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Flashcards in Anticancer Drugs Deck (43):
1

most important efflux pump responsible for multidrug resistance

p-glycoprotein aka multidrug resistant protein 1 (MDR1)

2

cell cycle specific agents

B-AMEC

Bleomycin
Antimetabolites
Microtubule inhibitors
Epipodophyllotoxins
Camptothecins

3

what are the cell cycle non specific agents

Alkylating Agents
Platinum coordination complexes
Antitumor antibiotics (minus Bleomycin)

4

what are the antimetabolites

Folate analogues: Methotrexate

Purine analogues: 6-mercaptopurine and 6-thioguanine

Pyrimidine analogues: Fluoropyrimidines (5-fluorouracil and capecitabine) and Deoxycytidine analogues (cytarabine and gemcitabine)

5

what inhibits the renal excretion of methotrexate

CANP

Cephalosporin
Aspirin
NSAIDs
Penicillin

6

mechanism of action of methotrexate

catalyzed by folylpolyglutamate synthetase to MTX polyglutamate --> inhibits dihydrofolate reductase --> no THF --> needed for deoxythymidylate nucleotides and purine nucleotides

7

what drug is used in conjunction with MTX and why

Leucovorin, derivative of THF, to rescue normal cells from toxicity and overcome accidental drug overdose

8

adverse effects of MTX

a lot can be resolved with leucovorin

Myelosuppression
Pulmonary Fibrosis

9

mechanism of 6-mercaptopurine

converted to 6-MP ribose phosphate (or thio-inosinic acid or TIMP) by HGPRT --> inhibits phosphoribosyl pyrophosphate amidotransferase --> needed for de novo purine synthesis

10

what drugs/deficiency can make 6-mercaptopurine toxic

-it is metabolized by xanthine oxidase so if given with allopurinol which inhibits the enzyme then 6-MP will reach toxic level if dose not reduced

-also metabolized by TPMT (thiopurine methyltransferase) so if deficiency in allele, 6-MP can reach toxic levels if dose not reduced

11

mechanism of thioguanine

converted to nucleotide thioguanosine monophosphate (TGMP) by HGPRT
-inhibits PRPP amidotransferase which inhibits purine synthesis
-inhibits Guanylate kinase so can't go from GMP to GDP
-can be converted to TGTP and dTGTP which can be incorporated into RNA and DNA respectively

12

what can make a normal dose of thioguanine toxic

TPMT (thiopurine methyltransferase) deficiency hence thioguanine dose must be reduced

it is inactivated by deamination (not oxidation) so xanthine oxidase (allopurinol) does not play a role here

13

when treating adult acute leukemia, what drug is thioguanine used synergistically with

Cytarabine

14

first line drug for colorectal cancer

5-fluorouracil

15

mechanism of 5-fluorouracil

converted to FdUMP which forms a tertiary complex with thymidylate synthase and reduced folate (N5, N10, and methylene THF) --> inhibition of DNA synthesis

16

what potentiates the activity of 5-fluorouracil

increasing level of the reduced folate - N5, N10, and methylene THF

17

what can cause a normal dose of 5-fluorouracil to become toxic

deficiency of dihydropyrimidine dehydrogenase (DPD), the enzyme that metabolized it

18

adverse effects of 5-fluorouracil

hand foot syndrome (also seen in capecitabine)

19

what catalyzes capecitabine

thymidine phosphorylase

20

the enzyme thymidine phosphorylase is high in what cancers (name drug metabolized by enzyme)

breast and colorectal cancer

(capecitabine)

21

mechanism of cytarabine

converted to cytosine arabinoside triphosphate
-inhibits DNA pol alpha (DNA synthesis)
-inhibits DNA pol beta (DNA repair)
-incorporated into chain --> termination

22

how is cytarabine inactivated

by deamination in the intestinal mucosa

23

mechanism of gemcitabine

-converted to gemcitabine diphosphate which inhibits ribonucleotide reductase --> reduces nucleotide needed for DNA synthesis

-converted to gemcitabine triphosphate which incorporates into chain and causes termination

24

how is gemcitabine eliminated

deaminated to difluorodeoxyuridine which is excreted in urine

25

adverse effect of gemcitabine

renal microangiopathy syndromes like HUS (hemolytic uremic syndrome) and TTP (thrombotic thrombocytopenic purpura)

26

what are the anticancer microtubule inhibitors and what does inhibiting microtubules do

Vinca Alkaloids: Vinblastine and Vincristine
Taxanes: Docetaxel and Paclitaxel


inhibits formation of mitotic spindles needed for cell division to daughter cells and also microtubules are needed for cellular functions such as movements, phagocytosis, and axonal transport

27

mechanism of vinca alkaloids (name them)

Vinblastine and Vincristine

they bind to beta-tubulin and stops it from polymerizing with alpha-tubulin to form microtubules

28

adverse of vincristine

Paralytic Ileus
Peripheral Neuropathy
Optic Atrophy
SIADH

29

mechanism of Taxanes (name them)

Docetaxel and Paclitaxel

they bind to beta-tubulin (different site from vinca alkaloids) --> promote microtubule polymerization and inhibit depolymerization --> arrest cells in mitosis --> apoptosis

30

condition requiring reduced dose of taxanes (name them)

Docetaxel and Paclitaxel

liver dysfunction

31

adverse effect seen in Paclitaxel and how it is avoided

hypersensitivity reactions

avoided with premedication with dexamethasone, diphenhydramine, and H2 blocker

32

what is Abraxane and its importance

albumin bound Paclitaxel formulation approved for metastatic cancer that is not associated with hypersensitivity reactions hence no need for premedication with dexamethasone, diphenhydramine, and H2 blocker

33

what are the Epipodophyllotoxins

Etoposide
Teniposide

34

mechanism of action of epipodophyllotoxins (name them)

Etoposide and Teniposide

inhibits topoisomerase II --> DNA damage through strand breakage

35

what are the Camptothecins

Irinotecan
Topotecan

36

mechanism of Camptothecins (name them)

Irinotecan and Topotecan

inhibits topoisomerase I --> needed for cutting religating single DNA strands

37

what is the more potent form of Irinotecan and how are they eliminated

SN-38 (converted in the liver)

both eliminated in bile and feces

38

adverse effects of Irinotecan

diarrhea with two forms
-1st: within 24 hours and due to cholinergic activity so stop with atropine
-2nd: within 2 to 10 days and can lead to electrolyte imbalance and dehydration

39

what are the antitumor antibiotics

BADD

Bleomycin
Anthracyclines: Daunorubicin and Doxorubicin

40

mechanism of bleomycin

binds to DNA --> free radical formation via Fe dependent process--> single and double strand breaks --> inhibition of DNA biosynthesis

41

adverse effect of bleomycin

pulmonary fibrosis

42

mechanism of anthracyclines (name them)

Daunorubicin and Doxorubicin

inhibits topoisomerase II

43

adverse effects of anthracyclines (name them)

Daunorubicin and Doxorubicin

Cardiotoxicity: 2 form
-acute: 2-3 days and is usually transient and asymptomatic
-chronic: due to increased free radicals within the myocardium and is treated/prevented with iron chelating agent dexrazoxane

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