Mechanism of Action
Phytomenadione acts in the liver at the molecular level. For plasma clotting factors to bind calcium ions ($Ca^{2+}$), they must contain negatively charged gamma-carboxyglutamic acid residues.
The drug is converted into its active form — hydroquinone, which functions as a coenzyme. It mediates the $\gamma$-carboxylation of glutamic acid residues within the structure of clotting factors. During this reaction, active vitamin K is converted into an inactive epoxide. Normally, this epoxide must be reduced back into the active cycle by specific enzymes (epoxide reductase and vitamin K reductase). It is this exact reduction process that is blocked by indirect anticoagulants.
Pharmacological Effects
The primary effect of the drug is hemostatic. Phytomenadione restores normal levels of functional procoagulants: prothrombin (factor II), as well as factors VII, IX, and X.
Additionally, vitamin K is essential for the synthesis of natural anticoagulants (proteins C and S) and the bone calcium-binding protein — osteocalcin. Because coagulation factors have a short half-life and are rapidly degraded, replenishing vitamin K deficits quickly eliminates the cause of bleeding.
Indications
The primary goal of administration is the management and prevention of hemorrhagic syndromes associated with hypoprothrombinemia:
- Overdose of indirect anticoagulants (vitamin K antagonists). Phytomenadione serves as their specific antidote.
- Liver and biliary tract pathology: hepatitis, cirrhosis, and obstructive jaundice (lack of bile impairs the intestinal absorption of this fat-soluble vitamin).
- Malabsorption syndrome (sprue, enterocolitis, Crohn's disease).
- Prevention of hemorrhagic disease of the newborn (infants have inadequate dietary vitamin $K_1$ intake and lack the intestinal flora needed to synthesize $K_2$).
- Preoperative preparation before major surgical procedures.
Side Effects and Contraindications
Administration of phytomenadione may be accompanied by allergic reactions, including skin rash, pruritus, erythema, and bronchospasm.
Particular caution must be exercised during intravenous administration due to a high risk of severe anaphylactoid reactions.
Note: Unlike the water-soluble provitamin $K_3$ (menadione sodium bisulfite), phytomenadione does not possess the same level of specific toxicity in newborns (lower risk of hemolytic anemia and hyperbilirubinemia).
Clinical Administration and Prescription
Because phytomenadione is a fat-soluble drug, the presence of bile is critical for its normal gastrointestinal absorption. In obstructive jaundice, oral administration is ineffective, and parenteral routes are required.
The drug is administered orally as an oily solution in capsules of 0.01–0.02 g per dose.
Prescription Example: Rp.: Sol. Phytomenadioni oleosae 10% in caps. 0.01 D.t.d. N. 20 S. Take 1–2 capsules daily by mouth.