antimetabolites

Question 1

5 fluorouracil: how does it work and who can’t take it

Answer 1

activated by dihydropyramidine dehydrogenase

active agents and targets

FdUMP–> binds TS + 5N10N-MTHF
FdUTP–> incorporated into DNA, inhibits synthesis/function
FUTP–> incorporated into RNA, inhibits all that

ppl w/autosomal recessive disorder for mutated DHPD (enzyme at top)

Question 2

the prodrug of 5 FU

Answer 2

capecitabine: works the way 5 FU works, but metabolized to 5FU by thymidine phosophorlyase

Question 3

applications for capecitabine and 5FU

Answer 3

capecitabine- breast cancer

5FU- colorectal cancer

Question 4

capecitabine in the xelox regimen

Answer 4

xelox is capecitane and cisplatin: first line treatment for metastatic colorectal cancer

Question 5

thymidylate inhibitors

Answer 5

FdUMP (5FU), capecitabine, TAS-102

Question 6

TAS-102

Answer 6

prodrug whose metabolites consist of trifluridine and tipiracil

Question 7

trifluridine

Answer 7

metabolite of 5FU: a fluorinated pyrimidine nucleoside analog

assimilated into DNA and inhibits its synthesis/function

Question 8

tipiraceil

Answer 8

a metabolite of TAS-102

thymidine phosphorylase inhibitor
TP inhibition leads to higher levels of trifluridine

Question 9

thymidine phosphorylase, thymidine synthase, DPD

Answer 9

thymidine phosphorylase- metabolizes capecitabine to 5FU
DPD- a thymidine phosphorylase inhibitor
thymidine synthase- inhibited by 5FU

Question 10

deoxyctidine analogs

Answer 10

cytarabine and gemcitabine, S phase inhibitors

Question 11

cytarabine: MOA, metabolites

Answer 11

converted to a 5-mononucleotide “ara-CMP” by deoxycytidine kinase. Ara CMP is built up to a triphosphate “Ara CTP”

ara-CTP is the main metabolite

Question 12

ara-CTP

Answer 12

main cytotoxic tri-phosphorylated metabolite of cytarabine:

1) inhibits DNA polymerase beta and alpha –> blockade on DNA.
2) assimilated into DNA and blocks chain elongation, produces defective DNA fragments
3) incorporated into RNA

Question 13

application of ara-CTP

Answer 13

hematological maligs, AML acute myelogenous leukemia NHL non-hodgkin’s lymphoma

Question 14

gemcitabine: kinetics

Answer 14

phosphorylated by deoxycytabine kinase to a monophosphate form, then other kinases build it up to a triphosphate form

Question 15

gemcitabine: MOA of active metabolite

Answer 15

gemcitabine triphosphate: inhibits DNA polymerase alpha and beta, and incorporated into DNA itself

gemcirtabine diphosphate: inhibits ribonucleotide reductase.

Question 16

gemcitabine targets

Answer 16

NHL, hetamological.

Question 17

purine antagonists drugs

Answer 17

6-thiopurines (6-mercaptopurine(6 MP) and 6 thioguanine (6-TG))

fludarabine

Question 18

6 thiopurines

Answer 18

6 mercaptopurine, 6 thioguanine

Question 19

6 thiopurines MOA

Answer 19

metabolized by thiopurine methyltransferase (TMPT) to 6MP and 6TG

6MP–> metabolized by HGPRT to monophosphate-6-thioinosinic acid (MP6TP)

inhibits de novo purine nucleotide synthesis

Question 20

excessive 6mp toxicity can be induced by combining 6TP with what?

Answer 20

allopurinol, which blocks xanthine oxidase

Question 21

6 mp is for what

Answer 21

acute leukemias