Alcohol and Medication Interactions - a combination of alcohol and medication can impair driving and machinery operation abilities

Alcohol Research & Health, Wntr, 1999 by Ron Weathermon, David W. Crabb

In contrast to ADH, the alcohol-metabolizing enzyme cytochrome P450 - also called microsomal ethanol oxidizing system (MEOS) (Lieber 1994) - plays a central role in alcohol-medication interactions. Cytochrome P450 actually is a system consisting of two enzymes, one called cytochrome P450 reductase and another one called CYP2E1, which are both embedded in the membrane of a cell component called the endoplasmic reticulum.(3) In addition to alcohol, CYP2E 1 can metabolize numerous compounds, including acetaldehyde, the pain medication acetaminophen, the antibiotic isoniazid, and the barbiturate phenobarbital. Accordingly, CYP2E1 plays an important role in many alcohol-medication interactions.

In people consuming alcohol only occasionally, CYP2E1 metabolizes only a small fraction of the ingested alcohol. Chronic heavy drinking, however, can increase CYP2E1 activity up to tenfold, resulting in a substantial increase in the proportion of alcohol that is metabolized by this enzyme rather than by ADH [ILLUSTRATION FOR FIGURE 3 OMITTED] (Lieber 1994). The effect of lower levels of alcohol consumption on CYP2E1 activity is unknown. Because CYP2E1 also metabolizes several medications, alcoholics, in whom CYP2E1 activity is enhanced, exhibit increased metabolic rates for those medications when they are sober. When those alcoholics are intoxicated, however, the alcohol in their system competes with the medication for metabolism by CYP2E1. As a result, the breakdown of the medication is slowed. With many medications, increased or decreased metabolic rates can have adverse or even fatal consequences. With increased metabolic rates, the medication's concentration in the body may be too low or may decline too fast for it to be effective. Conversely, decreased metabolic rates may result in the accumulation of higher drug concentrations over longer periods of times, which may result in harmful overdoses.

Wide variation exists among people in both CYP2E1 activity and metabolic rates for medications broken down by this enzyme (e.g., acetaminophen and chlorzoxasone, a medication used to relieve muscle pain). Some of this variation may be genetically determined, although the specific underlying mechanism is unknown (Carriere et al. 1996). A person's CYP2E1 activity level, however, could influence his or her susceptibility to alcohol-medication interactions involving this enzyme. For example, in a person with innately low metabolic rates, a further decrease in metabolism when alcohol is consumed would affect medication levels (and thus the potential for adverse effects or interactions with alcohol) to a greater extent than in a person with innately high metabolic rates.

In addition to CYP2E1, at least two other cytochrome enzymes that metabolize various medications (i.e., CYP3A4 and CYP1A2) also can break down alcohol (Salmela et al. 1998). Moreover, the amounts of various enyzmes of the cytochrome CYP3A family (including CYP3A4) can increase from alcohol consumption (Niemela et al. 1998). Thus, potential interactions also exist between alcohol and medications metabolized by these cytochromes.