PGx Flashcards
What does SLCO1B1 polymorphism affect?
Codes for OATP protein which facilitates hepatic uptake of all statins for metabolism
What are the actionable phenotypes possible for SLCO1B1?
Decreased/possibly decreased function
Poor function
Which statins require alternatives if the patient is tested decreased SLCO1B1 function?
Lovastatin
Simvastatin
or limit dose for both
What is the dose-related risk for rosuvastatin?
Myopathy risk if doses >20 mg
What does ABCG2 polymorphism affect?
Encodes BCRP that exports statin into the ECF
Which statin is affected by two genetic polymorphisms?
Rosuvatstain (SLCO1B1 & ABCG2)
Fluvastatin (SLCO1B1 & 2C9)
In general, what should we limit rosuvastatin dose to?
≤20 mg as starting dose
When do we limit rosuvastatin dose to ≤10 mg/day?
SLCO1B1 DF + ABCG2 PF
SLCO1B1 PF + ABCG2 PF
What are the two HLAs genotypes that affect carbamazepine?
HLA-B15:02
HLA-A31:01
If a person is tested HLA-B*15:02, what anti-epileptics should be avoided?
Carbamazepine
Oxcarbazepine
Phenytoin
Lamotrigine
Phenobarbital
What is the difference between the skin reactions detected by the two genotypes for carbamazepine?
HLA-B15:02 - SJS/TEN
HLA-A31:01 - mainly MPE, some SJS/TEN & DRESS
What is the genotype that predicts abacavir-related hypersensitivity?
HLA-B*57:01
What predicts allopurinol-induced hypersensitivity?
Renal impairment
Concomitant diuretics
High starting dose (>100 mg/day)
HLA-B*58:01
Rapid dose escalation
Elderly
What are the antidepressants affected by 2D6 polymorphism?
Amitriptyline & nortriptyline
Paroxetine
Fluvoxamine
Venlafaxine
Vortioxetine
What are the actionable phenotypes for 2D6?
URM
NM
IM
PM
Which antidepressant is affected by both 2D6 and 2C19 polymorphism?
Amitriptyline
Why is nortriptyline not affected by 2C19 polymorphism?
2C19 metabolises amitriptyline to nortriptyline
What is the general recommendation for 2D6 URMs on antidepressants?
Ami: switch or increase dose
Paroxetine: switch
Fluvoxamine: no data
Venla: increase dose
Vortioxetine: switch or increase dose
Which antidepressants require dose reduction in 2D6 IMs?
Amitriptyline (25%)
Paroxetine
Which antidepressants are recommended to be switched to an alternative drug for 2D6 PMs?
Amitriptyline (or reduce dose)
Venlafaxine
Fluvoxamine (or reduce dose)
Vortioxetine (or reduce dose)
What are the actionable phenotypes for 2C19?
URM
RM
NM
IM
PM
Which antidepressant may be kept at the same dose for 2C19 URM & RM?
Sertraline
What are the general recommendations for 2C19 PMs on antidepressants?
Switch to alternative drug or use 50% lower starting dose
What is the general starting dose of antidepressants for 2C19 IMs?
Standard dose
Which SSRIs are not primarily cleared via 2C19?
Fluoxetine
Fluvoxamine
Paroxetine
What are the recommendations for individuals with 2D6 IM & 2C19 IM?
25% lower starting dose for Amitriptyline
What ie the difference between recommendations for clopidogrel between different indications?
ACS/PCI: IM or PM to use prasugrel/ticagrelor
Stroke/TIA: IM or PM to use ticagrelor/ticlopidine
What are the recommendations for 2C19 URM & RM using clopidogrel for ACS/PCI indications?
Use standard dose
When do we consider higher doses for PPIs in 2C19 polymorphisms
URM: 100% higher doses for all
RM/NM: consider higher doses if H pylori or esophagitis
What is the metabolite for tramadol?
O-desmethyltramadol via 2D6
What is the metabolite for codeine?
Morphine via 2D6
When do we need to avoid tramadol or codeine?
2D6 URM or PM
What are the recommendations for SLCO1B1 & ABCG2 polymorphisms for rosuvastatin?
DF: Standard dose
PF: Limit to 20 mg starting dose. Consider combining or alternative if higher doses needed
