Pharm - Antitumor Abx/Plant Alkaloids

Question 1

Ant-tumor abx

Answer 1

anthracyclines (doxorubicin)

bleomycin, dactinomycin, mitomycin

Question 2

plant alkaloids

Answer 2

Topoisomerase I inhibitors
Vinca alkaloids
Taxanes

Question 3

Topoisomerase I inhibitors

Answer 3

irinotecan

topotecan

Question 4

vinca alkaloids

Answer 4

vinCRistine

vinBLastine

vinorelbine

Question 5

taxanes

Answer 5

paclitaxel

docetaxel

Question 6

anthracyclines

MOA

Answer 6

passive diffusion of unionized drug into cells

all nucleated cells can rapidly accumulate drug

intercalate DNA - accumulates in nucleus

topoisomerase II inhibitor

Question 7

anthracyclines clearance

Answer 7

mostly liver

monitor bilirubin

Question 8

anthracyclines

major dose-limiting side effect

Answer 8

myelosuppression (neutropenia)

Question 9

anthracyclines

Answer 9

myelosuppression
alopecia
N/V
Urine
Vesicant

Question 10

cardiotoxicity w/ anthracycline use

Answer 10

undergo 1 or 2 electron reductions to reactive compounds

oxygen radical formation

(semiquinone +O2=O2 free radical)

uses Fe3+ to form reactive species (OH-)

acute: EKG changes, arrhythmias
chronic: cumulative doses LVEF, dilation, congestion, effusions

Question 11

____ is more susceptible to the oxidative damage caused by anthracyclines

Answer 11

myocardium

has dec endogenous antioxidant enzymes (glutathione)

Question 12

preventative cardioprotection during anthracycline use

Answer 12

• weekly admin (versus q3week) to avoid high peaks
• chelating agent
• liposomal products

Question 13

dexrazoxane

Answer 13

hydrolyzed to EDTA-derived analog

chelator, binds intracellular Fe to dec free radical formed w/ anthracycline use

FDA approved - metastatic breast cancer

GIVEN W/I 30 MIN OF DOXORUBICIN

Question 14

dexrazoxane AE

Answer 14

myelosuppression
alopecia
mucositis
N/V
diarrhea 

*unsure if via dexrazoxane alone or combo w/ anthracycline

Question 15

liposomal anthracyclines

Answer 15

Doxil

avoids high peak concentrations of anthracyclines

(avoids free radical damage, cardiotoxicity)

Question 16

anthracycline resistance

Answer 16

• active efflux from cells (MDRp170)
• altered topoisomerase II
• altered free radical biochem (inc glutathione - antioxidant)

Question 17

daunorubicin/idarubicin use

Answer 17

leukemias

Question 18

doxorubicin/epirubicin use

Answer 18

breast

lymphomas

Question 19

dactinomycin use

Answer 19

Wilm’s
Ewing’s
germ cell

Question 20

bleomycin use

Answer 20

hodkins
sclerosis for pleural effusions
lung tox

Question 21

mitomycin-C use

Answer 21

bladder cancer
anal cancer
long nadir (4-6 wks)

Question 22

camptothecins

Answer 22

irinotecan

topotecan

Question 23

topotecan use

Answer 23

ovarian

Question 24

irinotecan use

Answer 24

GI

Question 25

topotecan AE

Answer 25

- neutropenia - thrombocytopenia - GI (mild): mucositis, N/V/D - alopecia - rash - elevated LFTs

Question 26

irinotecan AE

Answer 26

- neutropenia - thrombocytopenia - eosinophilia - GI * DIARRHEA (cholinergic) -N/V, alopecia, asthenia, anorexia, fatigue, inc LFTs, bilirubin, term rxn

Question 27

irinotecan 2 types of main GI side effect

Answer 27

- early onset=cholinergic syndrome, tx w/ atropine | - late onset=SN-38 metabolite, changes in gut epithelium

Question 28

topo I inhibitor resistance

Answer 28

- reduced drug accumulation - altered intracellular drug distribution - altered carboxyl esterase activity - dec levels of topo I (dec transcription, mutations) - low S-phase fraction of cancer cells

Question 29

topo I

Answer 29

S-phase -relaxes supercoiled DNA by creating transient single-strand nicks to allow unwinding for DNA replication and RNA transcription. - promotes movement of the replication fork and provides genomic stability. - once replication complete, religates DNA strands

Question 30

vinca alkaloids

Answer 30

vinCRistine vinBLastine Vinorelbine

Question 31

vinca alkaloids MOA

Answer 31

- disturb MT formation | - other mechanisms also prob involved (DNA, RNA, protein synthesis, inhib glycolysis, etc)

Question 32

vinca alkaloids w/ significant neuropathy

Answer 32

vinCristine

Question 33

vinca alkaloids w/ significant myelosuppresion

Answer 33

vinBlastin

Question 34

vincristine uses

Answer 34

non-hodgkins lymphoma | ALL

Question 35

vinorelbine uses

Answer 35

NSCLC breast cancer

Question 36

vinblastin uses

Answer 36

Hodgkin's disease | testicular cancer

Question 37

taxanes MOA

Answer 37

enhances MT polymerization can't break down, blocks cell cycle @ metaphase/anaphase transition

Question 38

taxanes AE

Answer 38

- myelosuppression - neuropathies - infusion-related rxns - hand-foot syndrome (docetaxcel)