Page 796 - Clinical Small Animal Internal Medicine

764 Section 8 Neurologic Disease

bioavailability, being rapidly absorbed within two hours samples are best taken in the early morning, prior to dos-
VetBooks.ir and with a maximal plasma concentration obtained ing, in a fasted dog, to increase consistency in compari-
son with published information, maintain consistency in
within 4–8 hours following oral administration. Almost
one‐half of the drug is protein bound. The majority of
fluctuations of absorption.
phenobarbital is metabolized by the liver, with approxi- interpretation, and remove diurnal or dietary‐induced
mately one‐third excreted unchanged in the urine. Adjustments in AED dosages are undertaken either to
Phenobarbital is an autoinducer of hepatic microsomal enhance the effect or to reduce the adverse effects. The
enzymes (P450 system), which can progressively reduce most efficacious and safe trough therapeutic phenobar-
the elimination half‐life with chronic dosing. bital range is 15–30 μg/mL. An optimal starting level is
between 20 and 25 μg/mL. Increments of 5 μg/mL are
Adverse Effects Overall, phenobarbital is well tolerated beneficial if seizures are occurring at an equal frequency
at therapeutic serum concentrations in the dog and cat. or worsening after 30 days of therapy. Cats in general can
Idiosyncratic drug reactions to phenobarbital can be tolerate higher serum levels in the 30–45 range without
either behavioral or biochemically mediated. A more complications.
serious idiosyncratic reaction is development of an Adjustments of the trough phenobarbital levels can be
immune‐mediated neutropenia or thrombocytopenia in calculated with the following formula:
dogs, as well as anemia. Rare acute, idiosyncratic hepato-
toxic reactions may also be present, as evidenced by a Desired concentrationActual concentration
/
rapid elevation of alanine aminotransferase (ALT) and total mg PB perdaay Oral daily dose of PB mg
abnormal dynamic bile acid levels. The drug should be
stopped immediately if either neutropenia or dramatic Potassium Bromide
elevations in ALT are noted and replaced with a nonhe- Potassium bromide can be used as either monotherapy
patic metabolized AED. or as an add‐on AED of choice in the dog. Concomitant
The most serious and potentially life‐threatening com- potassium bromide and phenobarbital administration
plications that can occur with long‐term phenobarbital decreased seizure number and severity in the majority of
therapy are hepatotoxicity and development of superfi- dogs in several studies, with seizure‐free status ranging
cial necrolytic dermatitis in dogs. Documentation of a from 21% to 72% of all treated dogs. In general, many
serum phenobarbital concentration >35 μg/mL had the canine refractory idiopathic epileptic patients may ben-
highest correlation with the development of hepatotox- efit from potassium bromide. By allowing a reduction in
icity. All animals on chronic phenobarbital therapy the use of drugs metabolized by the liver, potassium
should have a routine biochemistry panel performed bromide therapy may also reduce the incidence of hepa-
every 6–12 months to monitor for the development of totoxicity. Bromide is not recommended for use in cats
chronic hepatotoxicity. A bile acid tolerance test should due to potential for life‐threatening allergic asthmatic
be performed to evaluate liver function if ALT levels sud- reaction.
denly increase or if the serum albumin level starts to
decrease. Hepatotoxicity is uncommon to occur in cats.
Pharmacology A starting dose of 40 mg/kg/day potas-
Dosage and Monitoring The appropriate starting dose of sium bromide is slowly metabolized in the dog, with a
phenobarbital is 2.5 mg/kg orally q12h in dogs and 2.5 median elimination half‐life of 15.2 days, Steady‐state
mg/kg q24h in cats. An intravenous loading dose can be concentrations fluctuate between dogs, most likely due
used to produce a rapid rise in serum blood concentra- to individual differences in clearance and bioavailability.
tion. This starting dose is the only time a weight‐based Dietary factors also alter serum drug concentrations,
dosage is used. All future adjustments should be based with high‐chloride diets resulting in excessive renal
on serum drug concentrations in conjunction with clinical secretion and lower serum concentrations.
assessment.
The goal of drug level monitoring is to be proactive Adverse Effects Potassium bromide is generally well tol-
rather than reactive in seizure prophylaxis. Serial serum erated in the dog. The most common adverse effects
trough phenobarbital concentrations should be evalu- seen with potassium bromide and phenobarbital combi-
ated at 14, 60,180, and 360 days after the initiation of nation therapy are polydipsia, polyphagia, increased
treatment, at six‐month intervals thereafter, if the pet lethargy, and mild ataxia with increasing serum concen-
has more than two seizure events between these time tration. Pancreatitis and gastrointestinal intolerance
points, and at two weeks after a dosage change. Although have also been reported. Chronic use at higher serum
blood level fluctuations may not be dramatic throughout concentations can result in pelvic limb ataxia and excess
the day in dogs with steady‐state concentrations, blood sedation.