>10%: Central nervous system: Fatigue (11%)

1% to 10%:

Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF

Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyperesthesia, hypoesthesia, impotence

Dermatologic: Rash (2%), pruritus

Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), vomiting, abdominal pain

Genitourinary: Micturition frequency (3%), dysuria, nocturia, impotence (2%)

Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), back pain, joint pain

Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain

Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing

<1% (Limited to important or life-threatening): Increased transaminases, increased bilirubin, increased alkaline phosphatase, hepatotoxic reaction, ventricular arrhythmia, AV block, facial edema, xerostomia, anorexia, impotence, urinary retention, cold extremities, systemic lupus erythematosus, palpitation, exacerbate pre-existing renal insufficiency

Postmarketing and/or case reports: Pleurisy, pulmonary granulomas, pneumonitis, lichen planus, lupus erythematosus, drug-induced lupus-like syndrome

Potential adverse effects (based on experience with other beta-blocking agents) include reversible mental depression, disorientation, catatonia, short-term memory loss, emotional lability, slightly clouded sensorium, laryngospasm, respiratory distress, allergic reactions, erythematous rash, agranulocytosis, purpura, thrombocytopenia, mesenteric artery thrombosis, ischemic colitis, alopecia, Peyronie's disease, claudication

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

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

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

Glucagon: Acebutolol may blunt the hyperglycemic action of glucagon.

Insulin and oral hypoglycemics: Acebutolol masks the tachycardia from 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.

Food: Peak serum acebutolol levels may be slightly decreased if taken with food.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). avoid yohimbe, ginseng (may worsen hypertension).

Onset of action: 1-2 hours

Duration: 12-24 hours

Absorption: Oral: 40%

Protein binding: 5% to 15%

Metabolism: Extensive first-pass effect

Half-life elimination: 6-7 hours

Time to peak: 2-4 hours

Excretion: Feces (~55%); urine (35%)

Adults:

Hypertension: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses

Ventricular arrhythmias: Initial: 400 mg/day; maintenance: 600-1200 mg/day in divided doses

Elderly: Initial: 200-400 mg/day; dose reduction due to age related decrease in Clcr will be necessary; do not exceed 800 mg/day

Dosing adjustment in renal impairment:

Clcr 25-49 mL/minute/1.73 m²: Reduce dose by 50%.

Clcr<25 mL/minute/1.73 m²: Reduce dose by 75%.

Dosing adjustment in hepatic impairment: Use with caution.

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.

Unstable angina/non-ST-segment elevation MI: In the treatment of unstable angina/non-ST-segment elevation MI, a beta-blocker, with the first dose administered intravenously if there is ongoing chest pain, followed by oral administration, is recommended (in the absence of contraindications).

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). Acebutolol exhibits ISA. 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.

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