PGx

Question 1

What does SLCO1B1 polymorphism affect?

Answer 1

Codes for OATP protein which facilitates hepatic uptake of all statins for metabolism

Question 2

What are the actionable phenotypes possible for SLCO1B1?

Answer 2

Decreased/possibly decreased function
Poor function

Question 3

Which statins require alternatives if the patient is tested decreased SLCO1B1 function?

Answer 3

Lovastatin
Simvastatin
or limit dose for both

Question 4

What is the dose-related risk for rosuvastatin?

Answer 4

Myopathy risk if doses >20 mg

Question 5

What does ABCG2 polymorphism affect?

Answer 5

Encodes BCRP that exports statin into the ECF

Question 6

Which statin is affected by two genetic polymorphisms?

Answer 6

Rosuvatstain (SLCO1B1 & ABCG2)
Fluvastatin (SLCO1B1 & 2C9)

Question 7

In general, what should we limit rosuvastatin dose to?

Answer 7

≤20 mg as starting dose

Question 8

When do we limit rosuvastatin dose to ≤10 mg/day?

Answer 8

SLCO1B1 DF + ABCG2 PF
SLCO1B1 PF + ABCG2 PF

Question 9

What are the two HLAs genotypes that affect carbamazepine?

Answer 9

HLA-B15:02
HLA-A31:01

Question 10

If a person is tested HLA-B*15:02, what anti-epileptics should be avoided?

Answer 10

Carbamazepine
Oxcarbazepine
Phenytoin
Lamotrigine
Phenobarbital

Question 11

What is the difference between the skin reactions detected by the two genotypes for carbamazepine?

Answer 11

HLA-B15:02 - SJS/TEN
HLA-A31:01 - mainly MPE, some SJS/TEN & DRESS

Question 12

What is the genotype that predicts abacavir-related hypersensitivity?

Answer 12

HLA-B*57:01

Question 13

What predicts allopurinol-induced hypersensitivity?

Answer 13

Renal impairment
Concomitant diuretics
High starting dose (>100 mg/day)
HLA-B*58:01
Rapid dose escalation
Elderly

Question 14

What are the antidepressants affected by 2D6 polymorphism?

Answer 14

Amitriptyline & nortriptyline
Paroxetine
Fluvoxamine
Venlafaxine
Vortioxetine

Question 15

What are the actionable phenotypes for 2D6?

Answer 15

URM
NM
IM
PM

Question 16

Which antidepressant is affected by both 2D6 and 2C19 polymorphism?

Answer 16

Amitriptyline

Question 17

Why is nortriptyline not affected by 2C19 polymorphism?

Answer 17

2C19 metabolises amitriptyline to nortriptyline

Question 18

What is the general recommendation for 2D6 URMs on antidepressants?

Answer 18

Ami: switch or increase dose
Paroxetine: switch
Fluvoxamine: no data
Venla: increase dose
Vortioxetine: switch or increase dose

Question 19

Which antidepressants require dose reduction in 2D6 IMs?

Answer 19

Amitriptyline (25%)
Paroxetine

Question 20

Which antidepressants are recommended to be switched to an alternative drug for 2D6 PMs?

Answer 20

Amitriptyline (or reduce dose)
Venlafaxine
Fluvoxamine (or reduce dose)
Vortioxetine (or reduce dose)

Question 21

What are the actionable phenotypes for 2C19?

Answer 21

URM
RM
NM
IM
PM

Question 22

Which antidepressant may be kept at the same dose for 2C19 URM & RM?

Answer 22

Sertraline

Question 23

What are the general recommendations for 2C19 PMs on antidepressants?

Answer 23

Switch to alternative drug or use 50% lower starting dose

Question 24

What is the general starting dose of antidepressants for 2C19 IMs?

Answer 24

Standard dose

Question 25

Which SSRIs are not primarily cleared via 2C19?

Answer 25

Fluoxetine Fluvoxamine Paroxetine

Question 26

What are the recommendations for individuals with 2D6 IM & 2C19 IM?

Answer 26

25% lower starting dose for Amitriptyline

Question 27

What ie the difference between recommendations for clopidogrel between different indications?

Answer 27

ACS/PCI: IM or PM to use prasugrel/ticagrelor Stroke/TIA: IM or PM to use ticagrelor/ticlopidine

Question 28

What are the recommendations for 2C19 URM & RM using clopidogrel for ACS/PCI indications?

Answer 28

Use standard dose

Question 29

When do we consider higher doses for PPIs in 2C19 polymorphisms

Answer 29

URM: 100% higher doses for all RM/NM: consider higher doses if H pylori or esophagitis

Question 30

What is the metabolite for tramadol?

Answer 30

O-desmethyltramadol via 2D6

Question 31

What is the metabolite for codeine?

Answer 31

Morphine via 2D6

Question 32

When do we need to avoid tramadol or codeine?

Answer 32

2D6 URM or PM

Question 33

What are the recommendations for SLCO1B1 & ABCG2 polymorphisms for rosuvastatin?

Answer 33

DF: Standard dose PF: Limit to 20 mg starting dose. Consider combining or alternative if higher doses needed