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Flashcards in Pharmacogenetics Deck (85)
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1

this drug was given to patients to tx TB and we saw initial neurological side effects

isoniazid

2

What detoxifies isoniazid?

N-acetyltransferase-2

3

Type of inheritance for NAT-2

autosomal recessive

4

inheritance pattern for slow acetylators are ______ for slow allele
Fast acetylators have ________copies of fast allele
-on NAT-2

homozygous
1 or 2 copies

5

People suffered severe hypotension following administration of the anti-hypertensive debrisoquine d/t

CYP2D6 Polymorphism

6

Poor metabolizer of CYP2D6 inheritance was:
w/ mutant allele frequency of:
and a poor metabolizer frequency in the population of:

autosomal gene, (75 variants!!!)
30%
2-10%

7

How do we get ultrafast 2D6 metabolizer

up to 13 copies of the gene

8

What is our metabolite of debrisoquine

measure 4-OH DB

9

____ variants of 2D6 account for >90% of the poor metabolizers, making them excellent screeing targets

7

10

heterozygotes for poor/normal metabolizer of 2D6 are:

functionally reduced

11

how many copies of poor metabolizer do you need to express that phenotype of 2D6?

2 copies of poor metabolizer allele

12

Most antiD's are handled by which CYP?

2D6

13

2D6 will both:

activate and inactivate the drug

14

2D6 handles what % of all drugs?

25%

15

Patient is put on anti-D with known 2D6 activation for metabolism of drug.... w/in 1-2 weeks patient complains of severe side effects, why?

patient is POOR metabolizer, and is most likely CYP2D6 poor metabolizer homologous thus is building up a lot of drug right away

16

This CYP polymorphism for poor metabolism of mephenytoin

2C19

17

2C19 homo.poor.met present in what % population

3-20%

18

CYP 2C19 responsible for metabolism of this anti-platelet drug
Does it activate it or break it down

Clopidogrel
Activates it

19

CYP 2C19 responsible for metabolism of this proton pump inhibitor

omeprazole

20

CYP 2C19 responsible for metabolism of this anti-convulsant

phenytoin

21

How can being a poor metabolizer of CYPC219 be of benefit when taking omeprazole

bc will alter response of proton pump inhibition and poor metabolizers have higher drug levels which correlates with increased gastric pH and higher cure rates

22

When would be a good time to use Clopidogrel?

to inhibit platelet aggregation
-cardiac cath
-CV stent
-Post MI

23

Those with even one slow allele (for CYP2C19) have less active drug and >50% increase in
_____ and ______ when taking clopidogrel

M.I. and stroke

24

What is a complication of taking aspirin and clopidogrel post MI?

Patients are often prescribed a PPI to help with reflux. The PPI is often omeprazole which uses CYP2C19 as does clopidogrel (anti-coAg) and the two drugs will compete with each other
--higher rate of death and reoccurance of MI if you take the two together

25

What is key for the poor metabolizer phenotype of CYP2C9

2 low activity alleles
2C9*2 and 2C9*3

26

Together *2 and/or *3 are in up to what % of patients

31%

27

CYP polymorphism that will impact metabolism of Warfarin

2C9

28

Warfarin functions as

anti-coagulant

29

consequence of excessive warfarin?
not enough?

excessive bleeding
excessive clotting and could lead to stroke

30

benefits of genetic testing for 2C9

good for warfarin dosing
-prevents 85,000 serious bleeding events
-prevents 17,000 strokes