title: The psychological side effects of acebutolol and atenolol. Plasma catecholamines following exercise in hypertensives treated with pindolol: comparison with placebo and metoprolol. Hypotensive effect of oxprenolol in mild to moderate hypertension: a multicentre controlled study Effects of once daily indapamide and pindolol on blood pressure, plasma aldosterone concentration and plasma renin activity in a general practice setting Comparison of once and twice daily administration of acebutolol in hypertension. BOPINDOLOL IN THE TREATMENT OF MODERATE HYPERTENSION: A DOSE‐RESPONSE STUDY Controlled trial of acebutolol in hypertension Effects of celiprolol and simvastatin on the calculated risk of coronary heart disease (the Celisimva study) Double-blind factorial trial of prindolol and hydrochlorothiazide in hypertension. A multi-centre, placebo controlled comparative study between 200 mg and 400 mg celiprolol in patients with mild to moderate essential hypertension. [Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors]. Acebutolol in the treatment of diabetic patients with hypertension. Placebo-controlled, double-blind clinical trial of alprenolol in African hypertensive patients.
abstract: We have measured the psychological effects of acebutolol and atenolol in sixteen patients with essential hypertension . The drugs were administered in a r and omized , placebo-controlled , double-blind manner , in single daily doses of 100 mg atenolol , 400 mg acebutolol or placebo for periods of 6 weeks , each drug period being separated by a placebo period . At each 2 weekly clinic visit , a question naire design ed for assessment of state anxiety and state arousal was administered for self-completion . Arousal was significantly reduced by atenolol over the whole 6 weeks of administration . It was not affected by acebutolol .  Anxiety was significantly reduced by acebutolol but only at the first of the three 2 weekly assessment s on treatment . It was not affected by atenolol . Differences in the psychological effects of these two beta-adrenoceptor blockers are discussed in terms of their lipid solubility and haemodynamic effects This study re-examines the proposal that beta-adrenoceptor blockers with intrinsic sympathomimetic activity decrease plasma noradrenaline levels .  Thirteen patients ( aged 29 - 65 years ) with uncomplicated essential hypertension were r and omly allocated to a three period , double-blind cross-over trial . The treatment periods , each of 3 weeks duration , were composed of placebo , pindolol ( 5 mg twice daily ) and metoprolol ( 100 mg twice daily ) , dispensed in identical capsules . At the end of each treatment period , patients were exercised on a bicycle ergometer to a predetermined workload .  Blood pressure and heart rate were measured before , immediately on completion of exercise and after 10 min post-exercise rest . Blood sample s for plasma noradrenaline and adrenaline determination were also collected at these times . Blood pressures were similar during treatment with pindolol and metoprolol . As expected , heart rate was consistently lower during metoprolol treatment . Basal , pre-exercise plasma noradrenaline and adrenaline were similar at the end of each treatment period . However , the increase following exercise was significantly greater during metoprolol treatment . The post-exercise increase during pindolol treatment was indistinguishable from that in the placebo period . These findings , in a r and omised placebo-controlled study , therefore demonstrate that pindolol does not influence basal or exercise-stimulated plasma noradrenaline and adrenaline concentrations . This is best explained by a lack of effect of pindolol on the plasma clearance of catecholamines , which is impaired by beta-adrenoceptor blockers devoid of intrinsic sympathomimetic activity Summary In a multicentre , double-blind , between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension . A factorial experimental design with three factors was chosen : oxprenolol — none or daily doses of 20 , 40 , 60 and 80 mg ; dihydralazine and hydrochlorothiazide , respectively , none or 30 mg daily . Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out . Irrespective of the association with dihydralazine and /or hydrochlorothiazide , oxprenolol had a hypotensive effect linearly related to dose for st and ing systolic ( P<0.05 ) and diastolic ( P<0.01 ) pressure , and for lying diastolic ( P<0.05 ) pressure . The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol , particularly the 80 mg dose level . In general , the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure , particularly with oxprenolol 80 mg . In the latter group , the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic , respectively ; and 32.1 and 20.0 mmHg for the st and ing systolic and diastolic pressures . The drug was well tolerated ; major side effects ( heart failure and bronchospasm ) occurred in three patients Summary Sixteen patients with essential hypertension completed a double blind factorial trial comparing the effects of indapamide ( 2.5 mg daily ) and pindolol ( 10 mg daily ) on blood pressure , heart rate , plasma renin activity and plasma aldosterone concentration . There were four r and omised test phases of eight weeks each during which patients received indapamide alone , pindolol alone , indapamide plus pindolol and no active treatment ( placebo ) .  Blood pressure and heart rate were measured every two weeks . Supine mean arterial pressure fell from 117 mm Hg in the placebo phase to 111 mm Hg in the indapamide phase , 106 mm Hg in the pindolol phase and 103 mm Hg in the combined indapamide plus pindolol phase . Factorial analysis confirmed that the hypotensive effects of the two drugs were additive , without evidence of potentiation or antagonism . Indapamide caused significant reductions in plasma potassium and chloride , and increases in plasma bicarbonate and urate concentrations ; it also caused increases in plasma renin activity and aldosterone concentration . These changes are similar to those observed with thiazide diuretics 1 Thirteen hypertensive patients completed a double-blind comparison of placebo , acebutolol 200 mg twice daily and acebutolol 400 mg once daily , administered for 4 weeks in r and om order . 2 Blood pressure and heart rate were significantly reduced by both acebutolol treatments . The mean reduction of resting pressure 12 h after 200 mg twice daily ( 12/7 mmHg ) was similar to that 24 hr after 400 mg once daily ( 13/9 mmHg ) . 3 Compared to placebo , reductions in exercise heart rate and systolic pressure at 12 h after 200 mg twice daily and 24 h after 400 mg once daily were significant and similar . 4 Beta-adrenoceptor antagonism was also assessed by inhibition of the heart rate response to sublingual glyceryl trinitrate taken in the st and ing position . Both acebutolol treatments reduced the response ; the reduction after twice daily treatment ( mean 25 beats/min ) was significantly greater than after once daily treatment ( mean 19 beats/min ) . 5 There was no difference in blood pressure control between acebutolol administered once and twice daily in a total daily dose of 400 mg Summary — To determine the optimal antihypertensive dose of bopindolol , we performed a r and omized double‐blind study in parallel groups . After 15 days of placebo single‐blind , 115 hypertensive patients received daily for 28 days one of 4 doses : 0 mg ( placebo ) , 0.5 mg , 1.0 mg , 2.0 mg . The reduction of supine diastolic blood pressure ( BP ) did not exhibit the pattern of a dose‐effect relationship . The effect of 0.5 mg belonged to the plateau of the dose‐effect curve ( P=0.1 , analysis of variance ) . The reduction of heart rate ( HR ) followed a typical dose‐effect curve , with a plateau beginning with 1 mg ( P = 0.02 ) . A trend toward an increase in the incidence of side‐effects with dosage was observed ( P=0.3 ) . Thus , the optimal antihypertensive dose may be 0.5 mg or less . Previous studies not using parallel r and omized groups suggested an antihypertensive dose ranging from 2 to 4 mg . This study confirms that the dose‐effect curves of beta blockers on HR and BP are dissociated . The dose‐effect curve of HR seems unsuitable for assessing the optimal antihypertensive dose of a beta blocker Summary Acebutolol , a new cardioselective beta-adrenoceptor blocking agent , has been evaluated for the treatment of hypertension . Thirty eight previously untreated male patients with essential hypertension received placebo treatment during a 4-week run-in period , and then they were r and omly ( double-blind ) allocated either to continued placebo treatment for three 4-week periods or to treatment with acebutolol 400 , 600 and 1200 mg daily , respectively , for three 4-week periods . Blood pressure and heart rate were recorded at the end of each 4-week period . Treatment with acebutolol produced statistically significant reductions in blood pressure and heart rate as compared to the placebo regimen Objectives . The most important risk factors for coronary heart disease are hypercholesterolemia , smoking and hypertension . To find out which one – lowering cholesterol concentration or using antihypertensive treatment-is more effective in modifying the total risk , we conducted a parallel group placebo-controlled study . The goal of the study was to assess the effect of two drugs on the calculated CHD Framingham risk score in subjects with both moderate hypertension and moderate hypercholesterolemia . Design . Celiprolol for hypertension and simvastatin for cholesterol-lowering were given as monotherapy or as combination treatment . The effects of the treatments on the CHD risk scores were calculated after 3 months . A total of 112 patients were r and omized . Results . The total CHD risk decreased in simvastatin and combination groups from 26 % to 19 % and from 26 % to 17 % , respectively . Celiprolol alone decreased the risk from 25 % to 21 % , which was not statistically different from placebo . Conclusions . It can be concluded that subjects with moderate hypercholesterolemia and hypertension benefit more from lipid-lowering treatment with simvastatin than from blood pressure-lowering with beta blocker celiprolol The antihypertensive actions of the beta-adrenergic blocking agent , prindolol , and of the diuretic , hydrochlorothiazide , were analysed in a double-blind r and omized 2 X 2 factorial trial in 16 patients . There were four eight-week phases in which patients received prindolol alone , hydrochlorothiazide alone , prindolol plus hydrochlorothiazide in combination , and no treatment . Both drugs were given in fixed doses : prindolol , 10 mg three times per day ; hydrochlorothiazide , 50 mg per day . Blood pressure was measured weekly , alternately at the outpatient clinic and at home . Supine mean arterial pressure ( MAP ) in resting patients fell from 127 mm Hg in the placebo phase to 117 mm Hg with hydrochlorothiazide alone , 116 mm Hg with prindolol alone , and 111 mm Hg with the combination of prindolol and hydrochlorothiazide . ( The st and ard error of difference between treatments was + /-3 - 58 ) . A mean factorial effect of -7 mm Hg for hydrochlorothiazide ( P less than 0 - 01 ) and -8 mm Hg for prindolol ( P less than 0 - 01 ) was obtained , and the two drugs acted in an additive manner . The effects on st and ing blood pressure in resting patients were similar . No serious side effects were noted A two-centre , double-blind , placebo controlled , r and omized 3-way crossover study was undertaken to assess the efficacy , tolerability and safety of celiprolol in mild to moderate essential hypertension . A 4-week single-blind placebo run-in/screening period , during which no antihypertensive medication was given , was followed by 3 consecutive 4-week treatment periods with placebo or celiprolol ( 200 mg or 400 mg daily ) . At the end of the 4-week placebo run-in/screening period , 26 hospital out- patients with a seated mean blood pressure ( systolic/diastolic ) of 161.4/101.7 mmHg and a mean pulse rate of 75 beats/min entered the double-blind crossover phase of the study . Results showed that there was no significant difference in seated mean systolic or diastolic blood pressure between 200 mg celiprolol daily ( 149.2/92.3 mmHg ) and 400 mg celiprolol daily ( 149.1/92.5 mmHg ) . However , mean seated systolic and diastolic blood pressures were significantly ( p less than 0.05 ) lower on celiprolol than on placebo ( 157.1/98.2 mmHg ) . Neither dose of celiprolol had a significant effect on seated pulse rate . No patient was withdrawn due to an adverse event and no laboratory assessment outside the normal range was reported to be of any clinical significance . It is concluded that oral celiprolol , 200 mg or 400 mg daily , is effective and well tolerated for controlling mild to moderate essential hypertension . Since both doses had very similar effects on blood pressure there is no advantage in this group of patients for the 400 mg daily dose of celiprolol BACKGROUND AND OBJECTIVE In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function . Treatment regimens which reduce proteinuria and hypertension improve prognosis . The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest . PATIENTS AND METHODS The studied cohort consisted of 11 patients with CGN , hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks , doubly blinded and r and omized according to a " Latin-square design " : Celiprolol ( beta-1-antagonist , beta-2-agonist , 200 mg/d ) , Atenolol ( selective beta-1-antagonist , 50 mg/d ) , Ramipril ( ACE-inhibitor , 2.5 mg/d ) and placebo . There was a two-week wash-out phase between each of the four treatment phases . At the end of each treatment phase glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured by inulin and para-amino-hippuric acid ( PAH ) clearance . Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase . During this period blood pressures were measured with a continuous 24-hour blood pressure monitor . RESULTS Mean arterial blood pressure ( MAP ) was significantly reduced , compared with placebo , by all three antihypertensives ( 108 + /- 9 mm Hg with placebo , 98 + /- 12 mg Hg with atenolol , 101 + /- 11 mm Hg with celiprolol and 98 + /- 8 mm Hg with ramipril ; P < 0.01 ) . Celiprolol produced a significant rise In ERPF ( 322 + /- 109 ml/min with placebo , 391 + /- 110 ml/min with celiprolol : P < 0.05 ) . GFR was slightly , but not significantly , reduced by celiprolol and atenolol .  Filtration fraction remained unchanged with atenolol and celiprolol , while it was slightly , but not significantly , reduced with ramipril . Compared with the placebo , all three drugs significantly reduced proteinuria ( P < 0.05 ) : 1.8 + /- 1.3 g/24 h with placebo , 1.2 + /- 1.2 g/24 h with atenolol , 1.2 + /- 1.1 g/24 h with celiprolol and 1.4 + /- 1.4 g/24 h with ramipril . CONCLUSION These data indicate that , in addition to ACE inhibitors , the new generation of beta-receptor blockers in particular , because of their vasodilator action , favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension A double-blind , parallel group comparison study was carried out in 20 diabetic patients with mild to moderate hypertension to assess the effectiveness and tolerance of acebutolol compared with placebo . After a 4-week wash-out period on placebo , patients received either 400 mg acebutolol or placebo once daily for 12 weeks and then placebo for a further 4 weeks . The results showed that acebutolol was more effective than placebo in lowering raised blood pressure in these patients . No deterioration in diabetic control occurred during the study and no significant side-effects of the drug were observed compared with placebo . In particular , the previously described side-effects of beta-blocker therapy in diabetic patients were not observed as a clinical problem in this study A placebo-controlled , double-blind clinical trial of alprenolol was carried out in 20 hypertensive Africans . The active drug and placebo were each administered for 8 weeks using a crossover design . Alprenolol was given in the form of a slow-release tablet preparation at a dosage of 200 mg twice daily . Four patients were withdrawn from the study either because of side-effects ( 2 patients ) or non-compliance  ( 2 patients ) . The mean reduction in blood pressure obtained in the 16 patients who completed the trial was less than that usually reported in Caucasians
target: Pindolol , celiprolol and alprenolol  lowered SBP and DBP compared to placebo .
  Acebutolol  lowered SBP but there was no clear evidence that it lowered DBP .
  There was no clear evidence that pindolol and  oxprenolol lowered SBP or DBP .
  Higher dose partial agonists did not appear to provide additional BP lowering effects compared to lower dose .
  There was no evidence of a greater effect at doses higher than the initial doses .
  Based on the indirect comparison of the results in this review and two Cochrane review s on angiotensin-converting-enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) , which also used similar inclusion criteria as this review , the BP lowering effect appeared to be less than the effect in patients with mild to moderate elevated BP who were taking ACE inhibitors  and ARBs based on an indirect comparison .
  Withdrawals due to adverse effects were only reported in one trial so it is impossible to assess the harm of these drugs
background: BACKGROUND Partial agonists are a subclass of beta blockers used to treat hypertension in many countries .
  Partial agonist act by stimulating beta receptors when they are quiescent and blocking beta receptors when they are active .
  The blood pressure ( BP ) lowering effect of partial agonist beta blockers has not been quantified .
  OBJECTIVES To quantify the dose-related effects of various partial agonists beta blockers on systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and heart rate versus placebo in patients with primary hypertension .