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s-phase specific. inhibits DNA polymerase causing chain termination and inhibits ribonucleotide reductase
s-phase specific. incorporates metabolites into DNA causing miscoding during DNA replication. inhibits de novo purine synthesis
s-phase specific, inhibits DNA polymerase, inhibits replication of DNA and causes chain termination
dose dependent: cerebellar toxicity, conjunctivitis, myelosuppression
other- mucositis, N/V, rash, "ara-C syndrome"
s-phase specific. inhibits dna polymerase and ribonucleotide reductase. terminates chain elongation
depends on +/- leucovorin rescue: mucositis, renal dysfunction, myelosuppresion, CNS toxicity, hepatic toxicity, GI toxicity
s-phase specific. disrupts folate-dependent processes for cell replication. inh DHFR, thymidylate synthase and GARFT. inh purine and thymidine synthesis
myelosuppression (give folic acid and vitamine B12 to reduce
rash- give dexamethasone 4mg PI BID x 3 days starting 1 day before treatment
vinca alkaloid MOA
vincristine, vinblastine, vinorelbine- binds to tubulin, inh of microtubule assembly. m-phase specific
docetaxel, paclitaxel- bind to tubulin, inhibit tubulin depolymerization. induce tubulin polymerization->inappropriate, stable, nonfunctional microtubules. m-phase specific
myelosuppresion, fluid retention syndrome (give dexamethasone 8mg PO BID x3 days starting the day before), alopecia, PN, myalgias/arthralgias
myelosuppresion, PN, myalgias/arthralgias, alopecia, hypersens rxn (give dexamethaxone 20mg IV or PO 12 adn 6 hrs proir to dose, diphenhydramine 50mg IV and ranitidine 50mg IV 30 mins before
binds to tubulin and promotes microtubule assembly and inh disassembly. pre-med with diphenhydramine 25mg, dexamethasone 8mg and ranitidine 50mg
Epothilones MOA (ixabepilone
bind to b-tubulin subunit leading to stabilization of microtubule function- m-phase specific. premed with diphenhydramine 50mg PO and ranitidine 150mg PO 1 hr prior
inhibits growth phase of microtubules-sequesters tubulin into non productive aggregates. G2/M cell-cycle block
irinotecan, topotecan- cell cycle non specific, but require ongoing DNA synthesis. binds Topo I, interfers with DnA synthesis.
diarrhea (acute-w/in 1 hr- atropin. delayed- antimotility agents)
myelosuppresion, alopecia, hyperbilirubinemia
epipodophyllotoxinc (etoposide) MOA
s and G2-phase specific. inhibits topo II by stabilizing the topoisomerase ii- DNA complex- prevents DNA unwind
doxorubicin, daunorubicin, epirubicin, adarubicin- topo II inh, DNA intercalation, free-radical formation
doxorubicin, daunorubicin, epirubicin, adarubicin- myelosuppresion, discolor urine, radiation recall, cardiac toxicities- acute: arrhythmias, pericarditis. chronic: cumulative injury to myocardium
mitoxantrone- topo II inhibitor, dna intercalation, low incidince of free-radical formation. cell cycle non specific
alkylating agent MOA
cyclophosphamide, ifosfamide, temozolomide, bendamustine
covalent bonding of highly reactive alkyl groups wwith nucleophilic groups of proteins and nucleic acids.
hemorrhagic cystisis, N/V, secondary malignancies, myelosuppresion, infertility, SIADH
hemorrhagic cystitis (give with mesna), hematuria, N/V, electrolyte wasting, alopecia, myelosuppresion, CNS toxicity (somnolence, confusion, hallucinations)
platinum analogues MOA
cisplatin, carboplatin, oxaliplatin
binds to DNA and forms intra- and inter-strand cross-links
PN, myelosuppresion, n/v/d, pharyngolaryngeal dysesthesia- prolong duration of infusion
hypersensitivty rxn (epinephrine, IV CCS, diphenhydramine), hyperglycemia, pancreatitis, coagulopahty and bleeding problems, inc BUN, dec alb
inhibits the message for cell division sent fromteh abnormal tyrosine kinase encoded by the philadelphia chromosome, prevening cell proliferation and inducing apoptosis
inhibits EGFR tyrosine kinase, leading to inhibition of EGFR autophosphorylation and signaling
multikinase inhibitors MOA
target multiple kinases to inhibit cancer cell proliferation and cause apoptosis. Sunitinib, sorafenib, pazopanib
temisirolimus, everlimus- binds to intracellular protein and inhibits mTOR that controls cell division
induce apoptosis, block growth factor receptors or induce anti-idotype antibodies
bleeding, GI perforation, hypertension, thrombolic event, proteinuria, arterial thrombosis
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