Genetics E2- Pharmacogenomics

Pharmacokinetics or pharmacodynamics: genes affecting drug processing (absorption, breakdown, CYP450 enzymes)

Pharmacokinetics

Pharmacokinetics or pharmacodynamics: genes affecting drug targets (receptors)

Pharmacodynamics

What drugs are metabolized by CYP2D6?

Codeine & Nortriptyline

What is a prodrug?

Inactive substance is metabolized to it’s active form

What is an active drug?

Metabolism eliminates the effect of the drug

What drugs are prodrugs?

Codeine, Clopidogrel,

What drugs are active drugs?

Nortriptyline, Warfarin, Thiopurines (6-MP)

How would poor CYP2D6 metabolizers respond to codeine at standard doses?

Drug not converted to active form → No analgesic effect

How would poor CYP2D6 metabolizers respond to nortriptyline at standard doses?

Slower drug clearance → Higher drug levels → Increased SEs, possible OD

How would ultra-rapid CYP2D6 metabolizers respond to codeine at standard doses?

Faster & more extensive conversion to active form → Higher levels of morphine → Possible OD; shower duration of pain control

How would ultra-rapid CYP2D6 metabolizers respond to Nortriptyline at standard doses?

Faster drug clearance → little to no therapeutic effect

What drug is metabolized by CYP2C19?

Clopidogrel

In the case of a patient lacking a functioning CYP2C19 enzyme, what medication should be substituted for clopidogrel?

Ticagrelor

What genotyping is recommended for patients receiving stents?

CYP2C19

What drug is metabolized by CYP2C9?

*CYP2C9*2 & CYP2C9*3 variants result in decreased clearance

Warfarin

Patients with CYP2C9*2 & CYP2C9*3 variants require a ________ dose of warfarin to maintain their target INR & minimize risk of bleeding.

Lower

What drugs are metabolized by TPMT?

Thiopurines (6-MP)

How would a poor metabolizer of TPMT respond to 6-MP?

Decreased metabolism → myelosuppression, pancytopenia