CYPs Flashcards
NSAIDs
CYP2C9
Tacrolimus
Immunosuppressant used in transplantation; low bioavailability (due to CYP3A4 and 3A5 metabolism); low TI
CYP3A5 polymorphism => pharmacokinetic variation
- no activity (most whites) => receive standard dose
- extensive activity (most blacks) => 1.5-2x standard dose
Codeine
prodrug activated by CYP2D6 to form morphine
CYP2D6 polymorphism => pharmacokinetic variation
- poor metabolizers (7% whites) => reduced analgesia
- ultrarapid metabolizers => adverse effects of morphine OD
Clopidogrel (Plavix)
CYP2C19
Diazepam (and other “-azepam” benzos)
CYP2C19
Midalozam (and other “-azolam” benzos)
CYP3A4
Ethanol
CYP2E1
Proton pump inhibitors (“-prazoles”)
CYP2C19
CNS drugs (SSRIs like fluoxetine)
CYP2D6
CYPs affected by echinacea
CYP3A4 induced
CYP1A2 inhibited
Thiopurine
Prodrug that requires conversion to thioguanine for anticancer activity; inactivated by TPMT for excretion
TPMT polymorphism => pharmacokinetic variation
- poor metabolizers (rare) => increased risk of bone marror suppression
Metoprolol
CYP2D6
Warfarin
Anticoagulation activity via inhibition of vitamin K synthesis (VKORC1); inactivated by CYP2C9
CYP2C9 variation => pharmacokinetic variation
- *2 and *3 alleles are reduced function => reduced dose
VKORC1 variation => pharmacodynamic variation
- haplotype A => reduced dose
CYPs inhibited by furanocoumarins
CYP3A4
Clopidogrel
prodrug activated via two CYP2C19 oxidation steps to form active anti-platelet drug
CYP2C19 polymorphism => pharmacokinetic variation
- reduced function *2 and *3 => less antiplatelet effect and increased risk of thrombosis/MI/stroke