Pharmacogenetics Flashcards
(85 cards)
this drug was given to patients to tx TB and we saw initial neurological side effects
isoniazid
What detoxifies isoniazid?
N-acetyltransferase-2
Type of inheritance for NAT-2
autosomal recessive
inheritance pattern for slow acetylators are ______ for slow allele
Fast acetylators have ________copies of fast allele
-on NAT-2
homozygous
1 or 2 copies
People suffered severe hypotension following administration of the anti-hypertensive debrisoquine d/t
CYP2D6 Polymorphism
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%
How do we get ultrafast 2D6 metabolizer
up to 13 copies of the gene
What is our metabolite of debrisoquine
measure 4-OH DB
____ variants of 2D6 account for >90% of the poor metabolizers, making them excellent screeing targets
7
heterozygotes for poor/normal metabolizer of 2D6 are:
functionally reduced
how many copies of poor metabolizer do you need to express that phenotype of 2D6?
2 copies of poor metabolizer allele
Most antiD’s are handled by which CYP?
2D6
2D6 will both:
activate and inactivate the drug
2D6 handles what % of all drugs?
25%
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
This CYP polymorphism for poor metabolism of mephenytoin
2C19
2C19 homo.poor.met present in what % population
3-20%
CYP 2C19 responsible for metabolism of this anti-platelet drug
Does it activate it or break it down
Clopidogrel
Activates it
CYP 2C19 responsible for metabolism of this proton pump inhibitor
omeprazole
CYP 2C19 responsible for metabolism of this anti-convulsant
phenytoin
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
When would be a good time to use Clopidogrel?
to inhibit platelet aggregation
- cardiac cath
- CV stent
- Post MI
Those with even one slow allele (for CYP2C19) have less active drug and >50% increase in
_____ and ______ when taking clopidogrel
M.I. and stroke
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
