title: Effects of chloramphenicol, cimetidine and phenobarbital on and tolerance to xylazine-ketamine anesthesia in dogs.
abstract: The effects of chloramphenicol, cimetidine and phenobarbital on the xylazine-ketamine anesthesia and the development of tolerance to xylazine-ketamine and xylazine were studied in dogs. The duration of absence of pedal reflex, duration of return of consciousness, and duration for return of ambulation were determined. Pretreatment with chloramphenicol (33 mg/kg, iv, 15 min) and cimetidine (5 mg/kg, iv, 24 h) did not influence any of the above parameters significantly. Phenobarbital pretreatment (15 mg/kg, iv, 96 h) significantly reduced the duration of anesthesia. Although not significant, there is a trend toward the development of tolerance to repeated administration of xylazine (1.1 mg/kg, iv) and ketamine (10 mg/kg, iv) combination and xylazine (1/1 mg/kg, iv) alone once daily at 3 d intervals for 9 d. These results indicate that hepatic cytochrome P-450 drug metabolizing enzymes, inhibited by chloramphenicol and cimetidine, might not be involved in the metabolism of xylazine and/or ketamine, phenobarbital inducible hepatic cytochrome P-450 enzymes might play a role in metabolic disposition of xylazine and/or ketamine, and repeated administration of xylazine alone or in combination with ketamine might lead to development of tolerance in dogs.
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078-0353.
authors.forename: B C
authors.initials: BC
authors.lastname: Nossaman
authors.forename: H R
authors.initials: HR
authors.lastname: Amouzadeh
authors.forename: S
authors.initials: S
authors.lastname: Sangiah
mesh_terms: D000758:Anesthesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002701:Chloramphenicol / Q000008:administration & dosage / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D003243:Consciousness / Q000187:drug effects; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004361:Drug Tolerance; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects; D013843:Thiazines / Q000494:pharmacology*; D014991:Xylazine / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D013843:Thiazines; D014991:Xylazine; D002701:Chloramphenicol; D007649:Ketamine; D002927:Cimetidine; D010634:Phenobarbital