Beta Blocker, Nonselective

Hypersensitivity to bucindolol or other beta-adrenergic blockers; bronchospastic disease; bradycardia; cardiogenic shock; greater than first-degree A-V block (except in patients with a functioning artificial pacemaker)

Use with caution in patients with multiple allergies, ventricular tachycardia, first-degree A-V block, hypotension, bradycardia, Raynaud's syndrome, peripheral vascular disease, hyperthyroidism, cardiac tamponade, diabetes mellitus, myasthenia gravis, liver or renal disease, or pregnancy. Bucindolol has not been demonstrated to be of benefit in patients with Class III-IV congestive heart failure (BEST study).

Cardiovascular: Postural hypotension, facial flushing, sinus bradycardia

Central nervous system: Dizziness, headache, fatigue

Gastrointestinal: Nausea, vomiting, dyspepsia, abdominal cramps

Neuromuscular & skeletal: Myalgia

Respiratory: Bronchospasm

Anticipated to be similar to other beta-blockers.

Ampicillin, in single doses of 1 gram, decrease bucindolol's pharmacologic actions.

Antacids (magnesium-aluminum, calcium antacids or salts) may reduce the bioavailability of bucindolol.

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.

Glucagon: Bucindolol may blunt the hyperglycemic action of glucagon.

Insulin and oral hypoglycemics: Bucindolol masks the tachycardia that usually accompanies hypoglycemia.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.

Nonselective beta-adrenergic blocker with vasodilatory activity; small amount of affinity for alpha₁ or alpha₂ receptors

Onset of action: 1 hour

Metabolism: Hepatic metabolism to an active metabolite (5-hydroxybucindolol) and 2 inactive metabolites (6-hydroxybucindolol and indolyl-t-butylamine)

Bioavailability: Oral: 30%

Half-life: 3.6 hours (parent compound); 0.15 hour (5-hydroxybucindolol)

Congestive heart failure: 6.25 mg twice daily for 1 week followed by doubling of dose weekly, as tolerated, to a maximum dose of 100 mg twice daily. Note: The BEST study, presented in November 1999 at the AHA Scientific sessions, showed no benefit of bucindolol in patients with Class III-IV CHF.

Hypertension: 50 mg 3 times/day up to 200 mg 3 times/day

Elevated CPK levels (probably relatable to skeletal muscle origin) have been noted in hypertensive patients on bucindolol.

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). Data from the Beta-blockers Evaluation Survival Trial (BEST) indicate bucindolol did not provide a survival benefit in patients with NYHA class III-IV CHF (Reported at the AHA Scientific sessions - November 1999). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

"Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure," Am J Cardiol, 1999, 83(2A):1A-38A.

Domanski M, 72nd Scientific Sessions of the American Heart Association, Plenary Session XII: Late-Breaking Clinical Trials, "BEST (Beta-Blockers Evaluation Survival Trial)", November 10, 1999 (abstract).

Gibbons RJ, Chatterjee K, Daley J, et al, "ACC/AHA/ACP-ASIM Guidelines for the Management of Patients With Chronic Stable Angina: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines," J Am Coll Cardiol, 1999, 33(7):2092-197.

Ryan TJ, Anderson JL, Antman EM, et al, "ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)," J Am Coll Cardiol, 1996, 28(5):1328-428.