TABLE 22-3.

Anticonvulsant Drugs Available for Use in Dogs and Cats

DRUG	USE AND MECHANISM OF ACTION	PHARMACOLOGY	DOSAGES	SIDE EFFECTS AND CAUTIONS
Diazepam	Prolongs opening of GABA receptors; used for short- term control of seizures; drug of choice for emergency treatment of status epilepticus/cluster seizures; can be used for long-term management in cats	Metabolized in liver, excreted by kidneys (90%) and in feces (10%) Bioavailability: 80% t1/2 (dogs): 3 hours t1/2 (cats): 5 hours t1/2 of active metabolite nordiazepam in cats = 21-hour maximum CNS concentration reached 1 minute after IV administration	Dogs, cats: 0.5-2 mg/kg IV, rectally CRI: 0.5-2 mg/kg/hr IV in 0.9% NaCl Cats: 0.5-2 mg/kg PO BID for long-term use	Sedation CRI can cause apnea Dogs develop tolerance Acute fulminant hepatic necrosis in cats (idiosyncratic) Used cautiously in animals with liver dysfunction
Midazolam	Prolongs opening of GABA receptors; used for short- term control of seizures; drug of choice for emergency treatment of seizures	Metabolized in liver, excreted by kidneys (>90%) and in feces (<10%) Bioavailability: 90% t1/2 (dogs): 77 minutes	Dogs: 0.07-0.22 mg/kg IV, IM, intranasally, rectally CRI: 0.5-2 mg/kg/hr IV	Sedation CRI can cause apnea Used cautiously in animals with liver dysfunction No data for cats
Propofol	Effects GABA receptor ionophor complex; used for short-term control of seizures; drug of choice for emergency treatment of seizures not controlled with benzodiazepines; used for hepatopathy- induced seizures	Metabolized via extrahepatic routes; rapidly distributed to whole body; effects seen within 1 minute; anesthesia lasts 5 minutes after single bolus	Dogs, cats: 4-8 mg/kg IV to effect CRI: 0.1-0.6 mg/kg/min IV	Induces anesthesia (intubation necessary) Apnea and hypoxemia Myocardial depression
Phenobarbital	Increases neuronal response to GABA; prevents glutamate-induced postsypnatic decrease in neuronal calcium influx; used for generalize seizures	Metabolized in liver Bioavailability: 90% t1/2 (dogs): 24-40 hours Tss: 10-14 days	Dogs, cats: 2-5 mg/kg PO BID	Transient: ataxia, lethargy, behavioral changes Persistent: PU/PD polyphagia, obesity, lethargy, splenomegaly, hepatomegaly, increased ALT and ALP, decreased serum thyroxine Severe side effects: hepatotoxicity, myelofibrosis, necrotizing superficial dermatitis
Potassium bromide	Hyperpolarization of neuronal membranes through chloride channels; used for generalized seizures	Excreted unmetabolized by kidneys Bioavailability: 60% t1/2 (dogs): 25 days t1/2 (cats): 10 days Tss (dogs): 90-120 days Tss (cats): 50 days	Dogs, cats: 30-60 mg/kg PO SID	Transient: ataxia, sedation, hyperactivity, vomiting Persistent: PU/PD Rare: aggression, dermatitis, pancreatitis Increased risk of asthma in cats; impaired renal function elevates blood levels; high salt diet increases bromide secretion
Felbamate	Inhibition of NMDA receptors; potentiation of GABA receptors; used for partial seizures; added to phenobarbital and potassium bromide	Metabolized in liver (30%), excreted by kidneys (70%) Bioavailability: 85% t1/2: 5-6 hours Tss: 24-30 hours	Dogs: 15-70 mg/kg PO BID-TID, increased in 15-mg/kg increments up to 70 mg/kg/day PO	Rare: nervousness, hyperexcitability, liver toxicity, bone marrow suppression No data for cats
Gabapentin	Mechanism of action not completely understood; may enhance effects of phenobarbital, diazepam, felbamate; added to phenobarbital and potassium bromide; also used for neurogenic pain management	Minimally metabolized in liver, excreted by kidneys Bioavailability: 80% t1/2: 3-4 hours	Dogs: 25-60 mg/kg PO BID-TID	Rare: sedation Questionable efficacy in dogs, owing to short t1/2 Can be used in cats, but no data available
Levetiracetam	Mechanism of action unknown; added to phenobarbital and potassium bromide; potentially a monodrug therapy; used for generalized seizures and hepatopathy-related seizures	Excreted unchanged or hydrolyzed by kidneys Bioavailability: ≈100% t1/2: 4 hours Anticonvulsant effects last longer despite short t1/2	Dogs: 25-60 mg/kg PO BID-TID	Rare: salivation, restlessness, vomiting, ataxia
Zonisamide	Blocks voltage-dependent sodium channels and t-type calcium channels; enhances dopaminergic and serotonergic neurotransmission; inhibits glutamate- induced excitation; added to phenobarbital and potassium bromide; used for generalized seizures	Metabolized in liver Bioavailability: 80% t1/2: 15 hours Tss: 3 days	Dogs: 10 mg/kg PO BID	Rare: drowsiness, ataxia, gastrointestinal upset

GABA, Gamma-aminobutyric acid; t_1/2, half-life time; CNS, central nervous system; CRI, constant rate infustion; Tss, time-to-steady rate; PU/PD, polyuria/polydipsia;

ALT, alanine aminotransferase; ALP, alkaline phosphatase.

NMDA, N-methyl-d-aspartic acid.