Which liver enzyme system is commonly induced by chronic alcohol use, affecting drug metabolism?

• A. UDP-glucuronosyltransferase
• B. Cytochrome P450 system, particularly CYP2E1
• C. Monoamine oxidase
• D. Glutathione S-transferase

Answer: (B)

Chronic alcohol use ramps up certain liver enzymes to handle the constant influx of ethanol, and the most clinically relevant system it induces for drug metabolism is the cytochrome P450 family, especially CYP2E1. When CYP2E1 levels rise, many drugs that are substrates of this enzyme are broken down more quickly. That faster metabolism can lower a drug’s blood levels, potentially reducing effectiveness or requiring dose adjustments. It also raises the risk of drug interactions, because other substances that induce or compete for this pathway can further alter how quickly drugs are cleared. An important related point is that CYP2E1 activity can increase formation of a toxic metabolite from acetaminophen, particularly if glutathione stores are depleted, contributing to liver injury risk with alcohol use.

The other enzymes listed don’t show the same well-established pattern of chronic alcohol–induced upregulation that broadly changes drug metabolism. Therefore, the cytochrome P450 system, especially CYP2E1, best explains how chronic alcohol use affects drug metabolism.