Antimetabolites

Question 1

what do anti-metabolites inhibit?

Answer 1

production of building blocks

Question 2

what phase of cell cycle do anti-metabolites block?

Answer 2

S phase

Question 3

how do antimetabolites act

Answer 3

mimic substrates and cofactors
require biotransformation

Question 4

nuclobase vs nucleotide vs nucleotide

Answer 4

base - base
side - sugar
tide - sugar and phosphate, cant get in cell w pos charge

Question 5

purine structure

Answer 5

two rings

Question 6

pyrimidine structure

Answer 6

smaller (one ring)

Question 7

Answer 7

adenine

Question 8

Answer 8

guanine

Question 9

Answer 9

cytosine

Question 10

Answer 10

thymine

Question 11

Answer 11

uracil

Question 12

2 ways pyrimidine interferes with metabolism

Answer 12

interfere with pyrimidine nucleotide synthesis
inhibit DNA polymerase

Question 13

5-FU interferes with what

Answer 13

thymidine synthesis from uracil

Question 14

how does 5-FU work

Answer 14

uracil analog with fluorine on
fDUMP doesn’t allow thymidylate synthase to remove H
thymidylate trapped in ternary complex and no DNA syntheis

Question 15

5-FU traps what enzyme

Answer 15

thymidylate synthase
covalent inhibitor

Question 16

toxicity from 5-FU treatament

Answer 16

thymidine treatment

Question 17

resistance mechanisms 5-FU

Answer 17

upregulation thymidylate synthase
downregulation activating enzymes converting 5-FU to fDUMP

Question 18

genetic factor in 5-FU

Answer 18

polymorphisms in DPD, can’t break down 5-FU and toxicity occurs

Question 19

how to increase efficacy with 5-FU

Answer 19

give Leucovorate
folate cofactor
increases amount of ternary complex

Question 20

cytosine analogs do what

Answer 20

inhibit DNA synthesis

Question 21

cytarabine target

Answer 21

DNA polymerase alpha

Question 22

cytarabine class

Answer 22

antimetabolite

Question 23

cytarabine converted to what

Answer 23

Ara-C

Question 24

Ara-C is a _____ of DNA polymerase alpha

Answer 24

competitive inhibitor

Question 25

what cancers is cytarabine useful in

Answer 25

CNS - lymphoma nad leukemia

Question 26

cytidine deaminase levels are what in the CNS

Answer 26

low

Question 27

what is given with cytarabine to incrase efficacy

Answer 27

tetrahydrouridine

Question 28

what does tetrahydrouridine do

Answer 28

inhibits cytidine deaminase

Question 29

6-mercaptopurine does what

Answer 29

blocks synthesis of purine nucleotides inhibits multiple enzymes

Question 30

6-MP resistance

Answer 30

loss of HGPRT which activates 6-MP

Question 31

6-MP interactions

Answer 31

allopurinol increases toxicity TPMT polymorphism increases toxicity

Question 32

allopurinol interacts with what drugs

Answer 32

6-mercaptopurine

Question 33

folate is what vitamin

Answer 33

B9

Question 34

what do antifolates target

Answer 34

dihydrofolate reductase (DHFR)

Question 35

what does DHFR target

Answer 35

reduces to tetrahydrofolate which is protein synthesis and base synthesis

Question 36

methotrexate looks like what

Answer 36

folic acid

Question 37

methotrexate resistance mechanisms (two)

Answer 37

amplification of DHFR gene decreased polyglutamation

Question 38

methotrexate target

Answer 38

DHFR

Question 39

methotrexate overdose treated with what

Answer 39

leucovorin

Question 40

leucovorate does what in methotrexate tox

Answer 40

reverses toxic effects of DHFR inhibition

Question 41

leucovorin multiple effects

Answer 41

reverse methotrexate overdose enhance 5-FU activity