EpistemisPhytonadione (Vitamin K1)
Common trade names: Konakion, Mephyton.
Mechanism
Pharmacological Group and Molecular Target
Synthetic lipophilic cofactor for the carboxylation of vitamin K-dependent coagulation factors.
Detailed Mechanism of Action
Cumarine anticoagulants (such as warfarin) and superwarfarin rodenticide insecticides (such as brodifacoum) act by blocking the enzyme vitamin K epoxide reductase (VKORC1). This prevents the reconversion of inactive vitamin K (epoxide form) back to its reduced active form (vitamin K hydroquinone). When the reduced form is depleted, the post-translational gamma-carboxylation of the glutamic acid residues of the hepatic synthesis coagulation factors II, VII, IX and
Exogenous phytonadione administered at high doses is a biologically active isomer that is capable of bypassing the enzymatic blockade of VKORC1 by being reduced by an alternative enzymatic pathway insensitive to warfarin (such as the NAD(P)H-dependent enzyme quinone reductase), restoring normal concentrations of reduced vitamin K to resume the synthesis of new functional coagulation factors.
Indicators and dose
Specific Clinical Indications
- Reversal of excessive anticoagulation by warfarin or coumarin derivatives in patients with active bleeding or with an international normalized ratio (INR) greater than 10 without clinical bleeding.
- Accidental or autolytic poisoning by long-acting rodenticides ("superwarfarins" such as brodifacoum).
Dosage Scheme and Infusion Protocols
- Reversal of Elevated INR with Major Bleeding (Adult): Administer 10 mg of Phytonadione slowly intravenously diluted in 50 mL of physiological saline to infuse in a time not less than 30 minutes strictly. Rapid intravenous infusion is associated with severe fatal anaphylaxis reactions of immunological origin. It should always be associated with Prothrombin Complex Concentrate (PCC) or fresh frozen plasma for immediate rescue hemostasis (since the synthesis effect of vitamin K1 takes between 6 and 12 hours to be effective).
- Superwarfarin overdose: Requires prolonged massive oral doses of phytonadione of up to 50 mg to 100 mg daily for several weeks or months, due to the extremely long tissue elimination half-life of the rodenticide from the body (months).
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Antidotes and Toxicology
- Cluster
- Coagulation Synthesis Co-Factor