Topoisomerase and Microtubule Inhibs

Question 1

Topoisomerase 1does what

Answer 1

single strand cut

Question 2

topoisomerase I attaches how

Answer 2

covalently

Question 3

how do topo 1 inhibitors work

Answer 3

covalently attach to topo 1 and glues it to the DNA, blocks religation

Question 4

how does topo 1 inhibitors form a physical barrier

Answer 4

barrier to replication and transcription
DNA breaks, protein glued, topo 1 inhib

Question 6

cells in what phase are most sensitive to topo 1 cleavage

Answer 6

S phase

Question 7

drug resistance mechanisms with topo 1 inhibs (4)

Answer 7

PGP overxpression
MRP overexpression
glutathione S transferase overexpression
topo downregulation

Question 8

topo 1 inhibitiors

Answer 8

topotecan
ironotecan

Question 9

what is ironotecan

Answer 9

topo 1 inhib

Question 10

ironotecan is a _____

Answer 10

prodrug

Question 11

ironotecan active metabolite metabolized by what

Answer 11

SN38 is metabolized by UGT1A1
if polymoprhism pts can have toxicity

Question 12

UGT1A1 polymorphism could make what drug toxic

Answer 12

ironotecan

Question 13

topo 2 does what

Answer 13

double strand cut
relieves torsional stress AND untangles DNA

Question 14

topoisomerase II is especially important for what

Answer 14

replication

Question 15

how do topoisomerase II inhibs work

Answer 15

lock the Topo II after double strand break covalently
double strand dna break
no religation anymore

Question 16

how does doxorubicin work

Answer 16

topo II inhibitor
free radical damages DNA
intercalator

Question 17

doxorubicin tox

Answer 17

cardiac toxicities due to low levels of enzymes that neutralize free radicals

Question 18

which drug has severe cardiotoxicity

Answer 18

doxorubicin, red devil

Question 19

how is cardiac toxicity from doxorubicin mediated

Answer 19

give dexrazoxane

Question 20

what causes cardiac toxicity in doxorubicin, what causes the free radicals?

Answer 20

iron catalyzed free radical formation

Question 21

etoposide class

Answer 21

topo II inhibitor

Question 22

etoposide cell cycle

Answer 22

G2

Question 23

etoposide does what

Answer 23

double strand break
does not have free radicals
does not intercalate

Question 24

which topoisomerase inhibitor is not sensitive to glutatione levels?

Answer 24

etoposide

Question 25

topo II resistance mechanisms (5)

Answer 25

PGP overexpression MRP overexpression glutathione S transferase overexpression - doxo only topo II downregulation increased DNA damage repair

Question 26

what does bleomycin do?

Answer 26

intercalates generates free iron radicals

Question 27

radical intermediate from bleomycin does what

Answer 27

single and double strand breaksb

Question 28

bleomycin side effect

Answer 28

pulmonary toxicity

Question 29

bleomycin which side effect not that bad

Answer 29

myelosupression

Question 30

bleomycin cell phase

Answer 30

G2/M

Question 31

where is bleomycin highest conc

Answer 31

skin and lung

Question 32

what do microtubules do

Answer 32

move chromosomal material into daughter cells during mitosis part of the spindle

Question 33

what phase are microtubules specific

Answer 33

G2/M

Question 34

how do microtubule destabilizers work

Answer 34

vinca alkaloids prevent assembly of microtubules bind tubulin

Question 35

how do microtubule stabilizers work

Answer 35

taxanes prevent disassembly of microtubules bind tubulin

Question 36

T/F: microtubule destabilizers and stabilizers bind at the same spot

Answer 36

F they bind different sites

Question 37

vinca alkaloids do what

Answer 37

inhibit microtubule assembly destabilizes

Question 38

vincristine toxicity

Answer 38

neurotoxicity peripheral neuropathy

Question 39

vinca alkyloid drug

Answer 39

vincristine

Question 40

destabilizer drugs

Answer 40

vincristine erubulin

Question 41

eribulin toxicity

Answer 41

lower rate of neurotoxicity

Question 42

microtubule stabilizer drugs

Answer 42

paclitaxel Ixabepilone

Question 43

paclitaxel class

Answer 43

stabilizer

Question 44

paclitaxel side effect

Answer 44

myelosupression

Question 45

ixabepilone class

Answer 45

stabilizer

Question 46

ixabeplilone PGP?

Answer 46

poor PGP substrates, not cross resistant with taxanes