Microtubule Agents, Cell Cycle Inhibitors

Question 1

Antimitotic anticancer agents disrupt which phase of the cell cycle?

Answer 1

M phase

Question 2

Antimitotics (vinca alkaloids, taxanes, epothilones) exert their effects by disruption of __ dynamics

Answer 2

microtubule

Question 3

What happens to tubules during cell division?

Answer 3

alternating periods of elongation and shortening

Question 4

ixabepilone is what drug class?

Answer 4

epothilone

Question 5

Which drug class INHIBITS the ASSEMBLY of microtubules?

Answer 5

vinca alkaloids

vincristine, vinblastine, vinorelbine

Question 6

Which two drug classes PROMOTE microtubule assembly and INHIBIT disassembly?

Answer 6

taxanes
epothilone (ixabepilone)

stabilize microtubules

Question 7

What mediates resistance to vinca alkaloids?

Answer 7

MDR1 and P-gp

Question 8

Pts with what disorder should have dose reductions of vinca alkaloids?

Answer 8

hepatic dysfunction

Question 9

Approximately half of US children with cancer who get chemotherapy will be given what drug?

Answer 9

vincristine

Question 10

What is the most significant dose limiting toxicity of vincristine?

Answer 10

peripheral neuropathy

Question 11

Where should vinca alkaloids NEVER be injected

Answer 11

CSF

Inadvertent injection of vinca alkaloids into the CSF causes a devastating and often fatal irreversible coma and seizures

Question 12

What toxicity is associated with vinblastine?

Answer 12

myelosuppression (leukopenia)

usually reaches its maximum 7-10 days post dose with recovery ~ 7 days after maximum myelosuppression is reached

Question 13

Does vinblastine have severe neurological side effects?

Answer 13

no

Question 14

What toxicity is associated with vinorelbine?

Answer 14

granulocytopenia

neurotoxicity typically mild

Question 15

Which drug class has a tricyclic core?

Answer 15

taxanes

fused to oxetane ring and a beta phenylisoserine ester

Question 16

Which taxane is more lipophilic?

Answer 16

paclitaxel

Question 17

A hydroxyl group at what carbon enhances the solubility of docetaxel?

Answer 17

C10

Question 18

A modified side chain at what carbon of docetaxel and cabazitaxel causes enhanced cytotoxic potency?

Answer 18

C13

Question 19

How do taxanes interrupt cell division?

Answer 19

form large and dense aberrant structures

Question 20

Which drug class binds polymerized β-tubulin of microtubules promoting a stable conformation that promotes elongation and inhibits depolymerization?

Answer 20

taxanes

Question 21

Taxanes are substrates of what transporter?

Answer 21

P-gp

efflux via P-gp contributes to resistance

Question 22

What is the major metabolite of paclitaxel?

Answer 22

6 alpha hydroxypaclitaxel

Question 23

What CYP forms the major metabolite of paclitaxel?

Answer 23

2C8

Question 24

Which taxane is O-demethylated at C10 and C7 by CYP3A4/5?

Answer 24

cabazitaxel

forms three active metabolites including docetaxel

Question 25

Most taxane metabolites are excreted via what route?

Answer 25

biliary

Question 26

Which taxane has very limited water solubility?

Answer 26

paclitaxel

Question 27

Which taxane is administered in a vehicle of 50% ethanol and 50% polyethoxylated castor oil?

Answer 27

paclitaxel causes hypersensitivity rxns

Question 28

What must pts on paclitaxel be premedicated with?

Answer 28

H1 antagonist H2 antagonist glucocorticoid

Question 29

A formulation of paclitaxel bound to ___ has better water solubility and does not require pretreatment.

Answer 29

albumin

Question 30

Caution should be used when co-administering paclitaxel with drugs that compete for what CYP?

Answer 30

2C ex. ethinyl estradiol, diazepam

Question 31

Which has better solubility paclitaxel or docetaxel?

Answer 31

docetaxel can be used with more tolerable vehicle (polysorbate 80)

Question 32

What is required for pretreatment with docetaxel?

Answer 32

glucocorticoid (dexamethasone) required to prevent t progressive fluid retention

Question 33

What reduces P-gp affinity of cabazitaxel resulting in longer retention in tumor cells and improved BBB penetration?

Answer 33

methyl ethers

Question 34

Which taxane is formulated with polysorbate 80, but does NOT cause fluid retention?

Answer 34

cabazitaxel

Question 35

Which is less susceptible to P-gp mediated drug resistance, taxanes or epothilones?

Answer 35

epothilones (ixabepilone)

Question 36

What enhances the metabolic stability of ixabepilone relative to epothilone B?

Answer 36

lactam replacement

Question 37

Ixabepilone has very good water solubility. a. true b. false

Answer 37

b. false like paclitaxel, ixabepilone has very limited water solubility

Question 38

What part of ixabepilone formulation causes hypersensitivity reactions?

Answer 38

50% polyethoxylated castor oil