Alpha2 adrenergic agonists

The alpha2 agonist family of drugs is notable for its predictable and quick onset of effective sedation. Alpha2 agonists additionally provide muscle relaxation and analgesia. While they do have significant dose dependent cardiovascular effects, they are reversible with alpha2 antagonists; atipamezole, tolazoline and yohimbine. 

Xylazine was first formulated in 1962 as a potential antihypertensive but was never approved for use in humans. It was not until 20 years later, in 1982, that clinicians began to understand xylazine’s impressive sedative and analgesic effects36. Subsequently, detomidine, romifidine, medetomidine and, finally, dexmedetomidine, were developed with more selectivity for the alpha 2 adrenergic receptor versus the alpha 1 thus improving the potency and safety profile of this class of drugs.

Initial effects associated with binding of these drugs to alpha2 receptors include peripheral vasoconstriction which can lead to an increase in blood pressure and reflex bradycardia followed by centrally mediated bradycardia and hypotension. Excitement and agitation is associated with high doses of alpha2 agonists, especially xylazine, which also has an affinity for alpha1 receptors. 

Other characteristics of alpha2 agonist administration include transient hyperglycemia37, increased urine output, and decreased GI motility38..A common arrhythmia associated with alpha2 agonist administration is second degree atrioventricular block. As for reversibility, tolazoline and yohimbine are primarily used to reverse xylazine, whereas atipamezole is used for medetomidine and dexmedetomidine.

Due to their significant cardiovascular effects, alpha2 agonists have typically been indicated only for healthy patients, although recent applications in human critical care units may have promise in our more critical patients.  

All alpha2 agonists have great potential to reduce the required amount of induction and maintenance drugs. In some species (horses), xylazine has been shown to control pain better than some opioids and NSIADs39. Xylazine remains recommended as the antiemetic of choice for cats.