Phenobarbitone
enhances GABA activity (by binding to a barbiturate receptor
on chloride channel complex). This results in higher intracellular
concentrations of chloride and hyperpolarisation of the resting
membrane potential (increasing the threshold for seizure discharge).
The initial elimination half-life of phenobarbitone after oral
administration is 37 to 89 hours in dogs. However this is significantly
decreased with time as a result of increased total body clearance.
It takes 12 to 15 days to reach steady state concentration of
phenobarbitone in dogs. Phenobarbitone is primarily metabolised
in the liver and causes induction of liver enzymes.
Indications
Drug of first choice in management of canine epilepsy.
Dose
In dogs, phenobarbitone can be started at 3 mg/kg twice daily orally. Oral
doses are adjusted based on serum levels and seizure frequency. Recommended therapeutic
range in dogs is 20 to 35 ug/ml.
Side
effects
Common side effects include polyuria, polydipsia, polyphagia, transient sedation
or hyperexcitability and ataxia. These are common one to two weeks after the
onset of the treatment or after increasing the oral dosage but usually resolve
as tolerance develops. Polyuria, polyphagia and polydipsia are the most common
long-term side effects. Other side effects include haematological abnormalities
such as neutropenia, anaemia and thrombocytopenia.
Hepatotoxicity
is rare (mostly seen in dogs on chronic treatment with phenobarbitone
serum level above 35 mg/L) and is characterised by sedation,
ataxia, anorexia, icterus, ascites or coagulopathy with increased
pre- and post-prandial serum bile acids, low albumin, increased
ALT, ALP, bilirubin. An increase in liver enzyme concentration
is to be expected in all animals receiving phenobarbitone and
so liver function tests are required to monitor the effects on
the liver. Hepatotoxicity may be reversible if detected early
and phenobarbitone withdrawn. There is an increased risk of pancreatitis
in dogs receiving both bromide and phenobarbitone.
| • |
Phenobarbitone
treatment does not affect adrenal function tests (ACTH stimulation
test and low dose dexamethasone test) despite acceleration in
dexamethasone metabolism. |
| • |
Phenobarbitone treatment significantly decreases total T4 and free T4
concentration. TSH only shows a compensatory increase while total T3 has minimal
fluctuation and cholesterol increases toward the upper limits of the normal range. |
 |
Epiphen
datasheet
tablets and solution |
ver.060104 |
|
Fact Sheet Phenobarbitone |
ver.100308 |
References
Chauvet
AE, Feldman EC, Kass PH (1995) Effects of phenobarbital
administration on results of serum biochemical analyses and adrenocortical
function test in epileptic dogs. JAVMA 207,1305-1307.
- PubMed -
Dayrell-Hart
B, Steinberg SA, Van winkle et al (1991) Hepatotoxicity
of phenobarbital in dogs: 18 cases (1985-1989). JAVMA 199,
1060-1066. - PubMed–
Dyer
KR, Shell LG (1993) Anticonvulsant therapy: a practical
guide to medical management of epilepsy in pets. Vet
Med 88, 647-653.
Gieger
TL, Hosgood G, Taboada J et al (2000) Thyroid function
and serum hepatic enzyme activity in dogs after phenobarbital
administration. JVIM 14,
277-281. - PubMed -
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