pharm - oncology.txt

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.

cyclophosphamide leukopenia, thrombocytopenia.

toxicities (pulmonary, kidney, bladder), hemorrhagic cystitis, leukemia.

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).

severe cardiac disease

anthracyclines + trastuzumab = bad for heart

cardiotoxicity, mucositis/stomatitis, soft tissue necrosis.

folate antagonists inhibit DHFR, which is required for purine synthesis.

interfere with one or more enzymes or reactions needed for DNA synthesis

methotrexate doesn't cross the BBB, so interthecal administration if needed there

folate analogues + other drugs secreted in the proximal tubule (ie. aspirin) = reduced clearance

GI (epithelial damage, stomatitis), pneumonitis, nephro/hepatotoxicity, dermatitis, defective oogenesis/spermatogenesis. mercaptopurine hepatotoxicity. fludarabine altered mental status, seizures.

intercalates into DNA

cutaneous (hyperpigmentation, hyperkeratosis, erythema, ulceration). interstitial pneumonitis/fibrosis.

unlike most agents, bleomycin causes minimal bone marrow suppression so it is often included in many regimens.

the platinum ions cross-link DNA strands, inhibiting synthesis/function. if damaged enough, cell will undergo apoptosis.

tinnitus, hearing loss, peripheral neuropathy. nephrotoxicity (especially cisplatin).

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)

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).

IV. etoposide also PO.

topotecan severe bone marrow suppression, severe renal impairment. ironotecan concomitant use with potent CYP3A4 inhibitors (ketoconazole).

interstitial lung disease. ironotecan severe diarrhea (tx early onset = atropine, severe late onset = loperamide). etoposide hypersensitivity, transient hypotension.

pts with UGT1A1*28 polymorphism will have reduced metabolism of irinotecan (10% of the population).

microtubule inhibitors (inhibits b-tubulin polymerization), preventing chromosomes from aligning normally.

IV but long T1/2 (1-2 days)

neurologic diseases, intrathecal administration, severe bone marrow suppression.

peripheral neuropathy. vinblastine has least neurotoxicity.

vincristine least likely to suppress bone marrow, so more likely in hematologic cancer regimens.

goserelin/leuprolide both long-acting (1+ month) injections. buserelin can be a nasal spray.

undiagnosed vaginal bleeding

related to either androgen deprivation or estrogen deprivation. agonists ovarian hyperstimulation syndrome. antagonists allergic reactions.

bind to VEGF-A, preventing it from binding to its receptors and promoting angiogenesis.

GI perforation, hemorrhage, HTN, thrombosis, decreased wound healing.

HER2, EGFR, BCR-ABL, multiple

bind to growth receptors (tyrosine kinases) that regulate cell division, prevents them from signaling to divide (often permanently "on" in cancers)

all PO, reduced absorption c high fat meals.

left ventricular dysfunction, fluid retention, QT prolongation, hemorrhage, interstitial lung disease, toxicities (heart, lungs, liver).