Alcoholdrug Interactions

Alcohol-drug interactions are complex. The consequences of using alcohol and drugs together vary with the dosage of the drug; the amount of alcohol consumed; the mode of administering the drug (oral, intravenous, intramuscular, etc.); and the nature of the drug (anticonvulsant, vasodilator, analgesic, etc.). The alcohol may alter the effects of the drug; the drug may change the effects of alcohol; or both may occur.

Alcohol-drug interactions are most important with drugs that have a steep DOSE-RESPONSE CURVE and a small therapeutic ratio—so that small quantitative changes at the target site of action lead to significant changes in drug action. In alcoholics, changes in susceptibility to drugs are due to changes in their rates of metabolism (pharmacokinetics) and the adaptive and synergistic effects on their organs, such as the central nervous system (pharmacodynamics). The clinical interactions of alcohol and drugs often appear paradoxical: Sensitivity to many drugs, especially sedatives and tranquilizers, is strikingly increased when alcohol is present at the same time; however, alcoholics, when abstinent, are tolerant to many drugs. These acute and chronic actions of alcohol have been attributed, respectively, to additive and adaptive responses in the central nervous system (phar-macodynamic interactions).

It is now recognized that alcohol can also interact with the cytochrome P450 drug-metabolizing system, binding to P450, being oxidized to acetal-dehyde by P450, increasing the content of P450, and inducing (causing an increase in the activity of) a unique isozyme of P450. Inhibition of drug oxidation when alcohol is present at the active site of P450 is due to displacement of the drug by alcohol and competition for metabolism; this increases the half-life and circulating concentration of drugs. Induction of P450 by chronic-alcohol treatment can result in the increased metabolism of drugs, as long as alcohol is not present to compete for oxidation. These pharmacokinetic interactions may contribute to either increased sensitivity or the tolerance observed with alcohol-drug interactions.

Alcohol can affect drug pharmacokinetics by altering drug absorption from the alimentary tract. For example, diazepam (Valium) absorption is enhanced by the effects of alcohol on gastric emptying. Alcohol placed in the stomach at concentrations of 1 percent to 10 percent increases the absorption of pentobarbital, PHENOBARBITAL, and theophylline, whereas drugs such as DlSULFIRAM and CAFFEINE decrease alcohol absorption by decreasing gastric emptying. Cimetidine (Tagamet)—a drug used to treat stomach ulcers— increases blood alcohol concentrations by inhibiting ADH in the stomach and first-pass metabolism of alcohol. Binding of a drug to plasma proteins will change the effective therapeutic level of the drug, because when the drug is linked to the proteins, it is not available to act on the tissue. Alcohol itself and alcohol-induced liver disease cause a decreased synthesis and release of such plasma proteins as albumin. The resulting hypoproteinemia can result in decreased plasma-protein binding of such drugs as quinidine (Quinidex), dapsone (DDS), triamterene (Dyrenium), and fluorescein (Fluo-rescite). Alcohol may also directly displace drugs from plasma proteins.

The effects of alcohol on blood flow in the liver are controversial, although most recent reports suggest an increase; this could be significant with respect to metabolism of flow-limited drugs. At higher concentrations, alcohol can act as an organic solvent and "fluidize" cellular membranes, which may increase the uptake or diffusion of drugs into the cell.

Drug Addiction

Drug Addiction

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