Primidone
Primidone is a barbiturate-derivative anticonvulsant that acts primarily as a prodrug, being rapidly converted into **phenobarbital** and **phenylethylmalonamide (PEMA)** in dogs. While historically used for seizure control (idiopathic epilepsy, epileptiform convulsions) in dogs, **most veterinary neurologists no longer recommend its use as a first-line agent**. > **Clinical Pearl:** The increased incidence of severe hepatotoxicity associated with primidone compared to phenobarbital is the major limiting factor for long-term therapy. In dogs, the conversion rate of primidone to phenobarbital is approximately 4:1 (a 250 mg dose of primidone is roughly equivalent to 60 mg of phenobarbital). Some clinicians reserve primidone for refractory cases where phenobarbital alone is insufficient, theorizing that the PEMA metabolite may potentiate phenobarbital's anticonvulsant activity. It is considered highly toxic to cats and rabbits.
Mecanismo: Primidone and its active metabolites, **phenylethylmalonamide (PEMA)** and **phenobarbital**, exert anticonvulsant effects by raising seizure thresholds and altering seizure patterns. **Mechanistic Pathway:** * **Phenobarbital (Primary active metabolite):** Binds to the allosteric barbiturate site on **GABA_A receptors** in the CNS → prolongs the duration of chloride channel opening → increases intracellular chloride influx → hyperpolarizes the postsynaptic neuron → globally depresses CNS excitability and raises the seizure threshold. * **PEMA:** Has weak intrinsic anticonvulsant activity but is believed to synergistically potentiate the effects of phenobarbital. * **Primidone (Parent drug):** May have some independent action on voltage-gated sodium channels, though its primary efficacy in veterinary species is attributed to its phenobarbital metabolite.
Dosificación por especie
- Seizure control · 20 mg/kg · PO · q12h · Extreme caution advised; many consider contraindicated in cats.
- Seizure control · 10-30 mg/kg per day divided into 2-3 doses · PO · divided into 2-3 doses · Initially
- Seizure control · 10 mg/kg · PO · q8h · Not recommended as first choice
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Severe liver disease
- Demonstrated previous hypersensitivity to primidone or barbiturates
- Nephritis (large doses contraindicated)
- Severe respiratory dysfunction (large doses contraindicated)
- Cats (considered contraindicated by many clinicians due to high toxicity risk)
Efectos adversos
- Anxiety and agitation (especially during initiation)
- Elevated liver enzymes (ALT, ALP, GLDH)
- Decreased serum albumin
- Hepatic lipidosis
- Hepatocellular hypertrophy and necrosis
- Extramedullary hematopoiesis
- Depression and sedation
- Ataxia
- Polydipsia (PD)
- Polyuria (PU)
- Polyphagia
- Anorexia
- Tachycardia
- Dermatitis
- Episodic hyperventilation
- Urolith formation (primidone uroliths reported)
Interacciones farmacológicas
- Acetaminophen · Increased risk for hepatotoxicity, particularly with large or chronic doses of barbiturates.
- Carbonic Anhydrase Inhibitors (e.g., acetazolamide) · Oral administration may decrease the GI absorption of primidone.
- Monoamine Oxidase Inhibitors (e.g., amitraz, selegiline) · May prolong phenobarbital effects.
- Phenytoin · Barbiturates may affect phenytoin metabolism, and phenytoin may alter barbiturate levels; therapeutic monitoring indicated.
- Rifampin · May induce enzymes that increase the metabolism of barbiturates.
- Antihistamines · May increase the CNS depressant effects of phenobarbital.
- Chloramphenicol · May increase the effects of phenobarbital; phenobarbital may also decrease chloramphenicol levels.
- Opiates · May increase the CNS depressant effects of phenobarbital.
- Phenothiazines · May increase the effects of phenobarbital; phenobarbital may decrease phenothiazine serum concentrations.
- Valproic Acid · May increase the effects of phenobarbital.
- Warfarin · Phenobarbital may decrease anticoagulant effects by lowering serum concentrations.
- Beta-blockers · Phenobarbital may decrease effects by lowering serum concentrations.
Monitoreo
- Anticonvulsant efficacy (seizure frequency and severity)
- Adverse effects (CNS depression, PU/PD, weight gain, signs of liver disease)
- Serum phenobarbital levels (therapeutic range in dogs thought to be 15-40 mcg/mL) if lack of efficacy or adverse reactions are noted
- Routine CBCs and liver enzyme panels at least every 6 months during chronic therapy
Sobredosis
**Clinical Signs:** Because primidone is rapidly metabolized to phenobarbital in dogs, signs of acute toxicity mirror barbiturate overdose: sedation progressing to coma, anorexia, vomiting, ataxia, and nystagmus. **Treatment:** * **Decontamination:** Removal of ingested product from the gut if appropriate (emesis or gastric lavage). * **Adsorbents:** **Activated charcoal** is of considerable benefit in enhancing the clearance of phenobarbital (acts as a 'sink' for the drug to diffuse from the vasculature back into the gut), even if the drug was administered parenterally. * **Supportive Care:** Provide respiratory and cardiovascular support. * **Enhanced Elimination:** Forced alkaline diuresis can augment elimination in patients with normal renal function. Peritoneal dialysis or hemodialysis may be helpful in severe intoxications or anuric patients.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.