Fitzpatrick - Anti-Neoplastic Drugs, Antimitotic and G/M Phase Drugs

Question 1

MOA of vinca drugs

Answer 1

INHIBIT tubulin ELONGATION/polymerization by binding to Beta tubulin subunits at forming end –> fraying continues to shorten microtubule.
- Rate of depolymerization (fraying)&raquo_space;» rate of polymerization (assembly).

Question 2

MOA of taxane drugs

Answer 2

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

Question 3

General classification of vinca alkaloids and taxane drugs.

Answer 3

Cell cycle specific, acting in M phase

Question 4

Adverse effects of vincristine.

Answer 4

neurotoxicity

Vincristine neuropathy&raquo_space;» vinblastine neurpathy

Question 5

Why does tx with vinca and taxane drugs often lead to MDR/tx failure?

Answer 5

Due to increased P-glycoprotein expression.

- Nullifies effect of drugs with MOA involving internal sites/processes.

Question 6

Route of vinca and taxane admin.
Location of metabolization.
Route of excretion.

Answer 6

Admin via IV.
Metab in liver.
Excreted in bile and feces.

Question 7

MOA of Topoisomerase inhibitors

Answer 7

Binds to DNA-enzyme complex and creates a “persistently cleavable complex”.

Question 8

General classification of Topoisomerase I inhibitors

Answer 8

Cell cycle specific, acting in S phase

Question 9

General classification of Topoisomerase II inhibitors

Answer 9

Cell cycle non-specific

Question 10

Doxorubicin (anthracycline class) MOA and toxicity - end product that damages DNA and related toxicity.

Answer 10

Superoxide and H2O2:

1) Damages tumor DNA
2) Toxicity - dilated cardiomyopathy, HF.

Question 11

Adverse effect of bleomycin.

Answer 11

Skin and lung damage (tissues do not have hydrolase to metabolize bleo).

Question 12

Bleomycin MOA and toxicity - end product that damages DNA and related toxicity.

Answer 12

Bleomycin –> DNA-Bleomycin Fe2+ –> DNA-Bleomycin Fe3+ –> superoxide and hydroxyradicals..

1) damage DNA
2) Lung damage - dyspnea, rales, dry cough, infiltrate –> fibrosis.

Question 13

Unique toxicities:

1) Pitting edema, difficulty breathing = ?drug toxicity
2) Lung fibrosis on CSR or imagnign = ? drug toxicity

Answer 13

1. Doxorubicin

2. Bleomycin

Question 14

Cancer drugs with what MOA are not prone to P-gp MDR? (**i.e. monoclonal antibodies)

Answer 14

Cannot/does not effect drugs with MOA involving exterior cell surface.