Pharmacology of Alpha-2 Agonists Applied to Sedation, Sleep, and Analgesia

The alpha agonists clonidine and dexmedetomidine differ from gamma-aminobutyric acid agonists in mechanism for achieving sedation, analgesia, and promoting sleep. They may reduce delirium prevalence and duration. α-2 agonists act centrally, spinally, and peripherally to modulate multiple sedative, analgesic, and inflammatory pathways. They reduce sympathetic activity, which mediates the most frequent side-effects of bradycardia and hypotension. Dexmedetomidine has 8-times higher α-2:α-1 receptor affinity than clonidine, and greater evidence for effectiveness. The pharmacokinetic profile is predictable, whereas clonidine elimination is unpredictable in critical illness. Current costs are comparable. The risk/benefit balance for both agents remains uncertain and is likely patient specific.