Pharmacokinetics: drug metabolism in liver disease: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Pharmacokinetics: drug metabolism in liver disease

Sample item

A 55-year-old man with decompensated alcoholic cirrhosis needs a benzodiazepine for alcohol withdrawal. Which agent is preferred, and why?

AChlordiazepoxide, because its metabolites are inactiveBFlurazepam, because it has the shortest durationCLorazepam, because glucuronidation is relatively preserved and it has no active metabolitesDDiazepam, because it is cleared by oxidation even in liver failure

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Lorazepam, because glucuronidation is relatively preserved and it has no active metabolites

Lorazepam and oxazepam are cleared by phase II glucuronidation, which is relatively spared in cirrhosis, and they have no active metabolites. Diazepam and chlordiazepoxide undergo phase I oxidation to long-lived active metabolites that accumulate and risk precipitating hepatic encephalopathy.

Option by option

A. Chlordiazepoxide, because its metabolites are inactive
Chlordiazepoxide has long-acting active metabolites such as desmethyldiazepam.
B. Flurazepam, because it has the shortest duration
Flurazepam has a very long-acting active metabolite and is a hypnotic, not a short-acting agent.
C. Lorazepam, because glucuronidation is relatively preserved and it has no active metabolites (correct)
Correct. Conjugation with no active metabolites gives predictable effect in hepatic impairment.
D. Diazepam, because it is cleared by oxidation even in liver failure
Diazepam is cleared by oxidation, which is impaired in cirrhosis, and its metabolites accumulate.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is C, Lorazepam, because glucuronidation is relatively preserved and it has no active metabolites. Lorazepam and oxazepam are cleared by phase II glucuronidation, which is relatively spared in cirrhosis, and they have no active metabolites.

Why is "Chlordiazepoxide, because its metabolites are inactive" not the answer?

Chlordiazepoxide has long-acting active metabolites such as desmethyldiazepam.

Why is "Flurazepam, because it has the shortest duration" not the answer?

Flurazepam has a very long-acting active metabolite and is a hypnotic, not a short-acting agent.

Why is "Diazepam, because it is cleared by oxidation even in liver failure" not the answer?

Diazepam is cleared by oxidation, which is impaired in cirrhosis, and its metabolites accumulate.

What concept does this question test?

It tests Pharmacokinetics: drug metabolism in liver disease in Pharmacology. Diazepam and chlordiazepoxide undergo phase I oxidation to long-lived active metabolites that accumulate and risk precipitating hepatic encephalopathy.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Pharmacokinetics: drug metabolism in liver disease?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.