Cancer drugs – antimetabolites

Question 1

Methotrexate

Answer 1

Folic acid analog

Inhibits dihydrofolate reductase -> decreased thymidine, can’t replicate DNA synthesis

S phase specific

Cancer drug:
Leukemia (ALL, AML)
Lymphoma
Breast cancers
Sarcomas

Uterine pathology:
Choriocarcinomas
Hydatidiform mole
Ectomic pregnancy

Immunosuppression:
RA
Psoriasis

SE:
Myelosuppression reversible w/ leucovorin
-fibrotic lung dz
-teratogenicity – neural tube defect

Question 2

5-Flurouracil

Answer 2

S phase

Pyrimidine analog -> 5F-dUMP

• covalently binds to folic acid
• inhibits thymidylate synthase
• > dTMP and DNA synthesis inhibition

Use:
Colon cancer
Pancreatic cancer
Basal cell carcinoma
Actinic keratosis

SE:
Myelosuppression NOT reversible w/ leucovorin
-Uridine: rescue agent in OD

Photosensitivity w/ topical use

Question 3

6-Mercaptopurine

Answer 3

S phase

Purine analog

Inhibits glutamine PRPP amidotransferase
-> inhibited purine synthesis

metabolized by xanthine oxidase

• > increased toxicity w/ allopurinol or febuxostate
• > myelosuppression
• > hepatotoxicity

Question 4

6-thioguanine

Answer 4

Not metabolized by xanthine oxidase
Safe w/ allopurinol

Same as 6MP otherwise

Question 5

Cytarabine

Answer 5

Pyrimidine analog (C,T)
Inhibits DNA polymerase