피토나디온 (비타민 K1)

해독제, 지용성 비타민

**피토나디온(비타민 K1)**은 천연 비타민 K1과 동일한 합성 지용성 비타민입니다. 수의학에서 매우 중요한 해독제로, 주로 **항응고성 살서제**(예: 와파린, 브로디파쿰, 브로마디올론) 섭취로 인한 응고 장애를 역전시키는 데 사용됩니다. 주요 임상 적용: * **항응고성 살서제 중독:** 치료의 핵심입니다. 2세대 살서제는 반감기가 매우 길어 종종 3~4주간의 지속적인 비타민 K1 보충이 필요합니다. * **스위트 클로버 중독:** 반추동물에서 곰팡이가 핀 스위트 클로버로 인한 디쿠마롤 중독을 치료하는 데 사용됩니다. * **간 질환:** 비타민 K의 흡수나 이용이 손상된 급성 간부전 또는 담도 폐쇄 시 보조 요법으로 사용됩니다. * **설파퀴녹살린 중독:** 이 항콕시듐제와 관련된 출혈성 질환을 역전시킵니다. > **임상 요점:** 비타민 K1(피토나디온)은 이러한 중독에 효과적이지만, 비타민 K3(메나디온)는 효과가 없고 독성 위험이 더 높습니다. 피토나디온이 새로운 응고 인자를 합성하는 데는 6~12시간이 걸립니다. 따라서 활동성 출혈이 있는 환자는 활성 응고 인자를 공급하기 위해 즉각적인 혈장 또는 전혈 수혈이 필요합니다.

작용 기전: 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.

동물 종별 용량

Cats

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.

Swine

투여 경로

POSCIMIV (Not recommended/Extreme caution)

금기

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)

이상반응

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)

약물 상호작용

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

모니터링

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)

과용량

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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