occur over a 24-hour period. The drug has negligible effects at α and muscarinic receptors; however, it may block some serotonin receptors in the brain, although the clinical significance is unclear.
It has no detectable partial agonist action at β receptors. Metoprolol, atenolol, and several other drugs (Table 10–2) are members of the β1-selective group. These agents may be safer in patients who experience bronchoconstriction in response to pro pranolol. Since their β1 selectivity is rather modest, they should be used with great caution, if at all, in patients with a history of asthma.
However, in selected patients with COPD, the benefits may exceed the risks, eg, in patients with myocardial infarction. Beta1-selective antagonists may be preferable in patients with diabetes or peripheral vascular disease when therapy with a β blocker is required, since
TABLE 10–3 Drugs used in open-angle glaucoma.
Drugs Mechanism Methods of Administration β2 receptors are probably important in liver (recovery from hypoglycemia) and blood vessels (vasodilation).
Nebivolol is the most highly selective β1-adrenergic receptor blocker, although some of its metabolites do not have this level of specificity. Nebivolol has the additional quality of eliciting vasodilation. This is due to an action of the drug on endothelial nitric oxide production. Nebivolol may increase insulin sensitivity and does not adversely affect lipid profile. Agents of this type are sometimes referred to as third-generation β-blocking drugs because they activate nitric oxide synthase. In patients with metabolic syndrome, for an equivalent reduction of blood pressure and heart rate, metoprolol, but not nebivolol, decreased insulin sensitivity and increased oxidative stress.
Timolol is a nonselective agent with no local anesthetic activity. It has excellent ocular hypotensive effects when administered topically in the eye. Nadolol is noteworthy for its very long duration of action; its spectrum of action is similar to that of timolol. Levobunolol (nonselective) and betaxolol (β1-selective) are also used for topical ophthalmic application in glaucoma; the latter drug may be less likely to induce bronchoconstriction than nonselective antagonists. Carteolol is a nonselective β-receptor antagonist.
Pindolol, acebutolol, carteolol, bopindolol, * oxprenolol, * celiprolol, * and penbutolol are of interest because they have partial β-agonist activity. They are effective in the major cardiovascular applications of the β-blocking group (hypertension and angina). Although these partial agonists may be less likely to cause bradycardia and abnormalities in plasma lipids than are antagonists, the overall clinical significance of intrinsic sympathomimetic activity remains uncertain. Pindolol, perhaps as a result of actions on serotonin signaling, may potentiate the action of traditional antidepressant medications. Acebutolol is also a β1-selective antagonist.
Celiprolol is a β1-selective antagonist with a modest capacity to activate β2 receptors. There is limited evidence suggesting that celiprolol may have less adverse bronchoconstrictor effect in asthma and may even promote bronchodilation.