Lecture 23/24 Pharmacogenomics Flashcards
What are areas of potential PGx factors in CV therapy?
A: anticoagulants - warfarin and other VKAs
B: antiplatelets - clopidogrel
C: statins - atorvastatin, simvastatin
D: BBs - metoprolol, carvedilol, propranolol
What resource is good for looking at PGx factors in treatment?
PharmGKB
For CYP2C19 what are gene alleles and resulting phenotypes, and what does the distribution look like race wise?
Alleles: 1 - normal fxn,, 2 - loss of fxn,, 3 - loss of fxn,, 17 - gain of fxn,,, Phenotype: 1/1 - normal metabolism
1/2 or 1/3 - intermediate metabolism,, 2/2 or 2/3 or 3/3 - poor metabolism
1/17 - rapid metabolism
17/17 - ultrarapid metabolism
Races: Whites - 2% poor, 25% intermediate, 40% rapid or ultra
Blacks - 4% poor, 30% intermediate, 45% rapid or ultra
Asian - 14% poor, 50% intermediate, <5% rapid or ultra
What is SLCO1B1, what drug does it affect, and what are the phenotypes to look out for?
is a transporter/enzyme/receptor found in hepatocytes aka OATP1B1/OAT1B1/OCT1B1 and affects atorvastatin, lovastatin, and simvastatin transport ⇒ decrease in fxn = increased risk of statin-induced myopathy,, Phenotypes: Increased fxn = 14/14
Normal = 1/1, 1/14
Decreased: 1/5, 1/15
Possible Decreased: 5/6, 10/15, 5/43
Poor = 5/5, 15/15, 5/15
What are dosage recommendations regarding when SLCO1B1 function is decreased/possible decrease or poor for statins?
Atorvastatin: when decreased prescribe </= 40 mg as start and adjust,, if poor fxn prescribe </= 20 mg as start and adjust
Lovastatin: when decreased or poor prescribe an alternative statin
Simvastatin: when decreased or poor prescribe an alternative statin
Pitavastatin: when decreased prescribe </= 2 mg to start and adjust,, if poor prescribe </= 1 mg to start and adjust
Pravastatin: when decreased can prescribe desired starting dose - no adjustment
if poor prescribe </= 40 mg to start and adjust
What enzyme affects several beta-blockers, and specifically which beta-blocker more than others, and are there any dosing changes that are recommended with different phenotypes?
CYP2D6 affects BBs including carvedilol, propranolol, and heavily metoprolol ⇒ 70-80% of the oral dose is transformed
if CYP2D6 is poor or ultrarapid preferably metoprolol should be avoided, but if ultrarapid it can still be used at target dose, whereas if poor metabolizer therapy should be initiated with lowest recommended starting dose carefully titrating upward as needed
