Anticoagulant rodenticides exert their toxic effects by which mechanism?

• A. Inhibition of vitamin K epoxide reductase
• B. Uncoupling oxidative phosphorylation
• C. Glycine receptor antagonism
• D. Inhibition of acetylcholinesterase

Answer: (A)

Inhibiting vitamin K epoxide reductase is the mechanism behind anticoagulant rodenticides. These compounds block the enzyme that regenerates reduced vitamin K, so the cycle of vitamin K is halted. Without sufficient active vitamin K, the liver cannot gamma-carboxylate glutamate residues on the vitamin K–dependent coagulation factors (II, VII, IX, X) and their regulatory proteins C and S. As a result, these factors become inactive and the clotting cascade fails, leading to a bleeding tendency.

Clinically, this effect tends to present as prolonged bleeding, with the earliest laboratory sign often being an extended PT because factor VII has the shortest half-life. The effect is not immediate; existing clotting factors are gradually depleted as they turn over. Treatment involves giving vitamin K to replenish the cycle and, if bleeding is present, providing plasma or other clotting factor sources.

Other listed mechanisms describe different toxic actions (uncoupling of oxidative phosphorylation, glycine receptor antagonism, acetylcholinesterase inhibition) and do not explain how anticoagulant rodenticides disrupt coagulation.