フェニトインナトリウム
**フェニトインナトリウム**は、ヒダントイン誘導体の抗けいれん薬およびクラスIB抗不整脈薬です。ヒト医療においては歴史的に重要ですが、伴侶動物における薬物動態プロファイルが好ましくないため、獣医療での使用は非常に制限されています。 - **犬**：半減期が非常に短く、急速な肝酵素の自己誘導が起こるため、頻回かつ高用量の投与を行わない限り治療血清濃度を維持することがほぼ不可能であり、長期的なてんかん管理にはほとんど使用されません。 - **猫**：半減期が著しく延長（最大108時間）し、グルクロン酸抱合経路が欠如しているため、毒性の蓄積に対して非常に敏感です。 - **臨床的適応**：現在では主に、犬や馬における**ジゴキシン誘発性心室性不整脈**の治療、または猫の特定のまれな神経筋疾患（ミオキミアや神経筋緊張症など）に限定して使用されます。 **臨床のポイント**：インスリン分泌を抑制する作用があるため、インスリノーマに続発する低血糖の補助治療として研究されてきましたが、臨床的な効果は通常わずかです。
作用機序: Phenytoin exhibits both neurological and cardiac effects through the stabilization of excitable membranes: - **Neurological**: Binds to and prolongs the inactive state of **voltage-gated sodium channels (VGSCs)** → promotes sodium efflux and limits sodium influx → stabilizes neuronal membranes and prevents the high-frequency repetitive firing necessary for seizure propagation from epileptogenic foci. - **Cardiac**: Acts as a **Class IB antiarrhythmic** (similar to lidocaine) → slightly depresses phase 0 of the cardiac action potential and shortens phase 3 repolarization → decreases overall action potential duration. It is particularly effective against digitalis-induced arrhythmias. - **Endocrine**: Inhibits the secretion of **insulin** and **vasopressin (ADH)**.
動物種別の用量
- Treatment of ventricular arrhythmias · 2-3 mg/kg · PO · q24h · Diligent monitoring is required due to accumulation risk.
- Treatment of seizures · 2-3 mg/kg daily; 20 mg/kg per week · PO · daily or weekly · Use is very controversial in this species.
- Seizures · 2.83-16.43 mg/kg · PO · q8h · To obtain serum levels from 5-10 micrograms/mL. Suggest monitoring serum levels to adjust dosage.
- Digoxin induced arrhythmias · 10-22 mg/kg · PO · q12h · Adverse effects are muscle fasciculations and sedation.
- Treatment of ventricular dysrhythmias · 20 mg/kg initially for the first 3-4 doses, followed by a maintenance dose of 10-15 mg/kg · PO · q12h · For persistent ventricular extra systoles or ventricular tachycardia where conventional treatment has failed. Suggest monitoring plasma concentrations.
- Treatment of seizures · 15-40 mg/kg · PO · three times daily
- Treatment of seizures · 20-35 mg/kg · PO · three times daily
- Treatment of seizures · 8.8-17.6 mg/kg in divided doses · PO · divided doses · Gradually increase or decrease dose to maintain control. May take several days for seizure control. Note: Unlikely to attain necessary serum levels due to fast half-life.
投与経路
禁忌
- Hypersensitivity to phenytoin or other hydantoins
- Intravenous use is contraindicated in 2nd or 3rd degree heart block
- Sinoatrial block
- Adams-Stokes syndrome
- Sinus bradycardia
有害事象
- Dogs: Anorexia, vomiting, ataxia, sedation, gingival hyperplasia, hepatotoxicity (elevated ALT, decreased albumin, hepatic lipidosis)
- Cats: Ataxia, sedation, anorexia, dermal atrophy syndrome, thrombocytopenia
- Horses: Excitement, recumbency (at high plasma concentrations)
薬物相互作用
- Chloramphenicol · Significantly increases the serum half-life of phenytoin (e.g., from 3 to 15 hours in dogs) by inhibiting its hepatic metabolism.
- Lithium · The toxicity of lithium may be enhanced.
- Meperidine · Phenytoin may decrease the analgesic properties of meperidine but enhance its toxic effects.
- Phenobarbital / Primidone · Altered pharmacologic effects; potential for additive hepatotoxicity. Weigh risks vs. benefits before combining.
- Allopurinol, Cimetidine, Diazepam, Isoniazid, Salicylates, Sulfonamides, Trimethoprim, Valproic Acid · May increase the pharmacologic effects and toxicity of phenytoin.
- Antacids, Barbiturates, Calcium, Folic Acid, Theophylline · May decrease the pharmacologic activity of phenytoin.
- Corticosteroids, Doxycycline, Estrogens, Furosemide, Quinidine · Phenytoin may decrease the pharmacologic activity of these agents via hepatic enzyme induction.
モニタリング
- Level of seizure control or arrhythmia resolution
- Signs of toxicity (sedation, ataxia)
- Body weight (monitor for anorexia)
- Liver enzymes (ALT, ALP) and serum albumin (especially with chronic therapy)
- Serum drug levels (if signs of toxicity appear or lack of efficacy is noted)
過量投与
Clinical signs of overdosage are dose-dependent: - **Lower levels**: Sedation, anorexia, and ataxia (wobbly gait). - **Higher levels**: Coma, severe hypotension, and respiratory depression. **Treatment**: Dogs rapidly clear the drug, so treatment depends on the severity of clinical signs. Severe intoxications require aggressive supportive care (IV fluids, cardiovascular and respiratory support).
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。