Beta-Blocker Classification and List
Beta-blockers are categorized into three generations based on their receptor selectivity and additional pharmacologic properties, with specific agents approved for cardiovascular conditions including bisoprolol, carvedilol, and metoprolol in the United States. 1
First-Generation (Non-Selective) Beta-Blockers
These agents block both β1-adrenoceptors (primarily cardiac) and β2-adrenoceptors (bronchial and vascular smooth muscle) without additional vasodilatory properties 2, 3:
- Propranolol - Non-selective agent with proven mortality benefit post-myocardial infarction; has low lipophilicity limiting CNS penetration 4, 3
- Nadolol - Non-selective blocker with variable oral absorption (approximately 30%); lacks intrinsic sympathomimetic activity and has minimal direct myocardial depressant effects 2
- Timolol - Non-selective agent with demonstrated post-infarction mortality benefit; also used topically for glaucoma 5, 3
Important caveat: Non-selective agents cause more bronchoconstriction and vasoconstriction than selective agents, and should be avoided in patients with asthma 1, 5. They are associated with increased risk of new-onset diabetes and unfavorable lipid changes 1.
Second-Generation (β1-Selective) Beta-Blockers
These agents preferentially block β1-adrenoceptors in cardiac tissue, reducing bronchoconstrictive effects 3, 6:
- Metoprolol - β1-selective agent with FDA indication for heart failure; proven mortality benefit post-infarction and in heart failure; considered safe in pregnancy 1, 7, 3
- Bisoprolol - β1-selective agent available in the United States with demonstrated mortality benefit in heart failure class II-III 1, 8
- Atenolol - β1-selective but hydrophilic agent; inferior outcomes in two major trials (LIFE and ASCOT) with unfavorable metabolic effects similar to non-selective agents 1
Critical distinction: High β1-selectivity agents like bisoprolol and metoprolol are safe and beneficial in COPD patients with cardiovascular disease, potentially reducing COPD exacerbations 8. Atenolol's low β1-selectivity may worsen pulmonary function 8.
Third-Generation (Vasodilating) Beta-Blockers
These agents combine beta-blockade with additional vasodilatory mechanisms through α1-blockade, β2-agonism, or nitric oxide release 9, 6, 10:
Non-Selective with α1-Blockade:
- Carvedilol - Non-selective β-blocker with α1-blocking properties; FDA-approved for heart failure with proven mortality benefit; possesses antioxidant effects and favorable effects on insulin resistance and glycemic control 1, 11, 9, 3
- Labetalol - Non-selective β-blocker with α1-blocking activity; useful in hypertensive emergencies; considered safe in pregnancy 1, 12
β1-Selective with Nitric Oxide-Mediated Vasodilation:
- Nebivolol - β1-selective with nitric oxide-mediated vasodilatory effects; does not worsen glucose tolerance even when combined with hydrochlorothiazide; preferred in metabolic syndrome 11, 9
Key advantage: Vasodilating beta-blockers minimize adverse effects including improved insulin resistance, better lipid profiles, reduced peripheral circulatory disturbances, and decreased erectile dysfunction compared to conventional agents 6, 10.
Clinical Selection Algorithm
For heart failure (HFrEF): Use carvedilol, metoprolol, or bisoprolol - all have proven mortality reduction of approximately 30% and hospitalization reduction of 40% in class II-III heart failure 1
For post-myocardial infarction: Propranolol, timolol, metoprolol, or carvedilol (if left ventricular dysfunction present) have demonstrated mortality benefit 3
For hypertension with COPD: Use high β1-selective agents (bisoprolol or metoprolol); target heart rate 60-70 beats/min 8
For hypertension with diabetes: Prefer vasodilating agents (carvedilol or nebivolol) over traditional beta-blockers due to more favorable metabolic profile; carvedilol may have superior glycemic control effects compared to metoprolol 11
For hypertension with metabolic syndrome: Choose vasodilating beta-blockers (carvedilol, nebivolol) over metoprolol 11
For pregnancy: Metoprolol and labetalol are considered safe 1, 7
Common Pitfalls to Avoid
- Do not avoid beta-blockers entirely in COPD patients - cardioselective agents are safe and reduce mortality in this population 8
- Do not use atenolol as first-line - inferior outcomes in major trials despite β1-selectivity 1
- Do not use agents with intrinsic sympathomimetic activity in heart failure - no beneficial effect demonstrated 1
- Distinguish between COPD and asthma - true asthma remains a stronger contraindication even for selective agents 8
- Monitor for excessive bradycardia in elderly - lowering heart rate too much can cause serious adverse events 7