PGx Lecture 6

Question 1

CYP2C19 metabolizes

Answer 1

PPI (omemprazole)

Clopidogrel

Question 2

What phenotype is of the most concern

Answer 2

PM

Question 3

What ethic group has the most PM for CYP2C19

Answer 3

Asians (20-25%)

Question 4

Is clopidogrel a prodrug

Answer 4

YES -> requires metabolism to be active and produce anticoag effects

Question 5

CYP2C19 alleles

Answer 5

• 1: wild type
• 2: 681G -> A; splicing defect, NO activity
• 3: 363G -> A; premature stop codon, NO activity
• 17: gain of function, but no activity score

Question 6

What alleles account for more PM phenotypes in Asian populations

Answer 6

*2 and *3

Question 7

Does CYP2C19 have activity scores

Answer 7

NO

Question 8

Clopidogrel works by irreversibly binding

Answer 8

to platelet ADP P2Y12

Question 9

In general population, up to _______% of pts demonstrate some level of resistance to clopidogrel

Answer 9

30%

Question 10

Is genotype solely responsible for metabolism

Answer 10

NO. DDI can also up or down regulate metabolism

Question 11

Taking a PPI can ________ activity

Answer 11

REDUCE

Question 12

Platelet aggregation while taking clopidogrel is considered

Answer 12

therapeutic failure

Question 13

New anticoag that doesn’t require CYP2C19 for activation

Answer 13

Prasugrel

Question 14

Alternatives to clopidogrel for PM

Answer 14

high dose clopidogrel

prasugrel

Question 15

Dosing for UM, EM, IM, PM

Answer 15

UM: standard dose
EM: standard dose
IM: alternative drug
PM: alternative drug

Question 16

PM phenotype for CYP2C19

Answer 16

2/2, 2/3, 3/3

Question 17

It is always important to consider what simultaneously

Answer 17

drug-gene and drug-drug interactions

Question 18

are there dose-dependent SE for clopidogrel

Answer 18

No

Question 19

An IM taking an PPI will become a

Answer 19

PM

Question 20

PGx Tests for CYP2C19

Answer 20

DMET plus (Affymetrix): multiple variants of CYP2C19
Roche AmpliChip CYP450 Test: multiple variants of CYP2C19

Question 21

FDA black box warning for clopidogrel (plavix)

Answer 21

reduced effectiveness in pts who are PM of clopidogrel; informs health care professionals that a genetic test is available