Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications

The α-2 adrenergic receptor agonists have been used for decades to treat common medical conditions such as hypertension; attention-deficit/hyperactivity disorder; various pain and panic disorders; symptoms of opioid, benzodiazepine, and alcohol withdrawal; and cigarette craving.¹ However, in more recent years, these drugs have been used as adjuncts for sedation and to reduce anesthetic requirements. This review will provide an historical perspective of this drug class, an understanding of pharmacological mechanisms, and an insight into current applications in clinical anesthesiology.Key Words: Procedural sedation, General anesthesia, Alpha-2 agonists, Clonidine, DexmedetomidineIn early scientific theory of adrenergic mechanisms, it was believed that adrenergic receptors were classified into 2 groups: those whose actions resulted in either excitation or inhibition of effector cells.² This theory was the accepted concept until Ahlquist² demonstrated that there were 2 subtypes of receptors in the class, which he termed α and β (2 Further study led researchers to discover that one of the α receptors inhibited neurotransmitter release from the presynaptic neuron.³ The α-receptor antagonists prazosin and yohimbine were used to further subclassify these receptors as α-1 and α-2.⁴ Later, many α-2 adrenergic agonists were developed for use in the clinical setting, including their use as anesthesia adjuncts. The use of α-2 agonists as adjuncts gained popularity when early reports by Brodsky and Bravo⁵ found that withholding a single dose of clonidine prior to anesthesia caused a patient to experience an acute hypertensive crisis. It was discovered that α-2 agonists produce effects within both the central and peripheral nervous systems. Centrally within the locus ceruleus, for example, α-2 agonists are able to produce sedation, analgesia, and euphoric effects and partially block acute withdrawal symptoms in chronic opioid users.⁴ More potent α-2 selective drugs, such as dexmedetomidine, have been formulated for clinical use as sole sedative agents or as adjuncts to drastically reduce the patient''s requirement for additional sedatives or general anesthetics. Also, α-2 agonists are gaining popularity in children''s hospitals throughout the United States as a preventative measure of and treatment modality for emergence delirium after general anesthesia.⁶

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Open in a separate windowAdrenergic Receptor Subtypes and Their Physiologic Functions