植甲萘醌 (維生素K1)
**植甲萘醌 (維生素K1)** 是一種合成的脂溶性維生素，與天然存在的維生素K1相同。它是獸醫學中關鍵的解毒劑，主要用於逆轉因攝入**抗凝血殺鼠劑**（如華法林、溴鼠隆等）引起的凝血障礙。 主要臨床應用包括： * **抗凝血殺鼠劑中毒：** 治療的核心。第二代殺鼠劑半衰期極長，通常需要連續補充維生素K1長達3-4週。 * **甜苜蓿中毒：** 用於反芻動物，治療因發霉甜苜蓿引起的雙香豆素中毒。 * **肝臟疾病：** 作為急性肝衰竭或膽道阻塞（影響維生素K吸收或利用）的輔助治療。 * **磺胺喹噁啉中毒：** 逆轉與此抗球蟲藥相關的出血性疾病。 > **臨床要點：** 維生素K1 (植甲萘醌) 對這些中毒有效，而維生素K3 (甲萘醌) 無效且具有較高的毒性風險。植甲萘醌需要6-12小時才能合成新的凝血因子；因此，對於正在出血的病患，必須立即輸注血漿或全血以提供活性凝血因子。
作用機制: 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.
各物種劑量
- 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.
給藥途徑
禁忌症
- 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)
不良反應
- 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)
藥物相互作用
- 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
監測
- 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)
過量
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.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。