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Pharmacology · single question

What is the mechanism of action of methotrexate?

  1. It inhibits dihydrofolate reductase, blocking DNA and RNA synthesis
  2. It inhibits HMG-CoA reductase
  3. It blocks tumor necrosis factor alpha
  4. It irreversibly inhibits cyclooxygenase
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Correct answer: A. It inhibits dihydrofolate reductase, blocking DNA and RNA synthesis

  • A. CORRECT. Methotrexate is a FOLATE ANALOG that competitively inhibits DIHYDROFOLATE REDUCTASE, depleting tetrahydrofolate. This blocks synthesis of purines and thymidylate, halting DNA and RNA synthesis in rapidly dividing cells. That is why it produces myelosuppression, oral mucositis and ulceration, and hepatotoxicity. Folic acid supplementation reduces these effects; leucovorin is the rescue agent in overdose. NSAIDs raise methotrexate levels and should be avoided.
  • B. HMG-CoA reductase inhibition is the statin mechanism.
  • C. TNF-alpha blockade is the mechanism of adalimumab, etanercept, and infliximab.
  • D. Irreversible COX inhibition is aspirin's mechanism.

Note: Practical dental point: AVOID prescribing NSAIDs to a patient on methotrexate — they reduce renal clearance and can precipitate toxicity.

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