Page 484 - First Aid for the USMLE Step 1 2020, Thirtieth edition [MedicalBooksVN.com]_Neat
P. 484
440 SectIon III Hematology and oncology ` hematology and oncology—PhaRmacology Hematology and oncology ` hematology and oncology—PhaRmacology
Antimetabolites
dRUg mechanISm a clInIcal USe adVeRSe eFFectS
Azathioprine, Purine (thiol) analogs Preventing organ rejection, Myelosuppression; GI, liver
6-mercaptopurine de novo purine synthesis. rheumatoid arthritis, IBD, toxicity.
Activated by HGPRT. SLE; used to wean patients Azathioprine and 6-MP are
Azathioprine is metabolized off steroids in chronic disease metabolized by xanthine
into 6-MP. and to treat steroid-refractory oxidase; thus both have risk
chronic disease. of toxicity with allopurinol or
febuxostat.
Cladribine Purine analog multiple Hairy cell leukemia. Myelosuppression,
mechanisms (eg, inhibition nephrotoxicity, and
of DNA polymerase, DNA neurotoxicity.
strand breaks).
Cytarabine Pyrimidine analog DNA Leukemias (AML), lymphomas. Myelosuppression with
(arabinofuranosyl chain termination. At higher megaloblastic anemia.
cytidine) concentrations, inhibits DNA CYTarabine causes
polymerase. panCYTopenia.
5-fluorouracil Pyrimidine analog bioactivated Colon cancer, pancreatic Myelosuppression, palmar-
to 5-FdUMP, which cancer, actinic keratosis, basal plantar erythrodysesthesia
covalently complexes with cell carcinoma (topical). (hand-foot syndrome).
thymidylate synthase and Effects enhanced with the
folic acid. Capecitabine is a addition of leucovorin.
prodrug.
This complex inhibits
thymidylate synthase
dTMP DNA
synthesis.
Methotrexate Folic acid analog that Cancers: leukemias Myelosuppression, which is
competitively inhibits (ALL), lymphomas, reversible with leucovorin
dihydrofolate reductase choriocarcinoma, sarcomas. (folinic acid) “rescue.”
dTMP DNA Non-neoplastic: ectopic Hepatotoxicity.
synthesis. pregnancy, medical Mucositis (eg, mouth ulcers).
abortion (with misoprostol), Pulmonary fibrosis.
rheumatoid arthritis, psoriasis, Folate deficiency, which
IBD, vasculitis. may be teratogenic (neural
tube defects) without
supplementation.
Nephrotoxicity.
a All are S-phase specific except cladribine, which is cell cycle nonspecific.
FAS1_2019_10-HemaOncol.indd 440 11/7/19 5:05 PM
