Chemotherapy: fluorouracil and DPD deficiency: 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 · Chemotherapy: fluorouracil and DPD deficiency

Sample item

A 60-year-old woman with colon cancer develops severe mucositis, diarrhoea and neutropenia within days of her first fluorouracil infusion. Which enzyme deficiency is most likely?

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

The answer and the reasoning

D. Dihydropyrimidine dehydrogenase

Dihydropyrimidine dehydrogenase degrades more than 80% of an administered dose of fluorouracil, and deficiency (DPYD variants) leads to severe, sometimes fatal toxicity. Capecitabine, a prodrug of fluorouracil, shares the risk. Testing for DPYD variants before treatment is recommended in many centres.

Option by option

  • A. UDP-glucuronosyltransferase 1A1

    UGT1A1 variants cause severe irinotecan toxicity.

  • B. Thiopurine methyltransferase

    TPMT deficiency causes toxicity with mercaptopurine and azathioprine.

  • C. CYP2D6

    CYP2D6 variants alter activation of tamoxifen and codeine.

  • D. Dihydropyrimidine dehydrogenase (correct)

    Correct. Reduced catabolism raises fluorouracil exposure and toxicity.

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 Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Dihydropyrimidine dehydrogenase. Dihydropyrimidine dehydrogenase degrades more than 80% of an administered dose of fluorouracil, and deficiency (DPYD variants) leads to severe, sometimes fatal toxicity.

Why is "UDP-glucuronosyltransferase 1A1" not the answer?

UGT1A1 variants cause severe irinotecan toxicity.

Why is "Thiopurine methyltransferase" not the answer?

TPMT deficiency causes toxicity with mercaptopurine and azathioprine.

Why is "CYP2D6" not the answer?

CYP2D6 variants alter activation of tamoxifen and codeine.

What concept does this question test?

It tests Chemotherapy: fluorouracil and DPD deficiency in Pharmacology. Capecitabine, a prodrug of fluorouracil, shares the risk. Testing for DPYD variants before treatment is recommended in many centres.

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 Chemotherapy: fluorouracil and DPD deficiency?

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.