Chemotherapy: leucovorin with fluorouracil: 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: leucovorin with fluorouracil

Sample item

Leucovorin is given together with fluorouracil in the FOLFOX regimen for colorectal cancer. How does leucovorin increase the activity of fluorouracil?

AIt inhibits dihydropyrimidine dehydrogenase and slows drug breakdownBIt supplies reduced folate that stabilises the FdUMP-thymidylate synthase complexCIt raises tumour uptake of the drug through P-glycoproteinDIt bypasses dihydrofolate reductase to rescue normal marrow cells

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

The answer and the reasoning

B. It supplies reduced folate that stabilises the FdUMP-thymidylate synthase complex

Fluorouracil is converted to FdUMP, which binds thymidylate synthase. A reduced folate cofactor stabilises this ternary complex and prolongs enzyme inhibition. This potentiation differs from the rescue role of leucovorin after methotrexate.

Option by option

A. It inhibits dihydropyrimidine dehydrogenase and slows drug breakdown
Inhibiting dihydropyrimidine dehydrogenase is the purpose of agents such as eniluracil, not leucovorin.
B. It supplies reduced folate that stabilises the FdUMP-thymidylate synthase complex (correct)
Correct. The reduced folate keeps FdUMP locked onto thymidylate synthase.
C. It raises tumour uptake of the drug through P-glycoprotein
P-glycoprotein effluxes drugs from cells, and leucovorin does not increase fluorouracil uptake through it.
D. It bypasses dihydrofolate reductase to rescue normal marrow cells
Bypassing the dihydrofolate reductase block describes methotrexate rescue, which is not the aim here.

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 B, It supplies reduced folate that stabilises the FdUMP-thymidylate synthase complex. Fluorouracil is converted to FdUMP, which binds thymidylate synthase.

Why is "It inhibits dihydropyrimidine dehydrogenase and slows drug breakdown" not the answer?

Inhibiting dihydropyrimidine dehydrogenase is the purpose of agents such as eniluracil, not leucovorin.

Why is "It raises tumour uptake of the drug through P-glycoprotein" not the answer?

P-glycoprotein effluxes drugs from cells, and leucovorin does not increase fluorouracil uptake through it.

Why is "It bypasses dihydrofolate reductase to rescue normal marrow cells" not the answer?

Bypassing the dihydrofolate reductase block describes methotrexate rescue, which is not the aim here.

What concept does this question test?

It tests Chemotherapy: leucovorin with fluorouracil in Pharmacology. A reduced folate cofactor stabilises this ternary complex and prolongs enzyme inhibition. This potentiation differs from the rescue role of leucovorin after methotrexate.

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 Chemotherapy: leucovorin with fluorouracil?

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.