α-agonists

α-agonists

1. Phenylephrine is a direct-acting α₁-agonist at typical clinical doses of 40 to 200 μg/min. Phenylephrine causes both arterial and venous vasoconstriction. This dual action increases venous return and mean arterial blood pressure, frequently resulting in reflex bradycardia. Phenylephrine maintains CO in patients with normal myocardial function but may decrease cardiac performance in the presence of myocardial ischemia. Phenylephrine has a short duration of action, which makes it easily titratable.
2. Midodrine is an orally administered α₁-agonist approved for the treatment of symptomatic orthostatic hypotension at doses of 2.5 to 10 mg TID. It is a prodrug that mediates its clinical effect through its active metabolite, desglymidodrine. Midodrine is increasingly used off-label to prevent hemodialysis-related hypotension and to facilitate weaning of vasopressors in the ICU despite limited data on safety and efficacy. Mesenteric ischemia associated with midodrine administration has been reported.
3. Clonidine is a centrally acting antihypertensive with relative selectivity for α₂-adrenoreceptors. Its actions include reducing sympathetic tone, increasing parasympathetic tone, reducing anesthetic and analgesic requirements, causing sedation, and decreasing salivation. It may be administered intravenously, intramuscularly, orally, transcutaneously, epidurally, and intrathecally. Abrupt cessation of clonidine is associated with rebound hypertension, thus doses should be gradually tapered when discontinuing.
4. Dexmedetomidine is a selective α₂-adrenoreceptor agonist approved for intravenous (IV) sedation of mechanically ventilated patients in an intensive care setting. Its action on presynaptic receptors inhibits the release of norepinephrine, and its activation of postsynaptic α₂-receptors in the CNS inhibits sympathetic activity. These effects decrease blood pressure and heart rate. Dexmedetomidine offers potential advantages over other sedatives, including reduced respiratory depression, delirium, and hypotension.