Phytonadione (Vitamin K1)
**Phytonadione (Vitamin K1)** is a synthetic, lipid-soluble vitamin identical to naturally occurring Vitamin K1. It is a critical antidote in veterinary medicine, primarily utilized to reverse coagulopathies caused by the ingestion of **anticoagulant rodenticides** (e.g., warfarin, brodifacoum, bromadiolone). Key clinical applications include: * **Anticoagulant Rodenticide Toxicity:** The mainstay of therapy. Second-generation rodenticides have a very long half-life, often requiring 3-4 weeks of continuous Vitamin K1 supplementation. * **Sweet Clover Poisoning:** Used in ruminants to treat dicumarol toxicity from moldy sweet clover. * **Hepatic Disease:** Used adjunctively in acute liver failure or biliary obstruction where Vitamin K absorption or utilization is impaired. * **Sulfaquinoxaline Toxicity:** Reverses bleeding disorders associated with this coccidiostat. > **Clinical Pearl:** Vitamin K1 (phytonadione) is effective for these toxicities, whereas Vitamin K3 (menadione) is ineffective and carries a higher risk of toxicity. Phytonadione requires 6-12 hours to synthesize new clotting factors; therefore, actively bleeding patients require immediate plasma or whole blood transfusions to provide active coagulation factors.
Mecanismo: Phytonadione is essential for the hepatic synthesis of **Vitamin K-dependent coagulation factors (Factors II, VII, IX, and X)**. * **Mechanism:** In the liver, inactive precursors of these factors require γ-carboxylation of their glutamic acid residues to become functional. This carboxylation is catalyzed by the enzyme **γ-glutamyl carboxylase**, which requires the reduced form of Vitamin K (Vitamin K hydroquinone) as a cofactor. * **The Vitamin K Cycle:** During carboxylation, Vitamin K is oxidized to Vitamin K epoxide. The enzyme **Vitamin K epoxide reductase (VKOR)** recycles the epoxide back to the active hydroquinone form. * **Anticoagulant Rodenticides →** inhibit VKOR, depleting active Vitamin K and halting the production of functional clotting factors. Exogenous phytonadione bypasses this blockade, providing the necessary substrate to resume factor synthesis.
Dosificación por especie
- Adjunctive therapy of acute liver failure · 1-5 mg/kg PO or SC q24h · PO, SC · q24h
- Anticoagulant rodenticide toxicity (exposed but non-bleeding) · 1.25-2.5 mg/kg PO twice daily with a fatty meal · PO · q12h · 2-4 weeks
- Anticoagulant rodenticide toxicity (bleeding patient) · 2.5 mg/kg PO twice daily with a fatty meal · PO · q12h · minimum of 4 weeks
- Anticoagulant rodenticide toxicity (symptomatic) · Loading dose of 2.5-5 mg/kg PO, then 3-5 mg/kg PO divided twice daily · PO · q12h · 14 days (1st gen) or at least 30 days (2nd gen/unknown)
- Known 1st generation coumarin toxicity or vitamin K1 deficiency · initially 2.5 mg/kg s.c. in several sites, then 1-2.5 mg/kg in divided doses p.o. · SC/PO · q8-12h · 5-7 days · Administer SC initially, followed by oral maintenance.
- Known 2nd generation coumarin (brodifacoum) toxicity · initially 5 mg/kg s.c. in several sites, then 2.5 mg/kg p.o. · SC/PO · q12h · 3 weeks · Restrict activity for 1 week post-treatment. Re-evaluate coagulation status 3 weeks after cessation of treatment.
- Known inandione (diphacinone) or unknown anticoagulant toxicity · initially 2.5-5 mg/kg s.c. over several sites. Then 2.5 mg/kg p.o. divided · SC/PO · q8-12h · 3-4 weeks · Re-evaluate coagulation status 2 days after stopping therapy. If PT is elevated, continue therapy for 2 additional weeks. If normal, rest for 1 week.
- Liver disease (pre-biopsy) · 0.5-1.0 mg/kg · SC · q12h · 1-2 days · Re-evaluate coagulation time before biopsy. If minimal improvement, fresh frozen plasma may be required.
Vías de administración
Contraindicaciones
- Known hypersensitivity to phytonadione or its components
- Hypoprothrombinemia due to hepatocellular damage (Vitamin K cannot correct this if the liver cannot synthesize the protein precursors)
- Intravenous administration (relative contraindication due to anaphylaxis risk)
- Known hypersensitivity to phytomenadione
- Intramuscular administration in severely coagulopathic patients (risk of severe hematoma)
Efectos adversos
- Anaphylactoid reactions (especially following IV administration)
- Acute bleeding from the injection site (IM administration during early stages of treatment)
- Slow or poor absorption from SC or PO routes in hypovolemic patients
- Anaphylactic reactions (following IV administration)
- Haemolytic anaemia (in cats when overdosed)
- Anaphylaxis (primarily with IV administration)
- Injection site reactions (pain, swelling)
- Hematoma formation at injection sites (due to underlying coagulopathy)
Interacciones farmacológicas
- Oral Antibiotics · May decrease the numbers of Vitamin K-producing bacteria in the gut, though chronic therapy usually has no significant effect on phytonadione absorption.
- Mineral Oil · Concomitant oral administration may reduce the GI absorption of oral Vitamin K. · moderate
- Warfarin (and other coumarin/indanedione anticoagulants) · Phytonadione directly antagonizes the anticoagulant effects of these drugs.
- Phenylbutazone, Aspirin, Chloramphenicol, Sulfonamides, Diazoxide, Allopurinol, Cimetidine, Metronidazole, Anabolic Steroids, Erythromycin, Ketoconazole, Propranolol, Thyroid Drugs · May prolong or enhance the effects of anticoagulants, thereby antagonizing some of the therapeutic effects of phytonadione.
- Aspirin · Antagonizes the effects of vitamin K · moderate
- Chloramphenicol · Antagonizes the effects of vitamin K · moderate
- Allopurinol · Antagonizes the effects of vitamin K · moderate
- Diazoxide · Antagonizes the effects of vitamin K · moderate
- Cimetidine · Antagonizes the effects of vitamin K · moderate
- Metronidazole · Antagonizes the effects of vitamin K · moderate
- Erythromycin · Antagonizes the effects of vitamin K · moderate
- Itraconazole · Antagonizes the effects of vitamin K · moderate
Monitoreo
- Clinical efficacy (resolution or lack of hemorrhage, pale mucous membranes, weakness)
- One-stage prothrombin time (OSPT / PT)
- Proteins Induced by Vitamin K Absence (PIVKA)
- International Normalized Ratio (INR)
- Prothrombin time (PT) is the best method of monitoring therapy
- Prothrombin Time (PT) - typically normalizes within 12-24 hours of starting therapy
- Activated Partial Thromboplastin Time (aPTT)
- PIVKA (Proteins Induced by Vitamin K Absence or Antagonism)
- Clinical signs of bleeding (mucous membranes, heart rate, respiratory rate)
Sobredosis
Phytonadione is relatively non-toxic. It is highly unlikely that toxic clinical signs would result after a single overdosage. However, inappropriate routes of administration (like rapid IV injection) can cause severe anaphylactoid reactions regardless of the dose.
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