Antimetabolites Flashcards

1
Q

what do anti-metabolites inhibit?

A

production of building blocks

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2
Q

what phase of cell cycle do anti-metabolites block?

A

S phase

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3
Q

how do antimetabolites act

A

mimic substrates and cofactors
require biotransformation

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4
Q

nuclobase vs nucleotide vs nucleotide

A

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

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5
Q

purine structure

A

two rings

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6
Q

pyrimidine structure

A

smaller (one ring)

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7
Q
A

adenine

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8
Q
A

guanine

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9
Q
A

cytosine

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10
Q
A

thymine

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11
Q
A

uracil

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12
Q

2 ways pyrimidine interferes with metabolism

A

interfere with pyrimidine nucleotide synthesis
inhibit DNA polymerase

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13
Q

5-FU interferes with what

A

thymidine synthesis from uracil

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14
Q

how does 5-FU work

A

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

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15
Q

5-FU traps what enzyme

A

thymidylate synthase
covalent inhibitor

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16
Q

toxicity from 5-FU treatament

A

thymidine treatment

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17
Q

resistance mechanisms 5-FU

A

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

18
Q

genetic factor in 5-FU

A

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

19
Q

how to increase efficacy with 5-FU

A

give Leucovorate
folate cofactor
increases amount of ternary complex

20
Q

cytosine analogs do what

A

inhibit DNA synthesis

21
Q

cytarabine target

A

DNA polymerase alpha

22
Q

cytarabine class

A

antimetabolite

23
Q

cytarabine converted to what

A

Ara-C

24
Q

Ara-C is a _____ of DNA polymerase alpha

A

competitive inhibitor

25
Q

what cancers is cytarabine useful in

A

CNS - lymphoma nad leukemia

26
Q

cytidine deaminase levels are what in the CNS

A

low

27
Q

what is given with cytarabine to incrase efficacy

A

tetrahydrouridine

28
Q

what does tetrahydrouridine do

A

inhibits cytidine deaminase

29
Q

6-mercaptopurine does what

A

blocks synthesis of purine nucleotides
inhibits multiple enzymes

30
Q

6-MP resistance

A

loss of HGPRT which activates 6-MP

31
Q

6-MP interactions

A

allopurinol increases toxicity
TPMT polymorphism increases toxicity

32
Q

allopurinol interacts with what drugs

A

6-mercaptopurine

33
Q

folate is what vitamin

A

B9

34
Q

what do antifolates target

A

dihydrofolate reductase (DHFR)

35
Q

what does DHFR target

A

reduces to tetrahydrofolate which is protein synthesis and base synthesis

36
Q

methotrexate looks like what

A

folic acid

37
Q

methotrexate resistance mechanisms (two)

A

amplification of DHFR gene
decreased polyglutamation

38
Q

methotrexate target

A

DHFR

39
Q

methotrexate overdose treated with what

A

leucovorin

40
Q

leucovorate does what in methotrexate tox

A

reverses toxic effects of DHFR inhibition

41
Q

leucovorin multiple effects

A

reverse methotrexate overdose
enhance 5-FU activity