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Summary

Cardiopulmonary and behavioral responses to detomidine, a potent α2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (X̄ ± sd for age and body weight, 6 ± 2 years, and 531 ± 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 ± 0.5 (infusion 1), 7.2 ± 3.5 (infusion 2), 19.1 ± 5.1. (infusion 3), and 42.9 ± 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system.

Detomidine caused concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 ± 7 beats/min, 65 ± 11 ml·kg of body weight−1·min−1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart rate = −4.7 [loge detomidine concentration] + 44.3, P < 0.01; cardiac index = −10.5 [loge detomidine concentration] + 73.6, P < 0.01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arterial blood pressure increased significantly from 118 ± 11 mm of Hg at baseline to 146 ± 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemic vascular resistance (baseline, 182 ± 28 mm of Hg·ml−1·min−1·kg−1) increased significantly during infusions 3 and 4 (to 294 ± 79 and 380 + 58, respectively). Plasma atrial natriuretic peptide concentration was significantly increased with increasing detomidine concentration (20.4 ± 3.8 pg/ml at baseline to 33.5 ± 9.1 at infusion 4). There were few significant changes in respiration rate and arterial blood gas and pH values. We conclude that maintenance of steady-state detomidine plasma concentrations resulted in cardiopulmonary changes that were quantitatively similar to those induced by detomidine bolus administration in horses.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To assess the pharmacokinetics and pharmacodynamics of morphine in llamas.

Animals—6 healthy adult llamas.

Procedures—Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis.

Results—Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean ± SD, 25.3 ± 6.9 mL/min/kg and 27.3 ± 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 ± 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score.

Conclusions and Clinical Relevance—Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.

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in American Journal of Veterinary Research