Paper II — 2015 September (Supplementary) (2010 Scheme) — Q10

Paper II

2015 September (Supplementary) (2010 Scheme) · 40 marks · 120 min

Question

Rationale for the use of folinic acid in methotrexate toxicity.

Q101 marksShort Answers★✓

Answer

Methotrexate inhibits dihydrofolate reductase, blocking regeneration of tetrahydrofolate (the active folate cofactor needed for nucleotide/DNA synthesis) — this affects both malignant and normal rapidly dividing cells, causing toxicity (myelosuppression, mucositis). Folinic acid (leucovorin, a reduced folate) bypasses the blocked enzymatic step by directly providing the active tetrahydrofolate derivative, “rescuing” normal cells from methotrexate toxicity without significantly rescuing tumour cells (which typically take up folinic acid less efficiently) — this is the basis of “leucovorin rescue” used with high-dose methotrexate therapy.

Related Concepts

1. 1Cancer Chemotherapy

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