A review of clinical approaches to antagonism of alpha₂‐adrenoreceptor agonists in the horse

Abstract

SummaryAlpha2-adrenoceptor agonists xylazine, romifidine, detomidine and, in some cases, medetomidine and dexmedetomidine, are fundamental drugs used in equine practice. There are situations where the undesirable pharmacodynamic effects (ataxia, prolonged sedation, bradycardia and ileus) or accidental overdose of these drugs may need to be antagonised. The α 2-adrenoceptor antagonists tolazoline, yohimbine and atipamezole can be used to antagonise undesirable effects. However, despite being effective, α 2-adrenoceptor antagonists are also not without undesirable pharmacodynamic effects. Excitement, muscle trembling and triggered inappropriate stress responses are a few of the more serious undesirable effects. Horses demonstrate a variable response to the antagonists thus recommending dose rates become fraught with difficulty. It is therefore recommended that the α 2-adrenoceptor antagonist should be titrated to the desired clinical effect. Consequently, other reversal agents, such as anticholinergics (atropine, glycopyrrolate and hyoscine), have been administered for the treatment of α 2-adrenoceptor agonist-induced bradycardia. Anticholinergics cannot be recommended for routine use in horses due to the undesirable cardiovascular effects and potentiation of α 2-adrenoceptor agonist-induced gastrointestinal hypomotility. Novel peripheral acting α 2-adrenoceptor antagonists, such as MK-467, are currently under scrutiny in veterinary anaesthesia in an effort to antagonise the undesirable effects of α 2-adrenoceptor agonists without compromising on the level of sedation. This review examines the current literature on the α 2-adrenoceptor antagonists used in horses and makes recommendations on how to use these drugs safely in an attempt to prevent undesirable pharmacodynamic effects.

Detomidine and xylazine, at different doses, in donkeys (Equus asinus)

“…El-Kammar & Gad (2014) observed classical signs of ataxia in asinines with detomidine after 15 minutes of injecting the drug. These results reinforce the direct relationship of the sedative effects of these drugs and ataxia (Zeiler, 2015). Also, most studies evaluating the sedative effects of these drugs on equids have cited the degree of ataxia as one of the main variables used (Ringer et al, 2013;Gozalo-Marcilla et al, 2015;Gozalo-Marcilla et al, 2017).…”

Evaluation of Medetomidine-Ketamine for Immobilization of Feral Horses in Romania

“…To keep overall immobilization costs down, the effective medetomidine:atipamezole ratio used (1:1.2) was lower than reported in other studies for equids [Equus caballus domesticus; 1:5 to 1:10 (25); Equus ferus asinus, 1:2.5 (8); Equus przewalskii; 1:2 (7); Equus ferus caballus; 1:2; (4)] or other wild animal species [1:5; (6)]. However, the dose of 25 mg atipamezole per animal gave an acceptable recovery and supported the suggestion that recommended doses for domestic horses tend to be larger than clinically necessary (25). Most recoveries were uneventful, with one or more attempts for standing, however, the horses presented prolonged ataxia, remaining stationary for varied periods.…”

The use of hyoscine N‐butylbromide to treat intraoperative bradycardia during isoflurane anaesthesia in three horses

“…To the author's knowledge, this is the first time that hyoscine NBB has been reported for the treatment of bradyarrhythmia in isoflurane-anaesthetised horses under clinical conditions. When reversal of vagally mediated bradycardia is indicated in anaesthetised horses, hyoscine NBB may be considered as an alternative to atropine as a positive chronotropic agent (Pimenta et al 2011;Zeiler 2015). Although the positive chronotropic action of hyoscine is of shorter duration than that of atropine, hyoscine NBB may be able to reverse vagally mediated bradycardia without causing prolonged reductions in intestinal motility.…”