Phenytoin Sodium
**Phenytoin sodium** is a hydantoin-derivative anticonvulsant and Class IB antiarrhythmic agent. While historically significant in human medicine, its use in veterinary medicine is highly restricted due to unfavorable pharmacokinetic profiles in companion animals. - **Dogs**: Rarely used for long-term epilepsy management because of a very short half-life and rapid hepatic autoinduction, which makes maintaining therapeutic serum levels nearly impossible without frequent, high-dose administration. - **Cats**: Highly susceptible to toxic accumulation due to a severely prolonged half-life (up to 108 hours) and deficient glucuronidation pathways. - **Clinical Niche**: Today, it is primarily reserved for treating **digoxin-induced ventricular arrhythmias** in dogs and horses, or specific rare neuromuscular conditions (e.g., myokemia and neuromyotonia in cats). **Clinical Pearl**: Because of its ability to inhibit insulin secretion, it has been investigated as an adjunctive treatment for hypoglycemia secondary to insulinomas, though clinical benefits are often minimal.
Mecanismo: 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)**.
Dosificación por especie
- 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.
Vías de administración
Contraindicaciones
- Hypersensitivity to phenytoin or other hydantoins
- Intravenous use is contraindicated in 2nd or 3rd degree heart block
- Sinoatrial block
- Adams-Stokes syndrome
- Sinus bradycardia
Efectos adversos
- 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)
Interacciones farmacológicas
- 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.
Monitorización
- 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)
Sobredosis
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).
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