Antimetabolites

Question 1

Methotrexate (MTX)

Answer 1

Folic acid analog that inhibits dihydrofolate reductase –> decrease dTMP –> decrease DNA and decrease protein synthesis;

Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas
Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis

Toxicity: Myelosuppression (use leucovorin)
macrovesicular fatty change in liver
mucositis
teratogenic

Question 2

5-fluoruracil (5-FU)

Answer 2

Pryimidine analog; covalently complexes to folic acid;
inhibits thymidylate synthase –> decrease dTMP –> decrease DNA and protein synthesis

Use: colon cancer, solid tumors, basal cell carcinoma (topical); synergy with MTX
toxicity: myelosuppresion, overdose rescue with thymidine; photosensitivity

Question 3

6-mercaptopurine (6-MP)

Answer 3

purine (thiol) analog –> decreases de novo purine synthesis; activated by HGPRTase

use: leukemias, lymphomas (not CLL or Hodgkin’s)
toxicity: Bone marrow, GI, liver, metabolized by xanthine oxidase (allopurinol increases toxicity)

Question 4

6-thioguanine (6-TG)

Answer 4

same as 6-MP
Use: ALL
toxicity: bone marrow depression, liver. Can be given with allopurinol.

Question 5

Cytarabine (ara-C)

Answer 5

pyrimidine analog –> inhibition of DNA polymerase

use: AML, ALL, high-grade NHL
toxicity: leukopenia, thrombocytopenia, megaloblastic anemia