Adrenergic antagonists bind but do not activate adrenoceptors. They act by preventing adrenergic agonist activity. Like the agonists, the antagonists differ in their spectrum of receptor interaction.
Phentolamine produces a competitive (revers-ible) blockade of both α1- and α2- receptors. α1-Antagonism and direct smooth muscle relaxation are responsible for peripheral vasodilation and a decline in arterial blood pressure. The drop in blood pressure provokes reflex tachycardia. This tachycardia is aug-mented by antagonism of presynaptic α2-receptors in the heart because α2-blockade promotes norepi-nephrine release by eliminating negative feedback. These cardiovascular effects are usually apparent within 2 min and last up to 15 min. As with all of the adrenergic antagonists, the extent of the response to receptor blockade depends on the degree of existing sympathetic tone. Reflex tachycardia and postural hypotension limit the usefulness of phentolamine to the treatment of hypertension caused by excessive α-stimulation (eg, pheochromocytoma, clonidinewithdrawal). Prazosin and phenoxybenzamine are examples of other alpha antagonists.
Phentolamine is administered intravenously as intermittent boluses (1–5 mg in adults) or as a con-tinuous infusion. To prevent tissue necrosis follow-ing extravasation of intravenous fluids containing an α-agonist (eg, norepinephrine), 5–10 mg of phen-tolamine in 10 mL of normal saline can be locally infiltrated. Phentolamine is packaged as a lyophi-lized powder (5 mg).