trasfer alkyl (chemical) groups to DNA, leading to strand breakage and the death of the cell. nitrosoureas (ie. bendamustine) also carbamoylate proteins, limiting the ability of cells to repair their DNA.
cyclophosphamide PO, bendamustine IV. nitrosureas lipophilic so good CNS penetration.
prevent the resealing of DNA by topoisomerase II, resulting in a large number of DNA fragments that eventually prompt apoptosis. also produce free radicals, damaging membranes/proteins/lipids. also intercalate, inhibiting transcription/replication.
doxorubicin is a prodrug, converted to idarubicin. doxorubicin sequested in liposomes (avoids cardiotoxicity).
myelosuppression less severe with platinum compounds than with other conventional drugs. pre/post infusion with calcium and magnesium used to help prevent neuropathy.
microtubule inhibitors (specifically, binds to b-tubulin, stabilizing it so it can't dissolve like it is supposed to). tubules are key to chromosome segregation during mitosis.
prevention of restenosis after angioplasty
severe hepatic impairment
neurotoxicity, resistant fluid retention (pretreat c dexamethasone), (hypersensitivity to solvent, not drug)
topoisomerase inhibitors MOA
camptothecins inhibit topoisomerase I (single stranded DNA), while polophyllotoxins inhibit topoisomerase II (double stranded DNA), blocking the resealing of breaks in the DNA (fragmented DNA leads to cell death).
topoisomerase inhibitors kinetics
IV. etoposide also PO.
topoisomerase inhibitors contraindications
topotecan severe bone marrow suppression, severe renal impairment. ironotecan concomitant use with potent CYP3A4 inhibitors (ketoconazole).
topoisomerase inhibitors SE
interstitial lung disease. ironotecan severe diarrhea (tx early onset = atropine, severe late onset = loperamide). etoposide hypersensitivity, transient hypotension.
topoisomerase inhibitors bonus
pts with UGT1A1*28 polymorphism will have reduced metabolism of irinotecan (10% of the population).
vinca alkaloids MOA
microtubule inhibitors (inhibits b-tubulin polymerization), preventing chromosomes from aligning normally.
vinca alkaloids kinetics
IV but long T1/2 (1-2 days)
vinca alkaloids contraindications
neurologic diseases, intrathecal administration, severe bone marrow suppression.
vinca alkaloids SE
peripheral neuropathy. vinblastine has least neurotoxicity.
vinca alkaloids bonus
vincristine least likely to suppress bone marrow, so more likely in hematologic cancer regimens.
GnRH analogues kinetics
goserelin/leuprolide both long-acting (1+ month) injections. buserelin can be a nasal spray.
GnRH analogues contraindications
undiagnosed vaginal bleeding
related to either androgen deprivation or estrogen deprivation. agonists ovarian hyperstimulation syndrome. antagonists allergic reactions.
angiogenesis inhibitors MOA
bind to VEGF-A, preventing it from binding to its receptors and promoting angiogenesis.
angiogenesis inhibitors SE
GI perforation, hemorrhage, HTN, thrombosis, decreased wound healing.
tyrosine kinase inhibitor targets
HER2, EGFR, BCR-ABL, multiple
tyrosine kinase inhibitor MOA
bind to growth receptors (tyrosine kinases) that regulate cell division, prevents them from signaling to divide (often permanently "on" in cancers)