Page 1132 - Small Animal Internal Medicine, 6th Edition

1104 PART IX Nervous System and Neuromuscular Disorders

absorbed and renally excreted, with some hepatic metabo- be a problem in cats. Diazepam is eliminated by hepatic
lism. The elimination half-life in dogs is very short (3-4 metabolism, and the only common adverse effect is sedation,
VetBooks.ir hours), requiring dosing every 6 to 8 hours. Gabapentin although idiosyncratic severe, life-threatening hepatotoxic-
ity has been documented in a few cats receiving daily oral
improves seizure control in more than 50% of dogs when
added to PB or KBr. Starting doses of 10 to 20 mg/kg q8h
warrants close owner observation of appetite and attitude
have been recommended in dogs, but the dose can be diazepam for 5 to 11 days. This potentially fatal reaction
increased gradually as needed (up to 80 mg/kg q8h) as long and periodic monitoring of liver enzymes in all cats treated
as excessive sedation does not occur, which is the only with oral diazepam. PB is a better choice for chronic AED
reported adverse effect. Serum concentrations are rarely therapy in cats.
monitored, but the suspected therapeutic range for dogs is 4 Diazepam also has a place in the emergency management
to 16 mg/L. An oral dose of 5 to 10 mg/kg every 8 to 12 of seizures and in the at-home treatment of dogs with IE
hours has been recommended and used with limited success experiencing cluster seizures. In dogs with a recognizable
in cats. preictal phase or an aura preceding the seizure, an injectable
preparation of diazepam (5 mg/mL) can be administered
FELBAMATE rectally (2 mg/kg) by the owner at the onset of these pre-
Felbamate (Felbatol [Wallace]) can be an effective AED in monitory signs. Alternatively, this dose can be administered
dogs when used alone or as an add-on drug in dogs refrac- just after each observed seizure, with a maximum of three
tory to AED therapy with PB and KBr. After urinary excre- doses in 24 hours (each dose separated by at least 10 minutes).
tion of 70% of the orally administered dose, felbamate is At-home rectal administration of diazepam decreases the
metabolized by hepatic microsomal P450 enzymes. The rec- occurrence of cluster seizures and the development of status
ommended starting dose is 15 mg/kg q8h. Felbamate appears epilepticus as well as dramatically decreasing the need for
to have a wide margin of safety, and the daily dose can be owners to seek expensive emergency treatment for their epi-
increased in 15-mg/kg increments until the seizures are leptic dogs. Diazepam dispensed for at-home rectal admin-
adequately controlled, with reports of dosages as high as istration should be stored in a glass vial because plastic will
70 mg/kg q8h without significant toxicity. Trough serum adsorb the drug, decreasing its effectiveness. For administra-
concentrations between 25 and 100 mg/L may be therapeu- tion, the drug can be drawn into a syringe and injected
tic, but the target range is not well established in dogs. Fel- through a 1-inch plastic teat cannula or rubber catheter
bamate is an unusual AED in that it does not cause sedation. directly into the rectum.
Potential side effects include nervousness and keratocon-
junctivitis sicca. Mild reversible thrombocytopenia and leu-
kopenia have also been reported. The potential for aplastic ALTERNATIVE THERAPIES
anemia and fatal hepatopathy has limited the use of felba-
mate in human patients, but anemia has not been reported Approximately 20% to 25% of dogs treated for epilepsy using
in dogs. Approximately 30% of dogs treated with felbamate standard AED therapy are never well controlled, despite
as an add-on drug with PB do develop hepatotoxicity, attempts at therapeutic drug monitoring and appropriate
however, so monitoring of CBCs, biochemistry panels, and dose adjustments. It is important to evaluate poorly con-
liver function tests is recommended every 3 months during trolled animals for underlying metabolic or intracranial
treatment. disease that could be specifically treated. Alternative treat-
ments should also be considered in these animals, including
PREGABALIN hypoallergenic diets, acupuncture, surgical division of the
Pregabalin (Lyrica [Pfizer]) is a structural analog of GABA. corpus callosum, and vagus nerve stimulation.
The mean elimination half-life in dogs is approximately 7
hours. This AED is renally excreted and has few drug inter-
actions. Efficacy as an add-on AED has been promising in EMERGENCY THERAPY FOR DOGS AND
dogs. The initial recommended dose is 4 mg/kg orally every CATS IN STATUS EPILEPTICUS
8 to 12 hours. Adverse effects are limited to sedation and
ataxia. Status epilepticus is a series of seizures or continuous seizure
activity lasting for 5 minutes or longer without periods of
DIAZEPAM intervening consciousness. Status epilepticus increases arte-
Diazepam (Valium [Roche]) is of limited use as a chronic rial blood pressure, body temperature, heart rate, cerebral
oral AED in dogs because of its expense, its very short half- blood flow, and cerebral oxygen consumption. It also
life, physical dependence, and the rapid development of decreases blood pH (because of lactic acidosis) and may
tolerance to its anticonvulsant effects. Oral diazepam decrease effective ventilation. As seizures continue, meta-
(0.5-2.0 mg/kg q8-12h) has been shown to be of some benefit bolic deterioration, increased intracranial pressure, acidosis,
for the long-term management of seizures in cats because it hyperthermia, and cardiac dysrhythmias are common,
has a long elimination half-life in that species and a func- leading to progressive cerebral ischemia and neuronal death.
tional tolerance to its anticonvulsant effect does not seem to Permanent neurologic damage can result, and mortality rates