Metabolism

Many alcohol-drug interactions occur at the level of actual metabolism. Ethanol (ethyl alcohol—common in wines and liquors) will compete with such other alcohols as METHANOL (methyl alcohol—called wood alcohol) or ethylene glycol (antifreeze), for oxidation via alcohol dehydroge-nase. In fact, treatment against poisoning by methanol or ethylene glycol involves the administration of ethanol—as the competitive inhibitor—or the addition of inhibitors of alcohol dehydrogenase such as pyrazole or 4-methylpyrazole.

As discussed above, the presence of alcohol will inhibit the oxidation of drugs by cytochrome P450.

Alcohol has been shown to inhibit oxidation of such representative drugs as aniline, pentobarbital (Nembutal), benzphetamine (Didrex), benzpyrene, aminopyrine, ethylmorphine, METHADONE, meprobamate (Equanil, Miltown), phenytoin (Dilantin), propranolol (Inderal), caffeine, tolbutamide (Orinase), warfarin (Coumadin), phenothi-azine, BENZODIAZEPINE, CHLORDIAZEPOXIDE, amitriptyline (Elavil), chlormethiazole, chlorpro-mazine (Thorazine), isoniazid (INH), imipramine (Tofranil), dextropropoxyphene, triazolam (Halcion), industrial solvents, and acetaminophen (Tylenol). As this partial list indicates, oxidation of many classes of drugs can be inhibited in the presence of alcohol; these include HYPNOTICS, OPIOIDS, psychotropic drugs, anticonvulsants, vasodilators, antidiabetics, anticoagulants, ANALGESICS, and an-tibacterials. Chronic consumption of alcohol induces the P450 drug-metabolizing system, which could increase oxidation of drugs in sober or abstinent alcoholics. Among the drugs that may be more rapidly metabolized in abstinent alcoholics are eth-oxycoumarin, ethylmorphine, aminopyrine, anti-pyrine, pentobarbital, meprobamate, methadone, theophylline (Bronkodyl, Theo-Dur), tolbutamide, propranolol, rifamycin, warfarin, acetaminophen, phenytoin, deoxycline, and ethanol itself. An important consequence of this ability of chronic etha-nol intake to increase drug-clearance rates is that the effective therapeutic level of a drug will be different in an abstaining alcoholic than it is in a nondrinker. This metabolic drug tolerance can persist for several days to weeks after alcohol WITHDRAWAL.

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