Paper II
2017 February (2010 Scheme) · 40 marks · 120 min

Question

Methotrexate.

Q63 marksShort Notes

Answer

Methotrexate is a folate antagonist (antimetabolite).

Mechanism of action

  • Inhibits dihydrofolate reductase, blocking regeneration of tetrahydrofolate needed for purine/thymidylate synthesis — impairs DNA synthesis (S-phase specific)

Uses

  • Malignancies: acute lymphoblastic leukaemia, choriocarcinoma, osteosarcoma
  • Rheumatoid arthritis (low-dose, weekly — first-line DMARD)
  • Psoriasis
  • Ectopic pregnancy

Adverse effects

  • Myelosuppression
  • Mucositis
  • Hepatotoxicity, nephrotoxicity
  • Teratogenic
  • Pulmonary fibrosis (chronic use)

Rescue agent: Folinic acid (leucovorin)

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