Reply To: NEET SS Clinical Hematology 2020 Telegram Group Discussion MCQs

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Answer 57 = [3]
Answer 58 = [3]
Methotrexate
Cell cycle–specific antifolate analog, active in S-phase of the cell cycle.

Mechanism:- Antifolate
Inhibition of dihydrofolate reductase (DHFR) resulting in depletion of critical reduced folates.
Inhibition of de novo thymidylate synthesis.
Inhibition of de novo purine synthesis.
Incorporation of dUTP into DNA resulting in inhibition of DNA synthesis and function.

Toxicity:-
Myelosuppression is dose-limiting toxicity
Mucositis can also be dose-limiting toxicity.
Renal toxicity results from the intratubular precipitation of methotrexate and its metabolites.
Poorly defined pneumonitis characterized by fever, cough, and interstitial pulmonary infiltrates.

Preventing toxicity:-
[1] Hydration = With high-dose therapy it is important to vigorously hydrate the patient with with NS and Sodium bicarbonate should be included in the IV fluid to ensure that the urine pH is greater than 7.0 at the time of drug infusion and ideally for up to 48–72 hours after drug is given.
[2] Rescue with leucovorin or L-leucovorin, the active isomer of leucovorin, should begin at 24 hours after drug infusion.
[3] Glucarpidase (Antidote) is indicated for the treatment of toxic plasma methotrexate concentrations in patients with delayed drug clearance due to impaired renal function.