Pharm2 11 Pharmacogenetics Flashcards
identify innovative drug targets; account for DNA sequence variation on drug effects, develop new agents
PharmacoGENOMICS
optimize drug efficacy, minimize drug toxicity via a genetic basis
PharmacoGENETICS
The basis of pharmacogenetics revolve around the existence of:
polymorphisms
Defined as genetic variations that occur in > 1% of population
Many involve cytochrome P450 isoenzyme
CYP2D6 drugs (5)
tricyclics, antidepressants, antiarrhythmics, β-receptor antagonists, codeine
CYP2C9 drugs (2)
warfarin, phenytoin
CYP2C19 drugs (2)
Omeprazole, clopidogrel
CYP2A6 drug
nicotine
Ethnic group (2) CYP2D6
Asians, African Americans
Ethnic groups CYP2C19
Asians
Ethnic groups CYP2A6
Asians
What may play a role in tobacco dependency in Asians?
CYPA6 pathway
Pathway problem?:
A 27 yo Asian patient returns to your practice for f/u 48 hours after having some minor surgery done. You had prescribed Tylenol #3, two tabs po q4h prn pain.
He is complaining of continued pain (pain scale 7/10), and is complaining of nausea, vomiting and GI distress.
Probable poor metabolizer, CYP2D6 variant.
Pathway problem?
A patient in your practice is s/p recent diagnosis of DVT. She was seen in the ER, given heparin followed by warfarin.
After 4 days, you get an INR to see if therapeutic. You find that this patient has an INR >6.
You administer vitamin K to help reverse the INR, but are in a quandary as to what is happening.
CYP2C9
Pathway problem?
A patient with newly diagnosed seizure disorder is placed on phenytoin.
After a week, you get your first set of phenytoin levels. The patient’s level is 26.
What are your thoughts?
Three big issues:
Possible CYP2C9 variance
Narrow therapeutic index of phenytoin
Capacity-limited pharmacokinetics of phenytoin.
Decrease dose, recheck levels, monitor for adverse reactions
PCR-RFLP testing may be needed
