"What are beta blockers and how do they work?
Beta blockers, also known as beta-adrenergic blocking agents, are a class of drugs that works by blocking the neurotransmitters norepinephrine and epinephrine from binding to receptors. "...
Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by β-adrenergic receptor blockade may precipitate more severe failure. Although β-blockers should be avoided in overt cardiac failure, Sectral can be used with caution in patients with a history of heart failure who are controlled with digitalis and/or diuretics. Both digitalis and Sectral impair AV conduction. If cardiac failure persists, therapy with Sectral should be withdrawn.
In Patients Without A History Of Cardiac Failure
In patients with aortic or mitral valve disease or compromised left ventricular function, continued depression of the myocardium with β-blocking agents over a period of time may lead to cardiac failure. At the first signs of failure, patients should be digitalized and/or be given a diuretic and the response observed closely. If cardiac failure continues despite adequate digitalization and/or diuretic, Sectral therapy should be withdrawn.
Exacerbation Of Is Chemic Heart Disease Following Abrupt Withdrawal
Following abrupt cessation of therapy with certain β-blocking agents in patients with coronary artery disease, exacerbation of angina pectoris and, in some cases, myocardial infarction and death have been reported. Therefore, such patients should be cautioned against interruption of therapy without a physician's advice. Even in the absence of overt ischemic heart disease, when discontinuation of Sectral is planned, the patient should be carefully observed, and should be advised to limit physical activity to a minimum while Sectral is gradually withdrawn over a period of about two weeks. (If therapy with an alternative β-blocker is desired, the patient may be transferred directly to comparable doses of another agent without interruption of β-blocking therapy.) If an exacerbation of angina pectoris occurs, antianginal therapy should be restarted immediately in full doses and the patient hospitalized until his condition stabilizes.
Peripheral Vascular Disease
Treatment with β-antagonists reduces cardiac output and can precipitate or aggravate the symptoms of arterial insufficiency in patients with peripheral or mesenteric vascular disease. Caution should be exercised with such patients, and they should be observed closely for evidence of progression of arterial obstruction.
PATIENTS WITH BRONCHOSPASTIC DISEASE SHOULD, IN GENERAL, NOT RECEIVE A β-BLOCKER. Because of its relative β1 -selectivity, however, low doses of Sectral may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate, alternative treatment. Since β1-selectivity is not absolute and is dose-dependent, the lowest possible dose of Sectral should be used initially, preferably in divided doses to avoid the higher plasma levels associated with the longer dose-interval. A bronchodilator, such as theophylline or a β2- stimulant, should be made available in advance with instructions concerning its use.
Anesthesia And Major Surgery
The necessity, or desirability, of withdrawal of a - blocking therapy prior to major surgery is controversial. -adrenergic receptor blockade impairs the ability of the heart to respond to - adrenergically mediated reflex stimuli. While this might be of benefit in preventing arrhythmic response, the risk of excessive myocardial depression during general anesthesia may be enhanced and difficulty in restarting and maintaining the heart beat has been reported with beta-blockers. If treatment is continued, particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichlorethylene, and it is prudent to use the lowest possible dose of Sectral. Sectral, like other -blockers, is a competitive inhibitor of -receptor agonists, and its effect on the heart can be reversed by cautious administration of such agents (e.g., dobutamine or isoproterenol—see OVERDOSAGE). Manifestations of excessive vagal tone (e.g., profound bradycardia, hypotension) may be corrected
Diabetes And Hypoglycemia
β-blockers may potentiate insulin-induced hypoglycemia and mask some of its manifestations such as tachycardia; however, dizziness and sweating are usually not significantly affected. Diabetic patients should be warned of the possibility of masked hypoglycemia.
β-adrenergic blockade may mask certain clinical signs (tachycardia) of hyperthyroidism. Abrupt withdrawal of β-blockade may precipitate a thyroid storm; therefore, patients suspected of developing thyrotoxicosis from whom Sectral therapy is to be withdrawn should be monitored closely.
Risk Of Anaphylactic Reaction
While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic.
Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Impaired Renal Or Hepatic Function
Studies on the effect of acebutolol in patients with renal insufficiency have not been performed in the U.S. Foreign published experience shows that acebutolol has been used successfully in chronic renal insufficiency. Acebutolol is excreted through the GI tract, but the active metabolite, diacetolol, is eliminated predominantly by the kidney. There is a linear relationship between renal clearance of diacetolol and creatinine clearance. Therefore, the daily dose of acebutolol should be reduced by 50% when the creatinine clearance is less than 50 mL/min and by 75% when it is less than 25 mL/min. Sectral should be used cautiously in patients with impaired hepatic function.
Sectral has been used successfully and without problems in elderly patients in the U.S. clinical trials without specific adjustment of dosage. However, elderly patients may require lower maintenance doses because the bioavailability of both Sectral and its metabolite are approximately doubled in this age group.
Clinical Laboratory Findings
Sectral®, like other β-blockers, has been associated with the development of antinuclear antibodies (ANA). In prospective clinical trials, patients receiving Sectral had a dose-dependent increase in the development of positive ANA titers, and the overall incidence was higher than that observed with propranolol. Symptoms (generally persistent arthralgias and myalgias) related to this laboratory abnormality were infrequent (less than 1% with both drugs). Symptoms and ANA titers were reversible upon discontinuation of treatment.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Chronic oral toxicity studies in rats and mice, employing dose levels as high as 300 mg/kg/day, which is equivalent to 15 times the maximum recommended (60 kg) human dose, did not indicate a carcinogenic potential for Sectral. Diacetolol, the major metabolite of Sectral in man, was without carcinogenic potential in rats when tested at doses as high as 1800 mg/kg/day. Sectral and diacetolol were also shown to be devoid of mutagenic potential in the Ames Test. Sectral, administered orally to two generations of male and female rats at doses of up to 240 mg/kg/day (equivalent to 12 times the maximum recommended therapeutic dose in a 60-kg human) and diacetolol, administered to two generations of male and female rats at doses of up to 1000 mg/kg/day, had no significant impact on reproductive performance or fertility.
Pregnancy Category B: Reproduction studies have been performed with Sectral in rats (up to 630 mg/kg/day) and rabbits (up to 135 mg/kg/day). These doses are equivalent to approximately 31.5 and 6.8 times the maximum recommended therapeutic dose in a 60-kg human, respectively. The compound was not teratogenic in either species. In the rabbit, however, doses of 135 mg/kg/day caused slight fetal growth retardation; this effect was considered to be a result of maternal toxicity, as evidenced by reduced food intake, a lowered rate of body weight gain, and mortality. Studies have also been performed in these species with diacetolol (at doses of up to 450 mg/kg/day in rabbits and up to 1800 mg/kg/day in rats). Other than a significant elevation in postimplantation loss with 450 mg/kg/day diacetolol, a level at which food consumption and body weight gain were reduced in rabbit dams and a nonstatistically significant increase in incidence of bilateral cataract in rat fetuses from dams treated with 1800 mg/kg/day diacetolol, there was no evidence of harm to the fetus. There are no adequate and well-controlled trials in pregnant women. Because animal teratology studies are not always predictive of the human response, Sectral should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Studies in humans have shown that both acebutolol and diacetolol cross the placenta. Neonates of mothers who have received acebutolol during pregnancy have reduced birth weight, decreased blood pressure, and decreased heart rate. In the newborn the elimination half-life of acebutolol was 6 to 14 hours, while the half-life of diacetolol was 24 to 30 hours for the first 24 hours after birth, followed by a half-life of 12 to 16 hours. Adequate facilities for monitoring these infants at birth should be available.
Labor And Delivery
The effect of Sectral on labor and delivery in pregnant women is unknown. Studies in animals have not shown any effect of Sectral on the usual course of labor and delivery.
Acebutolol and diacetolol also appear in breast milk with a milk:plasma ratio of 7.1 and 12.2, respectively. Use in nursing mothers is not recommended.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Sectral and other reported clinical experience is inadequate to determine whether there are differences in safety or effectiveness between patients above or below age 65.
Elderly subjects evidence greater bioavailability of acebutolol (see CLINICAL PHARMACOLOGY —Pharmacokinetics and Metabolism), presumably because of age-related reduction in first-pass metabolism and renal function. Therefore, it may be appropriate to start elderly patients at the low end of the dosing range (see DOSAGE AND ADMINISTRATION—Use in Older Patients ).This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/10/2016
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