Disulfiram increases the concentration of which benzodiazepine when used concomitantly?

Disulfiram increases the concentration of which benzodiazepine when used concomitantly?

• A. Diazepam
• B. Chlordiazepoxide
• C. Lorazepam
• D. Oxazepam

Answer: (B)

Disulfiram can slow liver enzymes that normally break down certain benzodiazepines, so those that depend on hepatic oxidation for their clearance are more likely to accumulate when used together. Chlordiazepoxide stands out here because it is a prodrug that is converted in the liver to desmethyldiazepam (nordiazepam), a long-acting active metabolite. If the hepatic metabolism is inhibited, the parent drug and its active metabolite build up, leading to higher concentrations and prolonged effects. By contrast, benzodiazepines such as lorazepam and oxazepam are mainly processed through glucuronidation (less dependent on these liver enzymes) and tend to be less affected by disulfiram. Diazepam is also metabolized by hepatic enzymes, but the classic interaction emphasized in this context is with chlordiazepoxide because of its prodrug nature and long-acting metabolites.

Disulfiram can slow liver enzymes that normally break down certain benzodiazepines, so those that depend on hepatic oxidation for their clearance are more likely to accumulate when used together. Chlordiazepoxide stands out here because it is a prodrug that is converted in the liver to desmethyldiazepam (nordiazepam), a long-acting active metabolite. If the hepatic metabolism is inhibited, the parent drug and its active metabolite build up, leading to higher concentrations and prolonged effects.

By contrast, benzodiazepines such as lorazepam and oxazepam are mainly processed through glucuronidation (less dependent on these liver enzymes) and tend to be less affected by disulfiram. Diazepam is also metabolized by hepatic enzymes, but the classic interaction emphasized in this context is with chlordiazepoxide because of its prodrug nature and long-acting metabolites.