Q5 M4 TOXI LAB FINALS

Warfarin exerts its anticoagulant effect primarily by inhibiting which enzyme complex critical for vitamin K recycling?

• Gamma-glutamyl carboxylase

• Vitamin K epoxide reductase complex 1 (VKORC1)

• Cytochrome P450 3A4

• Vitamin K dehydrogenase

Which coagulation factors are functionally impaired first following warfarin administration, and why?

• Factor II and X — due to their shortest half-lives

• Factor VII — due to its shortest half-life (~4-6 hours)

• Proteins C and S — due to their slow synthesis

• Factor IX — because of hepatic metabolism

What genetic polymorphism strongly influences warfarin sensitivity and metabolism?

• CYP3A4*1B variant

• VKORC1 haplotype A and CYP2C9*2/*3 alleles

• Polymorphisms in Factor V Leiden

• MTHFR gene mutations

Following oral warfarin ingestion, why does the prothrombin time (PT)/INR have a delayed increase despite rapid absorption of the drug?

• Time needed for warfarin to inhibit platelet function

• Delay due to the half-life of pre-existing active coagulation factors, especially factor VII

• Slow intestinal absorption of warfarin metabolites

• Delay in hepatic uptake of warfarin

Which coagulopathy lab finding may paradoxically predispose to initial thrombotic events shortly after warfarin initiation?

• Increased protein C and S activity

• Decreased protein C and S activity preceding factor depletion

• Elevated fibrinogen levels

• Increased platelet aggregation

Warfarin toxicity management includes administration of vitamin K. Which of the following describes the kinetic relationship that limits the rapid reversal of anticoagulation despite vitamin K administration?

• Warfarin irreversibly binds coagulation factors

• Half-life of existing inhibited clotting factors delays hemostasis restoration

• Vitamin K promotes warfarin metabolism raising INR

• Vitamin K only neutralizes orally administered warfarin

Fresh frozen plasma (FFP) administration in warfarin toxicity primarily serves what purpose?

• To supplement vitamin K reserves

• To provide functional coagulation factors rapidly

• To directly inhibit warfarin activity

• To reduce INR by promoting protein C synthesis

Which of the following scenarios would warrant prophylactic vitamin K administration despite an elevated INR without bleeding?

• INR of 4.5 without bleeding in a patient with previous GI bleed

• INR of 5.5 in an otherwise healthy patient

• INR of 3.5 before surgery

• INR of 2.5 while starting anticoagulation

Superwarfarins used as rodenticides are significantly more potent than warfarin. What pharmacokinetic property primarily contributes to their increased toxicity?

• Extensive protein binding

• Longer half-life leading to prolonged half-life of anticoagulant effect

• Higher first-pass hepatic metabolism

• Reduced absorption from the gastrointestinal tract

Which of the following drugs is known to potentiate warfarin toxicity by inhibiting its metabolism?

• Rifampin

• Carbamazepine

• Amiodarone

• St. John’s Wort