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
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
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).