PC3 Module 5.3 (PGx Clopidogrel/Statins)

CYP2C19 catalyzes the bioactivation of the prodrug ________________

A. clopidogrel

B. prasugrel

C. ticagrelor

A. clopidogrel

What is the predicted clinical function of these CYP2C19 alleles:

*1

A. normal function

B. no function (or loss of function)

C. increased function

A. normal function

What is the predicted clinical function of these CYP2C19 alleles:

*17

A. normal function

B. no function (or loss of function)

C. increased function

C. increased function

What is the predicted clinical function of these CYP2C19 alleles:

2-8

A. normal function

B. no function (or loss of function)

C. increased function

B. no function (or loss of function)

What is the phenotype given this genotype?

- 1/1

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

E. ultra rapid metabolizer

A. normal metabolizer

What is the phenotype given this genotype?

- 1/2, 1/3, 2/17

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

E. ultra rapid metabolizer

B. intermediate metabolizer

What is the impact on clopidogrel response given this genotype?

- 1/1

A. normal active metabolite levels

B. reduced active metabolite formation

C. significantly reduced active metabolite levels

D. normal or increased active metabolite levels

E. increased active metabolite levels

A. normal active metabolite levels

What is the phenotype given this genotype?

- 2/2, 2/3

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

E. ultra rapid metabolizer

C. poor metabolizer

What is the phenotype given this genotype?

- 1/17

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

E. ultra rapid metabolizer

D. rapid metabolizer

What is the phenotype given this genotype?

- 17/17

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

E. ultra rapid metabolizer

E. ultra rapid metabolizer

What is the enzyme activity given this genotype?

- 1/1

A. normal

B. reduced

C. absent

D. increased

E. markedly increased

A. normal

What is the enzyme activity given this genotype?

- 1/2, 1/3, 2/17

A. normal

B. reduced

C. absent

D. increased

E. markedly increased

B. reduced

What is the enzyme activity given this genotype?

- 2/2, 2/3

A. normal

B. reduced

C. absent

D. increased

E. markedly increased

C. absent

What is the enzyme activity given this genotype?

- 1/17

A. normal

B. reduced

C. absent

D. increased

E. markedly increased

D. increased

What is the enzyme activity given this genotype?

- 17/17

A. normal

B. reduced

C. absent

D. increased

E. markedly increased

E. markedly increased

What is the impact on clopidogrel response given this genotype?

- 1/2, 1/3, 2/17

A. normal active metabolite levels

B. reduced active metabolite formation

C. significantly reduced active metabolite levels

D. normal or increased active metabolite levels

E. increased active metabolite levels

B. reduced active metabolite formation

What is the impact on clopidogrel response given this genotype?

- 2/2, 2/3

A. normal active metabolite levels

B. reduced active metabolite formation

C. significantly reduced active metabolite levels

D. normal or increased active metabolite levels

E. increased active metabolite levels

C. significantly reduced active metabolite levels

What is the impact on clopidogrel response given this genotype?

- 1/17

A. normal active metabolite levels

B. reduced active metabolite formation

C. significantly reduced active metabolite levels

D. normal or increased active metabolite levels

E. increased active metabolite levels

D. normal or increased active metabolite levels

What is the impact on clopidogrel response given this genotype?

- 17/17

A. normal active metabolite levels

B. reduced active metabolite formation

C. significantly reduced active metabolite levels

D. normal or increased active metabolite levels

E. increased active metabolite levels

E. increased active metabolite levels

What alleles are associated with:

- less active metabolite

- decreased antiplatelet effects

- reduced clopidogrel effectiveness after PCI

A. normal

B. increased function

C. no function

C. no function

Clopidogrel treated CYP2C19 _________ and ___________ have increased risk for MACE

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

B. intermediate metabolizer

C. poor metabolizer

__________ and ____________ are not dependent on CYP2C19 for activation

A. clopidogrel

B. prasugrel

C. ticagrelor

B. prasugrel

C. ticagrelor

What drug:

- administered as prodrug

- contraindicated in patients with history of TIA or stroke

- irreversible P2Y12 inhibitor

A. clopidogrel

B. prasugrel

C. ticagrelor

B. prasugrel

What drug:

- direct acting, noncompetitive inhibitor

- reversibly binds to P2Y12 receptor

A. clopidogrel

B. prasugrel

C. ticagrelor

C. ticagrelor

Warning for what type of clopidogrel metabolizers:

- results in lower systemic active metabolite concentrations, lower antiplatelet response, and may result in higher CV risk. Consider use of another platelet P2Y12 inhibitor

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

B. intermediate metabolizer

C. poor metabolizer

What drug is indicated in the following patient:

- ACS and/or PCI patient

- CYP2C19 genotype: 1/17

A. clopidogrel

B. prasugrel or ticagrelor

A. clopidogrel

What drug is indicated in the following patient:

- ACS and/or PCI patient

- CYP2C19 genotype: 17/17

A. clopidogrel

B. prasugrel or ticagrelor

A. clopidogrel

What drug is indicated in the following patient:

- ACS and/or PCI patient

- CYP2C19 genotype: 1/1

A. clopidogrel

B. prasugrel or ticagrelor

A. clopidogrel

What drug is indicated in the following patient:

- ACS and/or PCI patient

- CYP2C19 genotype: 1/2

A. clopidogrel

B. prasugrel or ticagrelor

B. prasugrel or ticagrelor

What drug is indicated in the following patient:

- ACS and/or PCI patient

- CYP2C19 genotype: 2/2

A. clopidogrel

B. prasugrel or ticagrelor

B. prasugrel or ticagrelor

The evidence to date suppports CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed in patients with _____ or _______

ACS or PCI

CYP2C19 genotype ordered and returns as 1/2. In addition to aspirin, what antiplatelet therapy is appropriate? Patient has a history of TIA.

A. clopidogrel 75 mg once daily

B. clopidogrel 150 mg once daily

C. prasugrel 10 mg once daily

D. ticagrelor 90 mg twice daily

D. ticagrelor 90 mg twice daily

These statins are associated with what gene?

- atorvastatin

- fluvastatin

- lovastatin

- pitavastatin

- pravastatin

- rosuvastatin

- simvastatin

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

A. SLCO1B1

These statins are associated with what gene?

- rosuvastatin

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

B. ABCG2

These statins are associated with what gene?

- fluvastatin

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

C. CYP2C9

This association is with which gene?

- minor C allele associated with decreased statin clearance and increased statin exposure

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

A. SLCO1B1

This association is with which gene?

- associated with reduced transporter activity and increased rosuvastatin plasma levels

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

B. ABCG2

This association is with which gene?

- reduced function alleles increase exposure to fluvastatin

A. SLCO1B1

B. ABCG2

C. CYP2C9

D. CYP 2C19

C. CYP2C9

This gene is associated with what statin(s):

SLCO1B1

A. atorvastatin

B. fluvastatin

C. lovastatin

D. pitavastatin

E. pravastatin

F. rosuvastatin

G. simvastatin

A. atorvastatin

B. fluvastatin

C. lovastatin

D. pitavastatin

E. pravastatin

F. rosuvastatin

G. simvastatin

This gene is associated with what statin(s):

ABCG2

A. atorvastatin

B. fluvastatin

C. lovastatin

D. pitavastatin

E. pravastatin

F. rosuvastatin

G. simvastatin

F. rosuvastatin

This gene is associated with what statin(s):

CYP2C9

A. atorvastatin

B. fluvastatin

C. lovastatin

D. pitavastatin

E. pravastatin

F. rosuvastatin

G. simvastatin

B. fluvastatin

What phenotype does this SLCO1B1 genotype correlate to:

1/1

A. normal phenotype

B. decreased function

C. poor function

D. increased function

A. normal phenotype

What phenotype does this SLCO1B1 genotype correlate to:

1/5

A. normal phenotype

B. decreased function

C. poor function

D. increased function

B. decreased function

What phenotype does this SLCO1B1 genotype correlate to:

5/5

A. normal phenotype

B. decreased function

C. poor function

D. increased function

C. poor function

What implications does this SLCO1B1 genotype correlate to:

1/1

A. typical myopathy risk

B. increased statin exposure which may increase myopathy risk

C. no risk

A. typical myopathy risk

What implications does this SLCO1B1 genotype correlate to:

1/5

A. typical myopathy risk

B. increased statin exposure which may increase myopathy risk

C. no risk

B. increased statin exposure which may increase myopathy risk

What implications does this SLCO1B1 genotype correlate to:

5/5

A. typical myopathy risk

B. increased statin exposure which may increase myopathy risk

C. no risk

B. increased statin exposure which may increase myopathy risk

What recommendation does this SLCO1B1 genotype have:

1/1

prescribe desired starting dose of statin

For patients with the *1/*5 SLCO1B1 genotype, what drugs are recommended to be avoided (select all)

A. atorvastatin (or limit dose to <20 mg)

B. simvastatin (or limit dose to <20 mg)

C. lovastatin (or limit dose to <20 mg)

D. pitavastatin (or limit dose to <20 mg)

B. simvastatin (or limit dose to <20 mg)

C. lovastatin (or limit dose to <20 mg)

For patients with the *1/*5 SLCO1B1 genotype, what drugs are recommended to be limited in dose (select all)

A. atorvastatin (<= 40 mg)

B. simvastatin (<20 mg)

C. lovastatin (<20 mg)

D. pitavastatin (<=2 mg)

A. atorvastatin (<= 40 mg)

B. simvastatin (<20 mg)

C. lovastatin (<20 mg)

D. pitavastatin (<=2 mg)

For patients with the *5/*5 SLCO1B1 genotype, what drugs are recommended to be avoided (select all)

A. atorvastatin

B. simvastatin

C. lovastatin

D. pitavastatin

B. simvastatin

C. lovastatin

For patients with the 5/5 SLCO1B1 genotype, what is the dose recommendation for atorvastatin

A. <=20 mg

B. <=40 mg

C. <=1 mg

D. <= 30 mg

A. <=20 mg

For patients with the 5/5 SLCO1B1 genotype, what is the dose recommendation for fluvastatin

A. <=20 mg

B. <=40 mg

C. <=1 mg

D. <= 30 mg

B. <=40 mg

For patients with the 5/5 SLCO1B1 genotype, what is the dose recommendation for pitavastatin

A. <=20 mg

B. <=40 mg

C. <=1 mg

D. <= 30 mg

C. <=1 mg

For patients with the 5/5 SLCO1B1 genotype, what is the dose recommendation for pravastatin

A. <=20 mg

B. <=40 mg

C. <=1 mg

D. <= 30 mg

B. <=40 mg

For patients with the 5/5 SLCO1B1 genotype, what is the dose recommendation for rosuvastatin

A. <=20 mg

B. <=40 mg

C. <=1 mg

D. <= 30 mg

A. <=20 mg

What is the phenotype of a patient with this ABCG2 genotype?

- c.421 C/C

A. normal function

B. decreased function

C. poor function

D. increased function

A. normal function

What is the phenotype of a patient with this ABCG2 genotype?

- c.421 C/A

A. normal function

B. decreased function

C. poor function

D. increased function

B. decreased function

What is the phenotype of a patient with this ABCG2 genotype?

- c.421 A/A

A. normal function

B. decreased function

C. poor function

D. increased function

C. poor function

What are the implications of a patient with this ABCG2 genotype?

- c.421 C/C

A. typical myopathy risk

B. increased rosuvastatin exposure; unknown myopathy risk

C. no myopathy risk

A. typical myopathy risk

What are the implications of a patient with this ABCG2 genotype?

- c.421 C/A

A. typical myopathy risk

B. increased rosuvastatin exposure; unknown myopathy risk

C. no myopathy risk

B. increased rosuvastatin exposure; unknown myopathy risk

What are the implications of a patient with this ABCG2 genotype?

- c.421 A/A

A. typical myopathy risk

B. increased rosuvastatin exposure; unknown myopathy risk

C. no myopathy risk

B. increased rosuvastatin exposure; unknown myopathy risk

What are the recommendations for a patient with this ABCG2 genotype?

- c.421 C/C

A. prescribe desired starting dose

B. prescribe <=20 mg as starting dose, if dose >20 mg needed for desired effect, consider alternative statin or adding a non-statin

C. no myopathy risk

A. prescribe desired starting dose

What are the recommendations for a patient with this ABCG2 genotype?

- c.421 C/A

A. prescribe desired starting dose

B. prescribe <=20 mg as starting dose, if dose >20 mg needed for desired effect, consider alternative statin or adding a non-statin

C. no myopathy risk

A. prescribe desired starting dose

What are the recommendations for a patient with this ABCG2 genotype?

- c.421 A/A

A. prescribe desired starting dose

B. prescribe <=20 mg as starting dose, if dose >20 mg needed for desired effect, consider alternative statin or adding a non-statin

C. no myopathy risk

B. prescribe <=20 mg as starting dose, if dose >20 mg needed for desired effect, consider alternative statin or adding a non-statin

What is the phenotype of a patient with this CYP2C9 genotype?

- 1/1

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

A. normal metabolizer

What is the phenotype of a patient with this CYP2C9 genotype?

- 1/2, 1/3

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

B. intermediate metabolizer

What is the phenotype of a patient with this CYP2C9 genotype?

- 2/3, 3/3

A. normal metabolizer

B. intermediate metabolizer

C. poor metabolizer

D. rapid metabolizer

C. poor metabolizer

What are the implications of a patient with this CYP2C9 genotype?

- 1/1

A. normal exposure

B. increased fluvastatin exposure; may translate to increased myopathy risk

A. normal exposure

What are the implications of a patient with this CYP2C9 genotype?

- 2/3, 3/3

A. normal exposure

B. increased fluvastatin exposure; may translate to increased myopathy risk

B. increased fluvastatin exposure; may translate to increased myopathy risk

What are the recommendations for a patient with this CYP2C9 genotype?

- 1/1

A. prescribe desired starting dose

B. prescribe <=40 mg/day as starting dose

C. prescribe <=20 mg/day as starting dose

A. prescribe desired starting dose

What are the recommendations for a patient with this CYP2C9 genotype?

- 1/2, 1/3

A. prescribe desired starting dose

B. prescribe <=40 mg/day as starting dose

C. prescribe <=20 mg/day as starting dose

B. prescribe <=40 mg/day as starting dose

What are the implications of a patient with this CYP2C9 genotype?

- 1/2, 1/3

A. normal exposure

B. increased fluvastatin exposure; may translate to increased myopathy risk

B. increased fluvastatin exposure; may translate to increased myopathy risk

What are the recommendations for a patient with this CYP2C9 genotype?

- 2/3, 3/3

A. prescribe desired starting dose

B. prescribe <=40 mg/day as starting dose

C. prescribe <=20 mg/day as starting dose

C. prescribe <=20 mg/day as starting dose

Atorvastatin (40 mg daily) was prescribed to a patient. The patient has the SLCO1B1 1/5 genotype. What atorvastatin dose is most appropriate?

A. avoid atorvastatin

B. 20 mg

C. 40 mg

D. 80 mg

C. 40 mg

What is the most appropriate rosuvastatin dose for a patient with the SLCO1B1 5/5 genotype?

A. <= 20 mg

B. <= 40 mg

C. <= 1 mg

A. <= 20 mg