Genomic Medicine Active Learning Exercise Flashcards
What is the key inactivating factor with warfarin?
CYP2C9
What is the therapeutic target for warfarin?
Vitamin K epoxide Reductase complex 1 when works upstream of clotting factors
62 y/o pt with prosthetic heart valve is prescribed the normal dose of warfarin for anticoagulant therapy. The patient has genotype CYP2C9*1*1. Will the patient clot, acheive therapeutic effect or bleed?
Patient will acheive therapeutic INR. This pt has the wild type CYP2C9, which is the enzyme that controls warfarin pharmacokinetic. So normal dose will put the pt in therapeutic range
Pt has mutation CYP2C9*3*3 what effect will this have on the warfarin pharmacokinetics?
Mutant allele for CYP2C9, so warfarin will be inactivated at a much slower rate.
Answer the picture
1 - B
2 - A
Will the patient with the mutant CYP*3*3 clot, achieve therapeutic level, or bleed?
Pt has only mutant alleles (decreased activity), so a normal dose would result in warfarin levels in this patient being higher than the normal. This patient would bleed.
62 y/o pt with a prosthetic heart valve is taking warfarin. This pt is also prescribed fluconazole (an anti-fungal that is also a CYP inhibitor). What will the effect be on the warfarin?
Since this is a CYP inhibitor, the warfarin will be metabolized more slowly. This patient will bleed.
What is the answer
1 - B
2 - A
62 y/o pt with a prosthetic heart valve is taking warfarin. This pt is also prescribed rifampin (CYP inducer). What will the effect be on the warfarin? Will this pt bleed, achieve therapeutic levels or clot when given a normal dose?
Rifampin will activate CYP leading to a faster inactivation of warfarin. A typical dose will cause this patient to clot.
What is genotype inhibition?
What a pt has a certain genetic makeup that leads them to be poor metabolizers of certain drugs, leading to longer drug half-life and higher plasma concentrations.
What is a genotype induction?
When a person’s genetic makeup makes them a rapid metabolizer of certain drugs. This will lead to lower plasma concentrations and a shorter half-life.
Patient with a prosthetic heart valve is prescribed a normal dose of warfarin for anti-coagulant therapy. This pt has a mutant VKORC1. What are the effects on the pharmacodynamics and will this pt clot, achieve therapeutic range, or bleed?
Mutant VKORC1 will not interact with warfarin as well as the Wt. Thus the warfarin will have no therapeutic effect, and this patient will clot (INR=1). This resistance may be overcome by increasing dosing of warfarin.
Patient with a prosthetic heart valve is prescribed a normal dose of warfarin for anti-coagulant therapy. This patient begins eating spinach salads twice daily. What will be the pharmacodynamic effects and will this patient clot, therapeutic range, or bleed?
Spinach is high in Vitamin K, which is converted to the normal substrate for VKORC1. Warfarin competes with the normal substrate. Vitamin K will out-compete warfain for binding and will have normal clotting.
What are the effects of Vitamin K on warfarin pharmacokinetics?
NONE!!
