Heme/Onc Drugs Flashcards
Cyclophosphamide mechanism
Crosslink DNA at guanine N-7 (inhibits DNA replication)
What drug causes ototoxicity?
Cisplatin/Carboplatin
What drug causes peripheral neuropathy?
Vincristine
What drugs cause cardiotoxicity? What can you give to prevent this?
1) Doxorubicin (dilated cardiomyopathy) – give Dexrazoxane to prevent this
2) Trastuzumab
What drugs cause pulmonary fibrosis?
Bleomycin, Busulfan
Methotrexate
What drugs are nephrotoxic? What can you give to prevent this?
Cisplatin/Carboplatin
Prevent with Amifostine and saline (Cl-) diuresis
What drug causes hemorrhagic cystitis? What can you give to prevent this?
Cyclophosphamide
Give Mesna to prevent this
What drugs cause myelosuppression?
5-FU
6-MP
Methotrexate
Vincristine/Vinblastine
vinca alkaloids that are microtubule inhibitors (M phase)
Can cause peripheral neuropathy and constipation
6-Mercaptopurine mechanism of action
purine analog that decrease purine synthesis –> dec DNA synthesis (S phase)
What metabolizes 6-Mercaptopurine
Metabolized by xanthine oxidase – thus have increased toxicity when taken with allopurinol or Febuxostat (because less xanthine oxidase is available to metabolize 6-MP)
Etoposide/Teniposide
inhibits topoisomerase II → inc DNA degradation
o “Etoposide inhibits topoisomerase two”
Irinotecan/topotecan:
inhibit topoisomerase I and prevent DNA unwinding and replication
Methotrexate mechanism of action and side effects
folic acid analog that inhibits dihydrofolate reductase (DHF reductase) and decreases DNA synthesis
o Causes myelosuppression – reversible with Leucovorin
o Causes pulmonary fibrosis
Leucovorin in 5-Fluorouracil and Methotrexate induced myelosuppression
Leucovorin reverses Methotrexate induced myelosuppression but worsens it in 5-FU
5-fluorouracil
complexes to folic acid and inhibits thymidylate synthase, causing dec DNA synthesis (S phase)
o Effects are enhanced with addition of Leucovorin (folinic acid)
o Myelosuppression is worsened with administration of Leucovorin
Doxorubicin
generates free radicals that cause breaks in DNA (G2 phase)
Causes cardiotoxicity – dilated cardiomyopathy (which can be prevented with Dexrazoxane)
Methotrexate mechanism of action and side effects
folic acid analog that inhibits dihydrofolate reductase (DHF reductase) and decreases DNA synthesis
o Causes myelosuppression – reversible with Leucovorin
o Causes pulmonary fibrosis
Busulfan
cross links DNA
o Causes Myelosuppression, pulmonary fibrosis, and hyperpigmentation
Bleomycin
generates free radicals that create breaks in DNA (G2 phase)
o Causes pulmonary fibrosis and hyperpigmentation
Tamoxifen/Raloxifene mechanism and risks
selective estrogen receptor modulators (SERMs) that block the binding of estrogen in estrogen sensitive breast cancers
o Estrogen receptor antagonists in breast and agonists in bone (can promote bone strength)
o Tamoxifen is a partial agonist in endometrial tissue, which inc the risk of endometrial cancer
o Inc in DVT/PE risk
Trastuzumab (Herceptin)
Monoclonal Ab against HER-2 a tyrosine kinase receptor
o Helps kill cancer cells that overexpress HER-2
o Useful against HER-2 + breast cancer
o Can cause cardiotoxicity
What drugs are microtubule inhibitors and act on the M phase of the cell cycle? How do their mechanisms differ?
Paclitaxel: hyperstabilizes the microtubules in M phase and prevents breakdown of the mitotic spindle
Vincristine/vinblastine: vinca alkaloids that block polymerization of microtubules and prevent microtubule formation (M phase)
