What are examples of beta blockers without sympathomimetic activity?

Beta Blockers Without Sympathomimetic Activity

Beta blockers without intrinsic sympathomimetic activity (ISA) include metoprolol, propranolol, atenolol, nadolol, timolol, bisoprolol, and carvedilol. These agents are preferred in clinical practice, particularly for patients with heart failure, post-myocardial infarction, or other cardiovascular conditions where reduction in heart rate and contractility is beneficial.

Characteristics of Beta Blockers Without ISA

Beta blockers without ISA are characterized by:

• No partial agonist activity at beta receptors
• Complete blockade of beta receptors without stimulation
• More pronounced reduction in resting heart rate compared to those with ISA
• Greater reduction in cardiac output at rest

Specific Examples

Beta-1 Selective (Cardioselective) Agents:

• Metoprolol - Available as tartrate (immediate-release) and succinate (extended-release) formulations 1
• Atenolol - Undergoes little hepatic metabolism, primarily eliminated by renal excretion 2
• Bisoprolol - Highly beta-1 selective

Non-selective Beta Blockers:

• Propranolol - Blocks both beta-1 and beta-2 receptors
• Nadolol - Long-acting non-selective agent
• Timolol - Commonly used in ophthalmic preparations

Combined Alpha and Beta Blockers:

• Carvedilol - Blocks beta-1, beta-2, and alpha-1 receptors; has no ISA 3
• Labetalol - Has alpha-1 and non-selective beta-blocking properties (but has some ISA)

Clinical Significance

Beta blockers without ISA are particularly important in:

1. Heart Failure Management: In patients with heart failure with reduced ejection fraction (HFrEF), guidelines specifically recommend beta blockers without ISA, particularly sustained-release metoprolol succinate, carvedilol, or bisoprolol due to their proven mortality benefit 4

2. Post-Myocardial Infarction: Beta blockers without ISA are strongly recommended for secondary prevention after MI 4

3. Hypertension Management: While not first-line agents unless the patient has ischemic heart disease or heart failure 4

Contrast with Beta Blockers with ISA

Beta blockers with intrinsic sympathomimetic activity include:

• Acebutolol
• Pindolol
• Penbutolol

These agents:

• Partially activate beta receptors while blocking catecholamine effects
• Produce less resting bradycardia
• May be better tolerated in patients with bradycardia or peripheral vascular disease 5
• Are generally avoided in patients with ischemic heart disease or heart failure 4

Important Considerations

• When selecting a beta blocker for heart failure or post-MI, choose one of the three agents proven to reduce mortality: sustained-release metoprolol succinate, carvedilol, or bisoprolol 4

• For patients with bronchospastic airway disease requiring a beta blocker, cardioselective agents (metoprolol, bisoprolol, atenolol) are preferred and should be initiated at low doses 4

• In patients with heart failure, beta blockers should be used cautiously with ACE inhibitors or ARBs 4

• Avoid abrupt discontinuation of beta blockers as this can lead to rebound hypertension or exacerbation of angina 4

Beta blockers without ISA are generally preferred over those with ISA for most cardiovascular indications, particularly when the therapeutic goal is to reduce heart rate, myocardial oxygen demand, and improve long-term survival in conditions like heart failure and post-myocardial infarction.