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Benzodiazepines in Liver Disease — MRCPsych Paper B MCQ

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HardSubstance MisuseBenzodiazepines in Liver DiseaseMRCPsych Paper B

A 55-year-old man with alcohol dependence has stable compensated alcohol-related cirrhosis without hepatic encephalopathy. Following specialist assessment, a benzodiazepine is considered essential for no more than 7 days to treat disabling anxiety. Which benzodiazepine has the most favourable pharmacokinetic profile for minimising accumulation caused by impaired hepatic metabolism?

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Correct answer: AOxazepam

A. Oxazepam has the most favourable pharmacokinetic profile among the listed drugs. It is converted directly by glucuronidation to a pharmacologically inactive metabolite, so it is less liable to accumulation from impaired phase I oxidative metabolism. Diazepam and chlordiazepoxide undergo hepatic oxidation and produce long-lived active metabolites, increasing the risk of prolonged sedation. Midazolam is short acting after a single dose but depends substantially on CYP3A metabolism, which may be impaired in cirrhosis. Nitrazepam is relatively long acting and offers no comparable metabolic advantage. This is a relative preference, not evidence that oxazepam is generally safe: use the lowest effective dose for the shortest duration, exercise extreme caution because of alcohol dependence, and avoid all benzodiazepines in severe hepatic insufficiency because they may precipitate encephalopathy.

Reference: electronic Medicines Compendium, Oxazepam 10 mg Tablets, Summary of Product Characteristics, sections 4.2–4.4 and 5.2, revised 23 December 2025. https://www.medicines.org.uk/emc/product/11747/smpc