αAntagonists produce orthostatic hypotension, tachycardia, and miosis.
Phentolamine is a nonselective and competitive antagonist at α1 and α2 receptors that is typically administered (2–5 mg IV) until adequate control of blood pressure is achieved. Tachycardia reflects continued presynaptic release of norepinephrine owing to α2-receptor blockade.
Prazosin is a selective postsynaptic α1 antagonist that leaves intact the negative feedback mechanism for norepinephrine release that is mediated by presynaptic α2 activity. This drug is useful in the preoperative preparation of patients with pheochromocytoma.
An important class of drugs is beta-blockers, which are indicated for the treatment of coronary artery disease, hypertension, heart failure, and tachyarrhythmias. They have a primary role in treatment of patients after myocardial infarction (MI). Beta-blockers decrease mortality in patients with heart failure caused by left ventricular systolic dysfunction. They also reduce the incidence of perioperative MI and may be useful perioperatively in high-risk patients undergoing vascular and other high-risk surgical procedures.
The POISE study concluded that perioperative beta-blockade reduced the risk of cardiac events but increased the risk of all-cause mortality and major strokes.
Selective beta-blockade (cardioselective) implies greater safety in the treatment of patients with obstructive pulmonary disease, diabetes mellitus, and peripheral vascular disease because β2-agonist effects (bronchodilation, vasodilation) are presumably maintained. The clinical significance of membrane-stabilizing activity (a local anesthetic effect on myocardial cells at high doses) and intrinsic sympathomimetic activity (partial β-agonist activity at low doses) has not been documented. Because of their selectivity, the use of beta-blockers has extended to include treatment of congestive heart failure.
Propranolol is a nonselective βantagonist that may be administered in single IV doses of 0.1 to 0.5 mg (maximum dose, ~2 mg) to slow heart rate during anesthesia. Additive negative inotropic or chronotropic effects with inhaled or injected anesthetics are likely to occur but have not been a significant clinical problem.
Timolol is administered as a topical preparation for the treatment of glaucoma. There may be sufficient systemic absorption to cause bradycardia and hypotension that are resistant to reversal with atropine.
Mixed Antagonists
Labetalol produces selective α1- and nonselective β-antagonist effects. Administered as a single dose (0.05–0.15 mg/kg IV over 2 minutes), this drug is useful in controlling hypertension and tachycardia in response to painful stimulation during general anesthesia. Although the magnitude is less than with βantagonists, worsening of congestive heart failure or appearance of bronchospasm may occur after administration of labetalol.