A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pattern with an alpha-phase distribution half-life of < 3 minutes. The beta-phase half-life was in the range of 50 to 150 minutes. The CNS effects peaked at 20 minutes after administration, and the hemodynamic effects peaked at 100 minutes. In all horses, the most sensitive variable was the PCV, which decreased by up to 20% (P < 0.0001). Systolic, diastolic, and mean blood pressures decreased (P < 0.0001); heart rate was unchanged (P > 0.05). Neither blood gas tensions nor blood pH changed noticeably (P > 0.05). In all horses studied, acepromazine had a significant (P < 0.0001) sedative effect, as observed by posture and alertness. None of the observed pharmacodynamic effects correlated well with plasma acepromazine concentration. These effects persisted beyond the time of detectable acepromazine concentration, indicating that they might be caused by active metabolites, or that their timing could result from complex pharmacokinetic compartment influences.

Plasma catecholamine concentrations in response to onychectomy were examined in 27 cats receiving different anesthetic regimens. Each cat was anesthetized with a dissociative-tranquilizer combination, and onychectomy was performed on 1 forefoot. One week later, each cat was anesthetized with the same dissociative-tranquilizer combination plus either butorphanol or oxymorphone, and onychectomy was performed on the other forefoot. Four treatment groups were studied: tiletamine-zolazepam and tiletamine-zolazepam-butorphanol combinations were administered to group-1 cats, ketamine-acepromazine and ketamine-acepromazine-butorphanol combinations were administered to group-2 cats, tiletamine-zolazepam and tiletamine-zolazepam-oxymorphone combinations were administered to group-3 cats, and ketamine-acepromazine and ketamine-acepromazine-oxymorphone combinations were administered to group-4 cats. All drug combinations were administered IM. Central venous blood samples were drawn for catecholamine analysis after injection of drug(s), after onychectomy, and 1, 2, and 4 hours after injection. Tiletamine-zolazepam alone or tiletamine-zolazepam-butorphanol prevented epinephrine release for 2 hours after injection of drug(s). Norepinephrine concentration increased significantly (P < 0.05) from baseline after onychectomy for tiletimine-zolazepam-butorphanol and at 4 hours for tiletamine-zolazepam and tiletamine-zolazepambutorphanol. After onychectomy, there was no difference in epinephrine values between tfletamine-zolazepam and tiletamine-zolazepam-oxymorphone. Ketamine-acepromazine prevented increases in norepinephrine and epinephrine concentrations for up to 2 hours after surgery. Addition of butorphanol to ketamine-acepromazine decreased norepinephrine values immediately after onychectomy. Addition of oxymorphone to ketamine-acepromazine resulted in lower epinephrine values 4 hours after surgery.

Effects of 2 drugs commonly used for chemical restraint of cattle were evaluated for their effect on laryngeal and pharyngeal anatomy, function, and response to stimuli. Eighteen adult Jersey cows, free of respiratory tract disease, were studied. Cows were assigned at random to 1 of 3 treatment groups. Endoscopic evaluations were performed before and at a predetermined time interval after administration of each drug. Responses to stimuli were evaluated by stimulating 7 preselected sites (epiglottis, left and right arytenoid cartilages, left and right vocal folds, and left and right dorsolateral pharyngeal walls) with a closed, transendoscopic biopsy probe. Xylazine HCl (0.05 mg/kg of body weight, IV) was administered to group-1 cows (n = 6), and endoscopy was repeated 5 minutes after administration of the drug. Xylazine (0.07 mg/kg, IV) was administered to group-2 cows (n = 6), and endoscopy was repeated 5 minutes after administration of the drug. Acepromazine maleate (0.035 mg/kg, iv) was administered to group-3 cows (n = 6), and endoscopy was repeated 10 minutes after administration of the drug. Responses to stimuli were scored as brisk (0), moderate (1), slow (2), and absent (3). Scores for responses to stimuli were compared, using the Wilcoxon signed-rank test for data within groups, and a general linear models procedure, using the Kruskal-Wallis test between groups. Interobserver agreement rates were generated for each group. A value of P<0.05 was considered significant. Xylazine profoundly changed laryngeal sensitivity and function at both dosages. The corniculate processes of the arytenoid cartilages were observed to be in a markedly adducted position after sedation. Response to stimuli was significantly (P = 0.03) slower than normal after sedation, using both dosages. Displacement of the soft palate dorsal to the epiglottis was persistent in 50% of the cows after stimulation tests subsequent to sedation with xylazine. Acepromazine had a mild effect on laryngeal sensitivity and function. The corniculate processes of the arytenoid cartilages were observed in paramedian position after sedation. Acepromazine did not significantly affect responses to stimuli. Effects of sedation on responses to stimuli were not significantly different for groups 1 and 2. However, effects for group 3 were significantly different from those for groups 1 and 2 (P = 0.006 and 0.004, respectively). Endoscopic evaluation of the proximal portion of the respiratory tract of cattle should be performed without sedation, when possible. If sedation is required to facilitate restraint for endoscopy, acepromazine maleate is recommended over xylazine on the basis of results of this study.

Effects of low doses of the neuroleptic drugs droperidol and zuclopenthixol, combined with a subanalgesic dose of the opioid mu-agonist, fentanyl, on mechanical nociceptive thresholds were evaluated in sheep. Intravenously administered droperidol (5 micrograms/kg of body weight) did not induce any change in the nociceptive thresholds when administered alone, but caused marked increase in threshold responses when combined with a subanalgesic dose of fentanyl (5 micrograms/ kg). Similarly, a combination of iv administered zuclopenthixol (100 micrograms/kg) and fentanyl induced significant (P < 0.05) antinociceptive effects, whereas zuclopenthixol administered iv alone had no effect on the threshold responses. Intrathecal administration of a low dose of droperidol (5-microgram total dose) combined with iv administered fentanyl also increased mechanical thresholds significantly (P < 0.05). These results indicate that interactions exist between dopaminergic and opioid systems in the processing of nociceptive information and that these effects may, at least partially, be mediated spinally.

To determine the effects of 9 sedative/anesthetic drug protocols on intradermal skin testing, an experimental state of type-I hypersensitivity was created. Intradermal skin tests were performed on 6 dogs, using positive and negative controls and a series of tenfold dilutions of ASC-1 allergen prior to drug administration. Approximately 4 hours later, the dogs were given 1 of the following drugs: acepromazine (low dose and high dose); ketamine hydrochloride with diazepam; thiamylal; oxymorphone; halothane; methoxyflurane; or isoflurane. The intradermal skin test then was repeated, and was scored objectively and subjectively. Objective scores were unaffected by any of the drugs. Subjective scores were affected in that acepromazine decreased wheal size and the induration of the intradermal skin test reaction sites.