Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).
The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.
Dayrell-Hart
B
B
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6010.
Steinberg
S A
SA
VanWinkle
T J
TJ
Farnbach
G C
GC
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004283:Dog Diseases / Q000139:chemically induced*; D004285:Dogs; D005260:Female; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000662:veterinary*; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy / Q000662:veterinary*
D010634:Phenobarbital