Metoprolol and atenolol, which are cardioselective, are the most widely used β blockers in the treatment of hypertension. Metoprolol is approximately equipotent to propranolol in inhibiting stimulation of β1 adrenoceptors such as those in the heart but 50to 100-fold less potent than propranolol in blocking β2 receptors. Relative cardioselectivity is advantageous in treating hypertensive patients who also suffer from asthma, diabetes, or peripheral vascular disease. Although cardioselectivity is not complete, metoprolol causes less bronchial constriction than propranolol at doses that produce equal inhibition of β1-adrenoceptor responses. Metoprolol is extensively metabolized by CYP2D6 with high first-pass metabolism. The drug has a relatively short half-life of 4–6 hours, but the extended-release preparation can be dosed once daily (Table 11–2). Sustained-release metoprolol is effective in reducing mortality from heart failure and is particularly useful in patients with hypertension and heart failure.
Atenolol is not extensively metabolized and is excreted primarily in the urine with a half-life of 6 hours; it is usually dosed once daily. Atenolol is reported to be less effective than metoprolol in preventing the complications of hypertension. A possible reason for this difference is that once-daily dosing does not maintain adequate blood levels of atenolol. The usual dosage is 50–100 mg/d. Patients with reduced renal function should receive lower doses.
Nadolol, Carteolol, Betaxolol, & Bisoprolol
Nadolol and carteolol, nonselective β-receptor antagonists, are not appreciably metabolized and are excreted to a considerable extent in the urine. Betaxolol and bisoprolol are β1-selective blockers that are primarily metabolized in the liver but have long half-lives. Because of these relatively long half-lives, these drugs can be administered once daily. Nadolol is usually begun at a dosage of 40 mg/d, carteolol at 2.5 mg/d, betaxolol at 10 mg/d, and bisoprolol at 5 mg/d. Increases in dosage to obtain a satisfactory therapeutic effect should take place no more often than every 4 or 5 days. Patients with reduced renal function should receive correspondingly reduced doses of nadolol and carteolol.
Pindolol, Acebutolol, & Penbutolol
Pindolol, acebutolol, and penbutolol are partial agonists, ie, β blockers with some intrinsic sympathomimetic activity. They lower blood pressure but are rarely used in hypertension.
Labetalol, Carvedilol, & Nebivolol
These drugs have both β-blocking and vasodilating effects. Labetalol is formulated as a racemic mixture of four isomers (it has two centers of asymmetry). Two of these isomers—the (S,S)and (R,S)-isomers—are relatively inactive, a third (S,R)is a potent α blocker, and the last (R,R)is a potent β blocker. Labetalol has a 3:1 ratio of β:α antagonism after oral dosing. Blood pressure is lowered by reduction of systemic vascular resistance (via α blockade) without significant alteration in heart rate or cardiac output. Because of its combined αand β-blocking activity, labetalol is useful in treating the hypertension of pheochromocytoma and hypertensive emergencies. Oral daily doses of labetalol range from 200 to 2400 mg/d. Labetalol is given as repeated intravenous bolus injections of 20–80 mg to treat hypertensive emergencies.