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alkylators MOA
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.
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alkylators kinetics
cyclophosphamide PO, bendamustine IV. nitrosureas lipophilic so good CNS penetration.
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alkylators contraindications
cyclophosphamide leukopenia, thrombocytopenia.
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alkylators SE
toxicities (pulmonary, kidney, bladder), hemorrhagic cystitis, leukemia.
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anthracyclines MOA
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.
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anthracyclines kinetics
doxorubicin is a prodrug, converted to idarubicin. doxorubicin sequested in liposomes (avoids cardiotoxicity).
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anthracyclines contraindications
severe cardiac disease
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anthracyclines interactions
anthracyclines + trastuzumab = bad for heart
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anthracyclines SE
cardiotoxicity, mucositis/stomatitis, soft tissue necrosis.
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antimetabolites MOA
folate antagonists inhibit DHFR, which is required for purine synthesis.
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antimetabolites MOA
interfere with one or more enzymes or reactions needed for DNA synthesis
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antimetabolites kinetics
methotrexate doesn't cross the BBB, so interthecal administration if needed there
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antimetabolites interactions
folate analogues + other drugs secreted in the proximal tubule (ie. aspirin) = reduced clearance
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antimetabolites SE
GI (epithelial damage, stomatitis), pneumonitis, nephro/hepatotoxicity, dermatitis, defective oogenesis/spermatogenesis. mercaptopurine hepatotoxicity. fludarabine altered mental status, seizures.
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bleomycin MOA
intercalates into DNA
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bleomycin SE
cutaneous (hyperpigmentation, hyperkeratosis, erythema, ulceration). interstitial pneumonitis/fibrosis.
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bleomycin bonus
unlike most agents, bleomycin causes minimal bone marrow suppression so it is often included in many regimens.
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platinum compounds MOA
the platinum ions cross-link DNA strands, inhibiting synthesis/function. if damaged enough, cell will undergo apoptosis.
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platinum compounds SE
tinnitus, hearing loss, peripheral neuropathy. nephrotoxicity (especially cisplatin).
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platinum compounds bonus
myelosuppression less severe with platinum compounds than with other conventional drugs. pre/post infusion with calcium and magnesium used to help prevent neuropathy.
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taxanes MOA
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.
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taxanes indications
prevention of restenosis after angioplasty
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taxanes contraindications
severe hepatic impairment
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taxanes SE
neurotoxicity, resistant fluid retention (pretreat c dexamethasone), (hypersensitivity to solvent, not drug)
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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).
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topoisomerase inhibitors kinetics
IV. etoposide also PO.
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topoisomerase inhibitors contraindications
topotecan severe bone marrow suppression, severe renal impairment. ironotecan concomitant use with potent CYP3A4 inhibitors (ketoconazole).
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topoisomerase inhibitors SE
interstitial lung disease. ironotecan severe diarrhea (tx early onset = atropine, severe late onset = loperamide). etoposide hypersensitivity, transient hypotension.
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topoisomerase inhibitors bonus
pts with UGT1A1*28 polymorphism will have reduced metabolism of irinotecan (10% of the population).
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vinca alkaloids MOA
microtubule inhibitors (inhibits b-tubulin polymerization), preventing chromosomes from aligning normally.
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vinca alkaloids kinetics
IV but long T1/2 (1-2 days)
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vinca alkaloids contraindications
neurologic diseases, intrathecal administration, severe bone marrow suppression.
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vinca alkaloids SE
peripheral neuropathy. vinblastine has least neurotoxicity.
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vinca alkaloids bonus
vincristine least likely to suppress bone marrow, so more likely in hematologic cancer regimens.
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GnRH analogues kinetics
goserelin/leuprolide both long-acting (1+ month) injections. buserelin can be a nasal spray.
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GnRH analogues contraindications
undiagnosed vaginal bleeding
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GnRH SE
related to either androgen deprivation or estrogen deprivation. agonists ovarian hyperstimulation syndrome. antagonists allergic reactions.
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angiogenesis inhibitors MOA
bind to VEGF-A, preventing it from binding to its receptors and promoting angiogenesis.
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angiogenesis inhibitors SE
GI perforation, hemorrhage, HTN, thrombosis, decreased wound healing.
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tyrosine kinase inhibitor targets
HER2, EGFR, BCR-ABL, multiple
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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)
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tyrosine kinase inhibitor kinetics.
all PO, reduced absorption c high fat meals.
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tyrosine kinase inhibitor SE
left ventricular dysfunction, fluid retention, QT prolongation, hemorrhage, interstitial lung disease, toxicities (heart, lungs, liver).
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