Purine catabolism: drug interaction: practice question

A Biochemistry 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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Biochemistry · Purine catabolism: drug interaction

Sample item

A man with gout is on allopurinol. Azathioprine is started at its usual dose after a renal transplant, and he develops pancytopenia within 3 weeks. What is the explanation?

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

The answer and the reasoning

B. Xanthine oxidase inhibition blocks inactivation of 6-mercaptopurine, so toxic levels build up

Azathioprine is converted to 6-mercaptopurine, which is inactivated mainly by xanthine oxidase to 6-thiouric acid. Allopurinol inhibits xanthine oxidase, so 6-MP accumulates and causes severe marrow suppression. The azathioprine dose must be reduced to about a quarter to a third if allopurinol is unavoidable.

Option by option

  • A. Allopurinol induces HGPRT, so more thioinosinic acid is formed

    Allopurinol does not induce HGPRT; the problem is reduced drug clearance.

  • B. Xanthine oxidase inhibition blocks inactivation of 6-mercaptopurine, so toxic levels build up (correct)

    Correct. Without xanthine oxidase the main inactivation route of 6-MP is lost.

  • C. Allopurinol blocks conversion of azathioprine to 6-mercaptopurine

    Azathioprine is converted to 6-MP non-enzymatically by glutathione, and allopurinol does not block this.

  • D. Azathioprine inhibits xanthine oxidase, causing hyperuricaemia

    Azathioprine does not inhibit xanthine oxidase; the interaction runs the other way.

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.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, Xanthine oxidase inhibition blocks inactivation of 6-mercaptopurine, so toxic levels build up. Azathioprine is converted to 6-mercaptopurine, which is inactivated mainly by xanthine oxidase to 6-thiouric acid.

Why is "Allopurinol induces HGPRT, so more thioinosinic acid is formed" not the answer?

Allopurinol does not induce HGPRT; the problem is reduced drug clearance.

Why is "Allopurinol blocks conversion of azathioprine to 6-mercaptopurine" not the answer?

Azathioprine is converted to 6-MP non-enzymatically by glutathione, and allopurinol does not block this.

Why is "Azathioprine inhibits xanthine oxidase, causing hyperuricaemia" not the answer?

Azathioprine does not inhibit xanthine oxidase; the interaction runs the other way.

What concept does this question test?

It tests Purine catabolism: drug interaction in Biochemistry. Allopurinol inhibits xanthine oxidase, so 6-MP accumulates and causes severe marrow suppression. The azathioprine dose must be reduced to about a quarter to a third if allopurinol is unavoidable.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. 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 Purine catabolism: drug interaction?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry 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.