychotropic drug interactions.
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.
D000437:Alcoholism / Q000378:metabolism; D001711:Biotransformation; D004333:Drug Administration Routes; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D011485:Protein Binding; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000378:metabolism
D011619:Psychotropic Drugs; D000431:Ethanol