XYLAZINE

XYLAZINE

α₂-adrenoceptor agonists (xylazine, romifidine, detomidine, medetomidine), which are the most widely used drugs for immobilizing ruminants, have most of the desirable properties of opioids but induce few of their undesirable actions. U

Unlike opioids, α₂-adrenoceptor agonists do not cause excitement and only induce minimal respiratory depression in ruminants. They are not FDA-controlled substances and therefore do not require extensive record keeping. In addition, α₂-adrenoceptor agonists are potent analgesics that induce dose-related sedation, thereby decreasing the required dose of primary anesthetic. When the proper dose is administered, these agonists do not cause excitement or profound respiratory depression.

Xylazine, the most notable α₂-adrenoceptor agonist, induces analgesia, sedation, and muscle relaxation by activating centrally located α₂-adrenoceptors

·         Xylazine’s activation of α₂-adrenoceptors located in the central nervous system (CNS) induces analgesia, sedation, muscle relaxation, anxiolysis, sympatholysis, and other responses. 

·         In addition to centrally located receptors, receptors are present in peripheral tissue (e.g., the gastrointestinal [GI] tract, uterus, kidney, and platelets).

·         Activation of the α₂-adrenoceptors in the GI tract of ruminants results in ruminal hypomotility and increased GI fecal waste material.2

·         The cardiovascular actions of α2-adrenoceptor agonists include increased blood pressure (BP) and decreased heart rate (HR), the latter being characterized by sinus bradycardia and/or atrioventricular blockade

·          Xylazine can be safely administered by the intramuscular, intravenous , and epidural routes.

·          Cattle are apparently one of the most sensitive species to the sedative and immobilizing actions of xylazine and therefore require a rather small dose. cattle are approximately 5 to 10 times more sensitive than horses to a given dose of xylazine. Sheep and goats are apparently slightly more sensitive than cattle or llamas.

·          After cattle have been injected with xylazine, a dose-dependent, sleep like state occurs and often persists for 1 to 2 hours, although the duration of analgesia is much shorter (20 to 35 minutes) depending on thedose administered. I

·         In most domestic species, xylazine  minimally affects respiratory function at recommended doses.1 In contrast, caution is advised when administering xylazine or any other α2-adrenoceptor agonist to young ruminants in high singular or cumulative doses or combined with potent cardiorespiratory-depressant anesthetics (e.g., heavy doses of thiopental or pentobarbital). 

·          Special precautions should be taken when mature ruminants receive xylazine before improper fasting because of the potential for developing life-threatening ruminal tympany.

·          A guaifenesin–ketamine–xylazine combination is an established anesthetic widely used in ruminants. Guaifenesin acts centrally by inducing skeletal muscle relaxation and mild sedation without analgesia. Analgesia and narcosis are enhanced by combining ketamine and xylazine with guaifenesin.

·          A triple-drip drug combination can be prepared by adding ketamine (2 mg/ml) and xylazine (0.1 mg/ml) to a 5% solution of guaifenesin (usually prepared in 5% glucose in water).

·          To induce anesthesia in patients weighing less than 250 kg (e.g., calves, llamas, sheep, and goats), the triple-drip preparation should be injected using a large syringe rather than by intravenous drip. The induction dose is 0.5 to 1.0 ml/kg, depending on the patient’s size and the rate of injection.1 Anesthesia can be maintained by a continuous infusion rate of 1.0 of 2.0 ml/kg/hr

·          Failure to achieve optimum sedation with α2-adrenoceptor agonists may be caused by preexisting stress,  fear, excitement, or pain because all of these signs are associated with increased endogenous concentrations of circulating catecholamines that can interfere with reductions in the release of excitatory neurotransmitters, a response induced by α2-adrenoceptor agonists.

·           The intramuscular dose of xylazine used to induce recumbency in docile beef cows and calves is approximately 0.22 mg/kg, and the intravenous dose is 0.11 mg/kg. In large bulls (e.g., weighing 900 kg or more), the intramuscular dose should be decreased to 0.18 mg/kg and the intravenous dose to 0.08 mg/kg

·         The most satisfactory use of xylazine or other α2-adrenoceptor agonists is achieved when given to calm, quiet patients in nonstressful surroundings with minimal environmental stimuli.

·         In cattle, caudal epidural injection of xylazine produces analgesia that lasts 2 to 2.5 times longer than an equivalent dose of lidocaine.1,26 Intravenous tolazoline (0.3 mg/kg) antagonizes the sedative actions of epidural xylazine. Analgesia caudal to the injection site of xylazine persists27 because of the potent local anesthetic action of xylazine.

·          Development of specific antagonists has extended he safe use of α2-adrenoceptor agonists in ruminants. The most notable antagonists are tolazoline, yohimbine, and atipamezole.

·         Tolazoline is an imidazoline derivative with α1- and α2-adrenoceptor antagonistic activity. This drug has been safely and extensively used to antagonize xylazine induced sedation and initiate arousal in various species that are in a depressed state from anesthetic combinations that contain α2-adrenoceptor agonists.

·          The recommended dose of intravenous tolazoline required to antagonize xylazine sedation and promote prompt arousal in cattle ranges from 1.1 to 2.2 mg/kg, depending on the elapsed time since xylazine was administered.27,35–37 The highest recommended intravenous dose (2.2 mg/kg) should be reserved for treating a cow that was accidentally overdosed, is suffering from bloat, or requires drug reversal shortly after xylazine administration.