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Paper II — 2025 August (Supplementary) (2010 Scheme) — Q6

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Paper II
2025 August (Supplementary) (2010 Scheme)

Question

Methotrexate

Q63 marksShort Notes

Answer

Methotrexate is a folate-antagonist antimetabolite, cell-cycle-specific (S-phase).

MOA: methotrexate → competitively inhibits dihydrofolate reductase → blocks tetrahydrofolate regeneration → halts purine and thymidine synthesis → arrests DNA replication. Leucovorin (folinic acid) rescue allows higher, more effective doses while rescuing normal host cells from lethal antifolate toxicity.

Uses: acute lymphoblastic leukemia, lymphomas, choriocarcinoma; at much lower, non-oncologic doses — rheumatoid arthritis and psoriasis.

Adverse effects: bone marrow suppression, mucositis, hepatotoxicity, nephrotoxicity, teratogenicity, pulmonary fibrosis with chronic low-dose use.

  1. 1Cancer Chemotherapy

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