Phenytoin
Phenytoin is a hydantoin-derivative anticonvulsant and Class IB antiarrhythmic agent. **Clinical Pearl:** While historically used for epilepsy in veterinary medicine, its use in dogs has largely been abandoned due to a very short half-life (requiring frequent dosing) and a high risk of hepatotoxicity. It has been superseded by safer and more effective alternatives like phenobarbital, levetiracetam, and zonisamide. > **Warning:** Phenytoin is highly toxic to cats due to their deficient hepatic glucuronidation pathways, leading to severe accumulation and toxicity even at very low doses.
Mecanismo: Diminishes the spread of focal neural discharges by promoting sodium efflux from neurons via the **voltage-gated sodium channels** → stabilizes the neuronal membrane → raises the threshold against hyperexcitability. It also acts on Purkinje fibers in the heart to shorten the action potential duration, functioning as a Class IB antiarrhythmic.
Vías de administración
Contraindicaciones
- Cats (due to severe toxicity)
- Hepatic dysfunction
- Bradycardia
- High-grade AV block
Efectos adversos
- Hepatotoxicity (especially in dogs)
- Ataxia
- Sedation
- Gingival hyperplasia
- Peripheral neuropathy
- Hypotension and arrhythmias (with rapid IV administration)
Interacciones farmacológicas
- Phenobarbital · Unpredictable effects on serum concentrations of both drugs due to CYP450 induction · moderate
- Chloramphenicol · Inhibits hepatic metabolism of phenytoin, leading to increased levels and toxicity · major
- Cimetidine · Inhibits metabolism of phenytoin, increasing risk of toxicity · moderate
- Corticosteroids · Phenytoin induces hepatic enzymes, increasing the clearance and reducing the efficacy of corticosteroids · moderate
Monitorización
- Serum drug concentrations (therapeutic range typically 10-20 mcg/mL, though rarely monitored now due to infrequent use)
- Liver enzymes (ALT, AST, ALP) and bilirubin
- ECG and blood pressure during IV administration
Sobredosis
Clinical signs of overdose include severe ataxia, tremors, lethargy, vomiting, and paradoxical seizures. Rapid IV overdose leads to hypotension and cardiac arrest. **Treatment:** Consists of supportive care, IV fluid therapy, and cardiovascular monitoring. There is no specific antidote.
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