4.3 The adrenergic antagonist

4.3.1 Alpha antagonist

• Phentolamine produces a competitive (reversible) blockade of α -receptors. α 1-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. Dose: Intermittent boluses (1–5 mg in adults) intravenously. Site of clearance is not known.
• Prazosin is selective α1-blocker that antagonizes the vasoconstrictor effects of norepinephrine and epinephrine. Prazosin dilates both arterioles and veins. It is found useful for benign prostatic hypertrophy and hypertension. Be aware of their possible interactions with anesthetics.

4.3.2 Beta antagonist

β-adrenergic antagonists (i.e., b-blockers) are frequently taken by patients about to undergo surgery. Clinical indications for b-adrenergic blockade include ischemic heart disease, post infarction management, arrhythmias, hypertension, heart failure, migraine prophylaxis and thyrotoxicosis.

Adverse effects of beta blocker are life-threatening bradycardia, even asystole, may occur with β-blockade, and decreased contractility may precipitate CHF in patients with compromised cardiac function. In patients with bronchospastic lung disease, β2 blockade may be fatal. Diabetes mellitus is a relative contraindication to the long-term use of beta-adrenergic antagonists because warning signs of hypoglycemia (tachycardia and tremor) can be masked and because compensatory glycogenolysis is blunted. Overdose of β-blocking drugs may be treated with atropine.

• Propranolol (Inderal, Ipran) is a nonselective β-blocking drug. Arterial blood pressure is lowered by several mechanisms, including decreased myocardial contractility, lowered heart rate, and diminished rennin release. Cardiac output and myocardial oxygen demand are reduced. Propranolol is particularly useful during myocardial ischemia related to increased blood pressure and heart rate. Clearance of the drug can be affected by liver disease or altered hepatic blood flow. Propranolol is titrated to the desired effect, beginning with 0.5 mg and progressing by 0.5-mg increments every 3–5 min. Total doses rarely exceed 0.15 mg/kg.
• Esmolol is an ultrashort-acting selective β1-antagonist that reduces heart rate and, to a lesser extent, blood pressure. It has been successfully used to prevent tachycardia and hypertension in response to perioperative stimuli, such as intubation, surgical stimulation, and emergence. For example, esmolol (1 mg/kg) attenuates the rise in blood pressure and heart rate. Esmolol is as effective as propranolol in controlling the ventricular rate of patients with atrial fibrillation or flutter. Esmolol should be avoided in patients with sinus bradycardia, heart block greater than first degree, cardiogenic shock, or overt heart failure. Site of clearance is red blood cell esterase enzyme. Esmolol is administered as a bolus (0.2–0.5 mg/kg) for short-term therapy, such as attenuating the cardiovascular response to laryngoscopy and intubation. Long-term treatment is typically initiated with a loading dose of 0.5 mg/kg administered over 1 min, followed by a continuous infusion of 50 μg/kg/min to maintain the therapeutic effect.
• Labetalol: It blocks alpha-1 beta-1 and beta-2 receptors. This mixed blockade reduces peripheral vascular resistance and arterial blood pressure. Heart rate and cardiac output are usually slightly depressed or unchanged. Thus, labetalol lowers blood pressure without reflex tachycardia because of its combination of alpha and beta effects. Peak effect usually occurs within 5 min after an intravenous dose. Left ventricular failure, paradoxical hypertension, and bronchospasm have been reported. The initial recommended dose of labetalol is 0.1–0.25 mg/kg administered intravenously over 2 min. twice this amount may be given at 10-min intervals until the desired blood pressure response is obtained. Labetalol can also be administered as a slow continuous infusion (200 mg in 250 mL D5W) at a rate of 2 mg/min. Site of clearance is the liver