Alcohol and Drug Interactions

Fatal toxicity may occur from alcohol and drug overdoses. In many instances, in the presence of alcohol, a lower concentration of drug may cause fatality because of drug-alcohol interactions. In a Finnish study, it was found that median amitriptyline and propoxyphene concentrations were lower in alcohol-related fatal cases compared with cases where no alcohol was involved. The authors concluded that when alcohol is present, a relatively small overdose of a drug may cause fatality (56). Although alcohol is mostly metabolized in the liver by hepatic alcohol dehydrogenase, long-term intake of large amount of alcohol induces other pathways of metabolism, in particular, the microsomal alcohol-oxidizing system involving CYP2E1. In contrast, acute ingestion of alcohol is likely to cause inhibition of this enzyme (57). CYP2E1 also metabolizes and activates many toxicological substrates to more active products, and induction of CYP2E1 plays an important role in oxidative stress and toxicity in ethanol-induced liver injury (58).

There are two types of interactions between alcohol and a drug: pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions occur when alcohol interferes with the hepatic metabolism of a drug. Pharmacodynamic interactions occur when alcohol enhances the effect of a drug, particularly in the central nervous system. In this type of interaction, alcohol alters the effect of a drug without changing its concentration in the blood (59). The package insert of many antibiotics states that the medication should not be taken with alcohol although only a few antibiotics have reported interactions with alcohol. Erythromycin may increase blood concentration of alcohol by accelerating gastric emptying (59). Histamine H2 receptor antagonists, such as cimetidine, ranitidine, nizatidine, and famotidine, reduce the activity of alcohol dehydrogenase (60). DiPadova et al. studied the interactions between alcohol and cimetidine, ranitidine as well as famotidine using human subjects. Relative to baseline, ranitidine increased the mean peak concentration and area under the curve (AUC) of blood alcohol by 34 and 41%, respectively. First-pass metabolism of ethanol was also decreased significantly with an increase in bioavailability from 79.6 to 92.6%. Cimetidine showed a greater effect on blood alcohol levels compared with ranitidine, but famotidine showed no significant effect. The authors concluded that patients taking cimetidine or ranitidine should be warned of possible impairments after consumption of alcohol in quantities usually considered as safe in the absence of therapy with these medications (61). However, another study contradicted these findings and concluded that under real life conditions, the concomitant administration of alcohol and cimetidine, ranitidine, or omeprazole is unlikely to have significant physical, social, or forensic implications because no significant difference was found between percentage of first-pass metabolism, peak blood alcohol concentration, or AUC following administration of cimetidine, ranitidine, or omeprazole (62). Another report also found no significant interaction between alcohol and lansoprazole or omeprazole (63).

The effect of alcohol, even low-dose alcohol, on the enhanced antithrombotic effect of warfarin is of clinical significance. A 58-year-old Caucasian man was receiving long-term anticoagulation therapy with warfarin and had a stable International Normalization Ratio (INR). His INR increased when he started taking low-dose beer for cardiovascular protection. After he stopped the alcohol, his INR returned to normal (64). This excessive warfarin activity from low alcohol consumption may be related to the inhibition of warfarin metabolism by cytochrome P450. Conversely, in people who chronically drink alcohol, long-term alcohol consumption activates cytochrome P450 and may increase warfarin metabolism (59).

Alcohol increases sedative effect of tricyclic antidepressants (TCAs) through pharmacodynamic interactions. In addition, alcohol can also cause pharmacokinetic interactions. Alcohol appears to interfere with first-pass metabolism of amitriptyline, thus increasing serum levels of this drug. Alcohol has pharmacodynamic effects with antihistamines, increasing the sedative effects of these over the counter and prescription drugs. Alcohol also increases the sedative effect of phenobarbital and may also increase its serum concentration through pharmacokinetic interactions. Interactions between benzodiazepines and alcohol have also been reported. Alcohol consumption may result in accumulation of toxic breakdown products of acetaminophen (59).

Alcohol No More

Alcohol No More

Do you love a drink from time to time? A lot of us do, often when socializing with acquaintances and loved ones. Drinking may be beneficial or harmful, depending upon your age and health status, and, naturally, how much you drink.

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