苯妥英鈉
**苯妥英鈉 (Phenytoin sodium)** 是一種乙內醯脲衍生物，屬於抗癲癇藥物及 IB 類抗心律不整藥物。雖然在人類醫學中具有歷史意義，但由於在伴侶動物體內的藥代動力學特徵不佳，其在獸醫學中的應用受到高度限制。 - **犬**：極少用於長期癲癇管理，因為其半衰期極短且會快速誘發肝臟酵素（自我誘導），導致除非頻繁且高劑量給藥，否則幾乎無法維持治療血清濃度。 - **貓**：由於半衰期嚴重延長（高達 108 小時）且缺乏葡萄糖醛酸結合途徑，極易產生毒性蓄積。 - **臨床定位**：目前主要保留用於治療犬和馬的**毛地黃誘發之心室心律不整**，或貓的特定罕見神經肌肉疾病（如肌纖維顫搐和神經性肌強直）。 **臨床提示**：由於其具有抑制胰島素分泌的能力，曾被研究作為胰島素瘤繼發低血糖的輔助治療，但臨床效益通常微乎其微。
作用機制: 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)**.
各物種劑量
- 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.
給藥途徑
禁忌症
- Hypersensitivity to phenytoin or other hydantoins
- Intravenous use is contraindicated in 2nd or 3rd degree heart block
- Sinoatrial block
- Adams-Stokes syndrome
- Sinus bradycardia
不良反應
- 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)
藥物相互作用
- 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.
監測
- 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
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 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。