Antimetabolites

• methotrexate

  • mechanism: inhibits dihydrofolate reductase (DHFR), so you can’t make purines

  • if overdose occurs, rescue with leucovorin, a tetrahydrofolate

  • resistance: impaired transport, gene amplification or mutation of DHFR

  • toxicities: pulmonary (pneumonitis—looks like pneumonia; rx with steroids), hepatic (cirrhosis)

  • teratogenic

• Ara-C (cytosine arabinoside)

  • used for all leukemia patients

  • mechanism: incorporated into DNA

  • toxicity: liver and CNS (clinically, check for nystagmus)

• 5’FU (5’fluorouracil) IV; capecitabine (prodrug) PO

  • if you add leucovorin, this drug becomes more effective

  • toxicities: diarrhea, skin toxicity (hands and feet turn red, swollen, and painful)

• fludarabine

  • mechanism: adenosine analog

  • toxicities: depletes T cells, leading to opportunistic infections

Category: Pharmacology Notes