Flashcards in Fitzpatrick - Anti-Neoplastic Drugs, Antimitotic and G/M Phase Drugs Deck (14)
MOA of vinca drugs
INHIBIT tubulin ELONGATION/polymerization by binding to Beta tubulin subunits at forming end --> fraying continues to shorten microtubule.
- Rate of depolymerization (fraying) >>>> rate of polymerization (assembly).
MOA of taxane drugs
STABILIZE microtubules by binding to Beta-tubulin on forming end. Reach negative/fraying end and inhibit depolymerization by ENHANCING TUBULIN POLYMERIZATION AND (hyper)STABILIZE MICROTUBULES... unabated assembly
General classification of vinca alkaloids and taxane drugs.
Cell cycle specific, acting in M phase
Adverse effects of vincristine.
Vincristine neuropathy >>>> vinblastine neurpathy
Why does tx with vinca and taxane drugs often lead to MDR/tx failure?
Due to increased P-glycoprotein expression.
- Nullifies effect of drugs with MOA involving internal sites/processes.
Route of vinca and taxane admin.
Location of metabolization.
Route of excretion.
Admin via IV.
Metab in liver.
Excreted in bile and feces.
MOA of Topoisomerase inhibitors
Binds to DNA-enzyme complex and creates a "persistently cleavable complex".
General classification of Topoisomerase I inhibitors
Cell cycle specific, acting in S phase
General classification of Topoisomerase II inhibitors
Cell cycle non-specific
Doxorubicin (anthracycline class) MOA and toxicity - end product that damages DNA and related toxicity.
Superoxide and H2O2:
1) Damages tumor DNA
2) Toxicity - dilated cardiomyopathy, HF.
Adverse effect of bleomycin.
Skin and lung damage (tissues do not have hydrolase to metabolize bleo).
Bleomycin MOA and toxicity - end product that damages DNA and related toxicity.
Bleomycin --> DNA-Bleomycin Fe2+ --> DNA-Bleomycin Fe3+ --> superoxide and hydroxyradicals..
1) damage DNA
2) Lung damage - dyspnea, rales, dry cough, infiltrate --> fibrosis.
1) Pitting edema, difficulty breathing = ?drug toxicity
2) Lung fibrosis on CSR or imagnign = ? drug toxicity