Effects Of Acebutolol Research Articles

Trough: peak ratio in the assessment of the hypotensive effect of acebutolol

Trough: peak ratio in the assessment of the hypotensive effect of acebutolol

Evidence for a dual effect of acebutolol, a beta blocker, on the mouse humoral immune response.

Acebutolol induces transient polyclonal B cell activation in C57B1/6 mice but down-modulates the spontaneous polyclonal activation of NZBxNZW lupus mice. The immunomodulatory effects of this beta-blocker were studied in C57l/6 mice injected with LPS or immunized with sheep red blood cells. The effect of acebutolol on the polyclonal activation of lymphocytes induced by LPS was also investigated in heterozygous and nu/nu C57BL/6 mice. Finally, the direct effect of acebutolol on spleen cells was studied in vitro. Acebutolol treatment for 15 days (50mg/kg/day) inhibited the polyclonal activation of lymphocytes induced by LPS in C57BL/6 and in C57BI/6 nu/nu mice, but increased the humoral response to sheep red blood cells in C57Bl/6 mice. Moreover, spleen cells from C57Bl/6 mice treated for 15 days with acebutolol showed an increased number of CD5+ and CD4+ lymphocytes, as well as an increased reactivity to concanavalin A but not to LPS. In vitro, acebutolol at 10(-5)-10(-7) M induced an increased reactivity of spleen cells from naive mice to concanavalin A, whereas it did not affect the B cell responsiveness to LPS. These results indicate that acebutolol modulates both T-cells and non T-cells in the immune system.

Differences in the Haemodynamic Effects of Acebutolol and Propranolol during Long Term Treatment of Patients with Hypertension

The aim of this study was to compare the haemodynamic effects of acebutolol, a β1-selective adrenoceptor blocker with intrinsic sympathomimetic activity, and propranolol, a nonselective β-adrenoceptor blocker without intrinsic sympathomimetic activity. 44 males aged 35 to 59 (mean 49.7 ± 1.0) years with mild to moderate arterial hypertension (diastolic blood pressure 95 to 114mm Hg) without severe concomitant diseases requiring medication, and without contraindications to β-adrenoceptor blockade, were included in this double-blind randomised parallel group study. It was shown that during 12 weeks’ treatment the magnitude and duration of the antihypertensive effect of acebutolol 400 or 800mg daily did not differ from that of propranolol 80 or 160mg daily. However, there was a trend towards more patients achieving a full or partial antihypertensive effect with acebutolol than propranolol. Moreover, bradycardia was more pronounced with propranolol. The antihypertensive effect of acebutolol was observed after 2 weeks and maintained throughout all 12 weeks of treatment. Unlike propranolol, acebutolol did not cause such unwanted haemodynamic effects as decreased cardiac output and increased total peripheral resistance. Acebutolol was well tolerated.

Chronic use of acebutolol in the treatment of cardiac arrhythmias

Among the present-day controversies in cardiology is the challenge of safely treating cardiac arrhythmias. Many factors involved in the decision to initiate treatment remain to be clearly defined. In addition, the choice of antiarrythmic drugs, although expanding, includes a number of poorly-tolerated cellular toxins. A recent review of the literature confined to double-blind prospective studies enrolling over 100 post-myocardial infarction patients reveals that in 6 of 11 surveyed studies survival was better in the placebo-treated gr0up.l One recent study2 identified an increased risk of sudden death from two antiarrythmic agents even though arrhythmias had initially been suppressed. Antiarrythmic agents have also been shown to increase the defibrillation threshold, raising the energy required to terminate ventricular fibrillation.3 Thus the question remains: Is there any benefit to be derived from treating an arrythmia and, if so, is it justified in the presence of a risk of serious toxicity ?4 The answer varies depending on the type of arrhythmia, the antiarrhythmic agent(s) prescribed, and the concomitant medications. Two major considerations in deciding to initiate treatment of cardiac arrhythmias are the ability of the agent to suppress the arrhythmia and to improve survival. Except for P-blockers, as observed in the @-Blocker Heart Attack Trial (BHAT),5 Acebutelol et Prevention Secondaire de 1’Infarctus (APSI),6 and other studies,l, 8 treatment with antiarrhythmic drugs has not been shown to reduce the risk for cardiac death.l, g Hence a review of the antiarrhythmic effects of acebutolol, a cardioselective P-blocker with intrinsic sympathomimetic activity that has been proven efficacious in both suppression of arrhythmia and improvement of survival in high-risk post-MI

Beneficial effect of acebutolol on post-hypoxic recovery of cardiac contractility

Beneficial effect of acebutolol on post-hypoxic recovery of cardiac contractility

Polyclonal Stimulation of Lymphocytes Induced by Beta Blockers in the Mouse: Influences of Age, Sex and Strain

The immune effects of acebutolol, a beta-blocker, are investigated in various strains of mice. In 6-12 weeks old C57Bl/6 female mice, an increase in the number of immunoglobulin secreting cells is observed only at the age of 9 weeks. At that age, such an effect is seen neither in C57Bl/6 male mice nor in female mice from 6 other strains including OF1 outbred mice. An increase in anti-trinitrophenol plaque forming cells is found in 9 week old C57Bl/6, Balb/c and CBA female mice.

Acute and Long-Term Effects of Acebutolol on Systemic and Renal Hemodynamics, Body Fluid Volumes, Catecholamines, Active Renin, Aldosterone, and Lymphocyte β-Adrenoceptor Density

Acebutolol is a relatively new beta-adrenoceptor blocking antagonist, possessing both beta 1-adrenoceptor selectivity and partial agonist activity (PAA). Its acute (24 h, 400 mg, twice daily) and long-term effects (3 weeks) on systemic and renal hemodynamics, body fluid volumes, hormones, and beta-adrenoceptor density on lymphocytes were studied in a single-blind placebo-controlled trial, in 10 hypertensive patients. The initial response to acebutolol (1-2 h) was a fall in heart rate (HR) (-9.6 +/- 2.7%), cardiac output (-16.0 +/- 3%), and stroke volume (SV) (-10.7 +/- 0.2%), and an increase in systemic vascular resistance (SVR) (18.0 +/- 3.9%). Mean arterial pressure (MAP) began to fall 2-3 h after dosing in parallel with a decrease in SVR. At the end of the acute study, MAP and SVR were decreased by 18.1 +/- 2.7% and 15.6 +/- 5.6%, respectively. By that time, HR and SV had returned to control values despite blockade of beta-adrenoceptors. After 3 weeks of treatment (mean dose of acebutolol 480 mg twice daily), the fall in MAP was 10.1 +/- 2.7% and HR was decreased by 13.0 +/- 2.3%. Renal blood flow and glomerular filtration rate did not change. Acute and long-term treatment had no effect on the density of lymphocyte-membrane beta-adrenoceptors. This could be explained by acebutolol's beta 1 selectivity or, alternatively, this could be due to the drug's PAA.

Atrial Natriuretic Peptide during Exercise in Patients with Coronary Heart Disease before and after Single Dose Atenolol and Acebutolol

Plasma atrial natriuretic peptide (ANP) was measured during dynamic exercise in 10 patients with coronary heart disease before and after single dose atenolol 50 mg and acebutolol 200 mg, respectively. Systolic blood pressure, heart rate and the rate-pressure product increased during exercise before and after beta-blockade, but levels were lower after beta-blockade. Plasma ANP levels at rest were unchanged after atenolol, but rose after acebutolol (p less than 0.01). During exercise plasma ANP increased significantly both before and after beta-blockade, but plasma ANP levels were higher after acebutolol at all workloads (p less than 0.05), whereas plasma ANP levels after atenolol were higher at 125 W exclusively (p less than 0.05). The augmented ANP levels during exercise after beta-blockade probably reflect catecholamine-stimulated ANP release, whereas the elevated plasma ANP levels after acebutolol at rest might be a beta-adrenoceptor-mediated ANP release due to the intrinsic sympathomimetic effect of acebutolol.

The side effects of acebutolol

The side effects of acebutolol

Effect of acebutolol on left ventricular performance

The effect of acebutolol on left ventricular performance was examined by various noninvasive means in three studies. M-mode echocardiographic measurements were made in 21 patients with coronary artery disease who were receiving placebo, acebutolol, and propranolol in a double-blind, randomized, crossover study. In these patients with normal or near-normal resting left ventricular function, neither drug induced depression of left ventricular function. In 26 patients with chronic angina pectoris receiving acebutolol under double-blind, placebo-controlled conditions, gated (equilibrium) myocardial blood pool imaging using red blood cells labeled with technetium 99m showed acebutolol to have no clinically significant negative effect on left ventricular performance at rest or during supine bicycle exercise. Acebutolol at effective antianginal doses modestly improved resting global and regional myocardial function. In 13 patients with stable angina pectoris, single-pass studies of left ventricular function with indium 113 under double-blind, placebo-controlled conditions similarly showed acebutolol to have no clinically significant negative inotropic effects. In conclusion, acebutolol is safe for use in patients with coronary disease and a wide range of ejection fractions but, as with all beta blockers, should be used cautiously in patients with markedly reduced resting left ventricular function.

Role of beta-adrenoreceptor antagonism in the prevention of reperfusion ventricular arrhythmias: Effects of acebutolol, atenolol, and d-propranolol on isolated working rat hearts subject to myocardial ischemia and reperfusion

The role of catecholamines in the genesis of ventricular arrhythmias during the reperfusion period following coronary occlusion remains incompletely understood. An isolated rat heart preparation, free from the influence of autonomic innervation or of circulating catecholamines, was used to assess the effects of beta-adrenoceptor blockade. The hearts were prelabeled with tritiated norepinephrine (NE 3H), and the total radioactivity and that in NE 3H were measured in the effluent coronary flow. The left main coronary artery was ligated for 10 minutes after which reperfusion followed. The liberation of NE 3H and the development of ventricular tachycardia and fibrillation were monitored throughout. The cardioselective beta-antagonist agent, acebutolol, in a high concentration (1.1 × 10 −4M), had good beta-antagonist effect in response to the added isoproterenol (10 −5M); this concentration of acebutolol also suppressed sustained reperfusion ventricular arrhythmias but unexpectedly increased the release of NE 3H. Atenolol, another cardioselective agent, did not prevent reperfusion ventricular arrhythmias even in a high concentration of 40 mg/L (1.5 × 10 −4M). The d-isomer of propranolol, with poorer beta-antagonist properties than the I-isomer, prevented such ventricular arrhythmias in a concentration of 1.3 × 10 −5M, which was low when compared to that of atenolol. It is proposed that the beta-antagonist activity of the compounds tested could not explain the inhibition of reperfusion ventricular arrhythmias and that another quality such as membrane-stabilizing activity may be involved.

Effect of acebutolol on left ventricular hemodynamics and anatomy in systemic hypertension

In 18 patients with mild or moderate essential hypertension who responded favorably to acebutolol antihypertensive therapy, echocardiography (echo) was performed in the basal condition and after 6 and 12 months of follow-up. Acebutolol induced a significant decrease in blood pressure (BP), from a basal value of 167 ± 3 105 ± 2 mm Hg to 138 ± 5 90 ± 2 mm Hg after 6 months (p < 0.01) and to 134 ± 3 91 ± 3 mm Hg after 1 year (p < 0.01) and in heart rate, from 75 ± 3 to 63 ± 2 beats/min after 6 months (p < 0.01) and to 63 ± 2 beats/min after 1 year (p < 0.01). The decrease in BP was achieved through a decrease in cardiac output from 6.3 ± 0.28 to 5.3 ± 0.25 liters/min after 6 months (p < 0.05) and to 5.32 ± 0.2 liters/min after 1 year (p < 0.05), which resulted from a reduction in heart rate; stroke volume did not show significant change during the treatment and left ventricular (LV) performance was improved. There was a parallel decrease in LV posterior wall and ventricular septal thicknesses and estimated LV mass. In patients with LV hypertrophy, the change in mass was significantly correlated with the change in heart rate both after 6 and 12 months of therapy (r = 0.6234, p < 0.05 and r = 0.7121, p < 0.05 after 6 and 12 months, respectively).

46 Antihypertensive Effect of Acebutolol and Nifedipine at Rest and During Dynamic and Isometric Stress-testing in Hypertensive Subjects

46 Antihypertensive Effect of Acebutolol and Nifedipine at Rest and During Dynamic and Isometric Stress-testing in Hypertensive Subjects

The effect of acebutolol on plasma lipids, blood glucose and serum insulin levels.

The effect on plasma lipids of acebutolol given orally over a 6-month period to 18 patients with essential hypertension was studied. There were no significant changes in the concentrations of plasma total cholesterol, LDL cholesterol, VLDL cholesterol and triglycerides during treatment. The level of HDL cholesterol decreased slightly but not significantly during treatment. Plasma free fatty acids decreased significantly (p less than 0.05) during treatment with acebutolol. During an oral glucose tolerance test, blood glucose values were elevated after acebutolol therapy at 60 (p less than 0.05) and 120 min (p less than 0.05). No impairment of insulin release was observed after acebutolol therapy.

Platelet activation after adrenergic stimulation in hypertensive patients: effects of acebutolol.

In 12 patients with arterial hypertension (stages I and II according to WHO), adrenergic stimulation was induced by the immersion of a hand in ice water for 2 min. Blood samples were withdrawn before, at the end of, and 15 min after the cold application: the experiment was repeated 2 h after the ingestion of 200 mg acebutolol, a selective betablocking agent. The following assays were performed: serum nonesterified fatty acid (NEFA), plasma beta-thromboglobulin (BTG) and PF4 with specific radioimmunoassays; thromboxane B2 (TXB2) in plasma was also estimated with radioimmunoassay, platelet sensitivity to exogenous prostacyclin; furthermore, the thrombin-induced thromboxane production before and after acebutolol ingestion as well as serum TXB2-levels were measured. The blood pressure and the heart rate were also monitored. After cold stimulation, a significant increase of NEFA, BTG, and plasma TXB2 was observed, which was still discernible 15 min after the application of cold. After acebutolol, the cold treatment led to a lower increase of blood pressure with a reduction of the heart rate, as well as to a diminished release of BTG, PF4 and TXB2 no changes in the reduced platelet sensitivity to prostacyclin were noticed.

Effect of acebutolol on plasma catecholamine concentrations in anesthetized dogs with ouabain-induced arrhythmias and its direct actions in vitro on the adrenal medulla.

We have performed studies on blood hormone dynamics following intravenous administration of acebutolol, a newly synthesized beta-blocker, and its direct action on the adrenal medulla in vitro. Intravenous injection of acebutolol into anesthetized dogs almost doubled the plasma adrenaline and noradrenaline concentrations within 5 to 15 minutes, while renin activity was reduced to approximately two-thirds of the pre-administration level. When arrhythmia was induced in dogs with ouabain, the plasma adrenaline and noradrenaline levels increased to 220 +/- 109 and 392 +/- 84 pg/ml, respectively, from the basal levels of 44 +/- 24 and 140 +/- 43 pg/ml. The restoration of sinus rhythm following the administration of acebutolol was accompanied by a further increase in the plasma adrenaline and noradrenaline levels to 797 +/- 364 and 1226 +/- 263 pg/ml, respectively. A perifusion experiment indicated that acebutolol directly accelerated catecholamine release from the adrenal medulla in pigs.

Effects of Acebutolol on Paroxysmal Atrioventricular Reentrant Tachycardia in Patients with Manifest or Concealed Accessory Pathways

Electrophysiologic studies before and after administration of 50 mg of intravenous (IV) acebutolol were performed in 20 patients. Four of the 20 had persistent preexcitation, two had intermittent preexcitation, and 14 had a concealed retrogradely conducting accessory pathway (AP). Acebutolol depressed anterograde AP conduction with loss of preexcitation in one patient and increased the effective refractory period of AP in the remaining three; in most, it depressed anterograde normal pathway conduction. The longest atrial paced cycle length producing atrioventricular (AV) nodal block increased from 290 +/- 7 to 39 +/- 6 msec (mean +/- SEM) after acebutolol (p less than 0.01). Acebutolol had no significant effect on retrograde AP conduction. Sustained AV reentrant tachycardia was inducible in all 20 patients before acebutolol and in 19 after acebutolol. The cycle length of tachycardia increased from 323 +/- 8 to 352 +/- 8 msec after acebutolol (p less than 0.01), reflecting an increment of A-H interval from 148 +/- 8 to 174 +/- 9 msec (p less than 0.01). Electrophysiologic studies were reported after 800 mg of oral acebutolol given in four divided doses at six-hour intervals in eight patients. The results were comparable to those of IV acebutolol. Thus, acebutolol depresses AV nodal conduction and slows the rate of AV reentrant tachycardia, but is generally ineffective in inhibiting the induction of sustained tachycardia. It occasionally depresses anterograde AP conduction.

The effect of acebutolol and propranolol on the hypoglycaemic action of glibenclamide.

1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose levels and both acebutolol and propranolol, at therapeutic doses, were found to modify this action significantly. 3 The effect of acebutolol was slightly less than that of propranolol. The difference was not statistically significant. 4 The modes of action of sulphonylureas are reviewed and it is suggested that beta-adrenoceptor blockers may modify their effect on insulin release. This appears to be a drug interaction rather than an effect of beta-adrenoceptor blockade on glucose tolerance.

Variability of spontaneous and exercise-induced ventricular arrhythmias in the absence and presence of treatment with acebutolol or quinidine

A randomized double-blind crossover trial was undertaken in 20 volunteers to evaluate the effects of acebutolol and sustained release quinidine sulfate. The patients had an average of 10 or more premature ventricular complexes/hour on two 24 hour electrocardiographic recordings, or 10 or more/min during two cycle stress tests, or any number of complex forms of ventricular ectopic activity on either test. The 24 hour recordings yielded greater detection of complex forms than did stress tests and manifested similar relative variability in frequency of ventricular ectopic beats. The extent of variability from hour to hour within the 24 hour monitoring periods tended to have an increasing relation with frequency of ectopic beat activity regardless of the presence or absence of treatment. Within-patient variability among periods with equivalent treatment status also tended to have such an increasing relation with frequency of ectopic beat activity. About 35 percent of the variation was among subjects, 20 percent among months within subjects, 20 percent among days in months and 25 percent among hours in days. Acebutolol, 300 mg three times daily, produced effective beta receptor blockade and was better tolerated than sustained release quinidine sulfate in identical doses and had equal suppressant effects. The results of the variability studies provide guidelines for the design of adequate clinical trials testing suppressant interventions.

The effect of acebutolol on cardiac arrhythmias in patients with chronic coronary artery disease

The effect of the beta-blocking drug acebutolol on the severity of cardiac arrhythmias and the incidence of exercise-induced arrhythmias was studied in 15 patients with chronic coronary artery disease using ambulatory Holter monitoring and bicycle ergometry. We found a significantly lower grading of arrhythmias both on long-term ECGs and during and after exercise. Furthermore, there was a significant decrease in the incidence of VPBs during and after exercise (18.15 ± 7.7 on placebo vs. 3.46 ± 1.7 on acebutolol). It is concluded that acebutolol favorably influences the incidence and severity of ventricular arrhythmias in patients with chronic coronary artery disease.