Farm Animal Anesthesia. Группа авторов

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Farm Animal Anesthesia - Группа авторов


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effects by their actions on both the central and peripheral α2 adrenoceptors. Stimulation of central (presynaptic) α2 adrenoceptors inhibits the release of catecholamines, thus reducing the response to excitatory input, and as a result sedation occurs. Peripheral (postsynaptic) α2 receptors are found in the vasculature, pancreatic islet cells, and uterine muscles. As a result, transient hypertension, hypoinsulinemia, hyperglycemia, and oxytocin‐like effect are often associated with the administration of an α2 agonist [33]. Other side effects associated with the administration of α2 agonists include direct myocardial depression and augmentation of parasympathetic stimulation resulting in a decrease in cardiac output, bradycardia, and hypotension. Up to a sixfold increase in urine output subsequent to a decrease in secretion of antidiuretic hormone is a common side effect of α2 agonists. The central muscle‐relaxing effect produced by α2 agonists is believed to be mediated through the inhibition of nerve impulse transmission at the internuncial neurons of the spinal cord, brain stem, and subcortical level of the brain [34]. Because of this, α2 agonists are often given in combination with anesthetics that do not provide adequate muscle relaxation for surgical procedures. For example, when ketamine is administered alone, it is often associated with muscle tremors, jerking activity, and rigidity; xylazine is administered concurrently to improve the muscle relaxation during ketamine anesthesia. All α2 agonists, though considered as pure α2 agonists, also have affinity for α1 receptors. The α2 : α1 selectivity ratios for xylazine, detomidine, romifidine, and medetomidine/dexmedetomidine are 160 : 1, 260 : 1, 340 : 1, and 1620 : 1, respectively [35, 36].

      2.3.1 Cattle

      2.3.1.1 Xylazine

      Epidural administration of xylazine to standing cattle produced effective perineal analgesia for 2.5–4 hours. Compared to epidural lidocaine, xylazine produced less disruption of hind limb motor function and provides a longer duration of perineal analgesia [46, 47]. Systemic effects like mild to moderate sedation and slight ataxia sometimes occur following caudal epidural administration of xylazine, which is a result of absorption of the drug into blood circulation from the injection site and/or diffusion of the drug into cerebrospinal fluid (CSF) with subsequent cranial migration of the drug into the CNS. Similarly, studies in humans [48] and dogs [49] showed that diffusion of epidurally administered morphine into the CSF and the subsequent migration of the drug up the spinal cord, rather than the total injected drug volume, were the primary factors responsible for the widespread analgesia of epidural morphine. IV administration of an α2 antagonist such as tolazoline reversed the systemic effects (sedation and ataxia) but did not affect the caudal epidural analgesia of xylazine [50]. It is believed that the epidural analgesia of xylazine is the result of the binding of xylazine to the α2 adrenoceptors located in the dorsal horn of the spinal cord, not the effect of xylazine on the central α2 adrenoceptors in the CNS [51, 52]. Therefore, IV or IM administration of an α2 antagonist does not affect the binding of an α2 agonist to the receptors in the epidural space due to low concentration of the α2 antagonist in the epidural space.

      2.3.1.2 Detomidine

      Caudal epidural administration of detomidine (0.04 mg/kg) induced perineal analgesia within 5 minutes following administration and lasted for 175 minutes [60]. In horses, caudal epidural detomidine has a slightly faster onset and shorter duration of perineal analgesia than xylazine, 12.5 ± 2.7 and 160 ± 8 minutes versus 13.1 ± 3.7 and greater than 165–180 minutes, respectively [61].

      Recently, sublingual detomidine gel with a concentration of 7.6 mg/ml in a 3‐ml syringe is available for horses to be used in the field or on the farm. When administered sublingually to horses, the oral bioavailability was 22% and the peak plasma concentration was approximately 40% that of the plasma concentration following IM administration. A mild to moderate degree of sedation occurred within 30–40 minutes and lasted 90–180 minutes [62, 63]. Minor procedures like grooming or examination


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