Peripheral vascular effects of bufuralol in hypertensive and normal subjects: A comparison with propranolol and pindolol

Summary In a double-blind, single oral dose, crossover study, the effects of bufuralol (60 mg) on heart rate, blood pressure, and peripheral vascular responses were compared with those of propranolol (160 mg), pindolol (10 mg), and placebo in a group of 12 healthy volunteers.All three beta-adrenoceptor antagonists reduced exercise tachycardia, but at the doses chosen the effects of bufuralol were less than those of propranolol.Forearm blood flow was reduced by propranolol and pindolol, but not by bufuralol.The antihypertensive and peripheral vascular effects of bufuralol (30–60 mg bd) were also compared with those of propranolol (40–80 mg bd) in a double-blind crossover study in 10 patients with mild hypertension.Propranolol and bufuralol produced comparable reductions in systemic blood pressure over a two-week period, but the decreases in forearm and finger blood flow were greater with propranolol.These studies suggest that bufuralol is a beta-adrenoceptor antagonist with antihypertensive properties, and that it produces less peripheral vasoconstriction than propranolol or pindolol.     

The comparative beta-adrenoceptor blocking effects of penbutolol,atenolol and sustained-release metoprolol in healthy volunteers

Summary The effects of penbutolol (40 mg), atenolol (100 mg) and sustained-release metoprolol (metoprolol SA) (200 mg) upon heart rate (HR) and blood pressure (BP) at rest and during bicycle ergometer exercise, have been compared in 12 healthy young men using a double-blind crossover design. Measurements of each drug's effect were made before and at 3, 10 and 24 h after a single dose, and again at 24 h after the last of seven consecutive daily doses. Resting HR and systolic BP were reduced to an equivalent extent by all three drugs. During the third minute of exercise, the effects of penbutolol and atenolol upon HR and systolic BP were consistently similar and greater than those of metoprolol SA.     

Modulation of the effects of salbutamol by propranolol and atenolol

Summary Six healthy volunteers were given single oral doses of 8 mg salbutamol, 40 mg propranolol, 100 mg atenolol, 8 mg salbutamol plus 40 mg propranolol and 8 mg salbutamol plus 100 mg atenolol, in a placebo controlled study.Plasma potassium fell following salbutamol and rose following atenolol or propranolol, and the hypokalaemic effect of salbutamol was reversed more effectively by propranolol than by atenolol. Although blood glucose rose after salbutamol, it was unaffected by any of the other treatments. Lying and standing pulse rate rose after salbutamol and fell equally after either -adrenoceptor antagonist, and fell more after salbutamol plus propranolol than after salbutamol plus atenolol. Blood pressure rose after salbutamol and fell after each of the other treatments.Forty milligrams propranolol was thus more effective than 100 mg atenolol in reversing the metabolic effects of 8 mg salbutamol, and was as effective in reversing the cardiovascular effects. In cases of symptomatic salbutamol overdose, propranolol should be considered as an antidote provided the patient is not asthmatic.     

Effect of diltiazem on the pharmacokinetics of propranolol,metoprolol and atenolol

Summary The pharmacokinetic interaction between diltiazem and three -adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg.The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo.The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.     

Haemodynamic effects of atenolol,pindolol and propranolol during adrenaline infusion in man

Summary In a double blind, cross over study the haemodynamic effects of an i.v. infusion of adrenaline during concomitant administration of atenolol, pindolol, propranolol or placebo were examined in 7 healthy volunteers.During coadministration with placebo, adrenaline caused an increase in systolic blood pressure (SBP) of 26 mm Hg and a decrease in diastolic blood pressure (DBP) of 20 mm Hg. Heart rate (HR) and stroke volume (SV) were increased by about 20–30%. Total peripheral resistance (TPR) fell significantly. When the subjects were pretreated with atenolol, the adrenaline increased SBP by 16 mm Hg, the DBP did not change, HR and SV increased by 19 and 30%, and TPR fell.During concomitant administration of the non-selective betablocker pindolol, which has strong intrinsic sympathomimetic activity (ISA), adrenaline increased SBP by 11 mm Hg and DBP by 17 mm Hg. This pure pressor response led to a significant reduction in HR and SV and an increase in TPR, probably mediated through the baroreceptors. The haemodynamic response to adrenaline during coadministration of propranolol was very similar to that seen after pindolol. It is concluded that a beta₁-selective blocker interferes very little with the haemodynamic response to adrenaline, whereas it is changed to a pure pressor response during coadministration of a non-selective betablockers. ISA did not significantly modify the pressor response.     

Divergent effects of atenolol,practolol and propranolol on the peripheral metabolic changes induced by dynamic exercise in healthy men

Summary A study has been made of the effects of intravenous atenolol, practolol and propranolol on the changes induced by exhaustive dynamic physical exercise in blood pressure, heart rate and blood levels of lactate, glucose, insulin, free fatty acids and potassium. The mean endurance of dynamic exercise was reduced by all three beta-blockers, most markedly by propranolol. After all the beta-blockers heart rate showed a similar decrease during the first 60 min of exercise; atenolol caused the smallest reduction at exhaustion. All three beta-blockers lowered the systolic blood pressure during exercise; propranolol was the most active agent both during exercise and during recovery. The diastolic pressure was higher during exercise after treatment with the beta-blockers, especially propranolol. The beta-blockers did not markedly affect the elevation of blood glucose was abolished by atenolol. Plasma insulin was reduced by exercise after beta-blockade, most markedly after propranolol and practolol. All the beta-blockers were equipotent in reducing up to 60 min the exercise-induced increase in plasma free fatty acids, although at exhaustion propranolol had a significantly greater effect than atenolol or practolol. Serum potassium was higher after propranolol and atenolol than after practolol during exercise and recovery.     

Influence of hyperthyroidism on the kinetics of methimazole,propranolol, metoprolol and atenolol

Summary The kinetic profiles of oral methimazole 40mg, propranolol 80mg, metoprolol 100mg and atenolol 100mg were compared in hyperthyroid patients both during the hyper-and euthyroid states. For methimazole, neither the peak concentration (C_max), the time to reach peak concentration (t_max), the elimination half-life (t_1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p<0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t_1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.     

Comparison of labetalol,propranolol and hydralazine in hypertensive out-patients

Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.     

Effect of acute administration of propranolol and atenolol on baroreflex function in normal man

Summary The acute administration of the -adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers.Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p<0.05) to the left compared to placebo.     

Double-blind comparison of once-daily bopindolol,pindolol and atenolol in essential hypertension

Summary The efficacy of once-daily bopindolol, a nonselective-adrenoceptor blocking agent with partial agonist activity, and of pindolol and atenolol in the treatment of essential hypertension has been compared. 369 patients were investigated in a double-blind parallel-group study. The treatment period was 10 weeks. Blood pressure normalisation (diastolic BP equal to or less than 90 mmHg) was to be achieved by a stepwise increase in the dose of the test drugs, and, if required, by addition of a diuretic. Normalisation of blood pressure was achieved in 71 to 76% of the subjects, with no significant differences between bopindolol, pindolol, and atenolol. Special attention was given to evaluation of side effects by using two methods for registration of all adverse events during the study. A low incidence of drug-induced side effects was observed, with no significant difference between bopindolol, pindolol, and atenolol. There was no evidence of unsuspected adverse reactions due to bopindolol.     

Effect of metoprolol and propranolol on platelet aggregation and cAMP level in hypertensive patients

Summary Ten patients with uncomplicated moderate essential hypertension were recruited to evaluate the effect of the non-selective beta-blocker propranolol and the beta₁-selective beta-blocker metoprolol on platelet aggregation and cAMP formation. Five patients began treatment with propranolol 80 mg b. i. d. and 5 with metoprolol 100 mg b. i. d., and after 2 weeks the treatments were exchanged. ADP- and adrenaline-induced platelet aggregation and the basal level of platelet cAMP were measured at the end of each treatment period. Platelet aggregation was tested turbidometrically, using the threshold value for irreversible aggregation, and cAMP measurements were performed using a protein-binding assay.Both ADP and adrenaline thrshold values were significantly lower after propranolol than after metoprolol.The basal cAMP level was lower during propranolol than metoprolol treatment.The results indicate that platelet aggregation and basal cAMP level are influenced by beta-blockers in proportion to their affinity to different beta-adrenoceptors. This may be of value in the beta-blocker treatment of patients at high thrombotic risk.     

Effects of propranolol and tertatolol on cardiac output and regional blood flows in the rat

Tertatolol (±)-1-(tert-butylamino)-3(thiochroman-8-yloxy)-2-propanol, hydrochloride is a noncardioselective beta-adrenoceptor antagonist that is devoid of partial agonist activity. The effects of this substance on regional blood flows (RBF) in the rat were studied in comparison with those of propranolol. Rats were artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen. RBFs were assessed using radioactive microspheres of 15 ± 5 μm diameter, injected into the left ventricle. An initial injection of microspheres (⁵⁷Co) was carried out 5 min before intravenous administration of propranolol (500 μg·kg^?1), tertatolol (50 μg·kg^?1) or physiological serum. A second microsphere administration (¹¹³Tin) was performed 10 min after injection of the test substances. The animals were sacrificed 3 min after the second injection of microspheres. Neither modifications in arterial pH, pO₂, pCO₂, nor in the arterial blood pressure were observed with either propranolol or tertatolol. In contrast, a decrease in heart rate was observed (?22% with propranolol and ?14% with tertatolol). The reduction in cardiac output was 33% with propranolol and 29% with tertatolol. Propranolol reduced blood flow to the majority of structures and organs examined; such a reduction was 39% in the cerebral hemispheres, 31% in the brainstems and of greater than 20% in all the renal zones studied. With tertatolol, no significant modifications of RBF were observed in any of the cortical or medullary renal zones investigated, nor in any of the cerebral areas studied; only in several colonic areas and in the skin of the abdomen and back, were reductions in RBF observed. These results demonstrate a difference in the effects of these two substances on renal and cerebral haemodynamics.     

Comparative potency of atenolol and propranolol as beta-adrenergic blocking agents in man

Summary The comparative potency of two beta-blockers, propranolol and atenolol, in the inhibition of exercise tachycardia and isoproterenol-tachycardia has been studied in two groups of hypertensive patients, using oral doses which were increased weekly. A linear correlation was observed between the reduction in exercise tachycardia and the dose of each drug, up to a daily dose of propranolol 480 mg and atenolol 600 mg. Propranolol was slightly (0.7/1) more potent in decreasing maximal exercise tachycardia than atenolol when tested in low doses (below 100 mg); at higher doses (480 mg) no differences were found. However, atenolol was 10 times less potent than propranolol in blocking isoprenaline-induced tachycardia, which seems to be related to the cardioselectivity of atenolol.     

Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

The lipophilic beta-adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time-point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one-compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water-soluble atenolol, the AUC, C(max), Cl/(F x BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non-obese persons were clinically not relevant.     

Effects of labetalol and propranolol on blood pressure at rest and during isometric and dynamic exercise

Summary The influence of intravenous labetalol and propranolol on the blood pressure response to isometric and dynamic exercise was examined in a double blind study in eight, young, normotensive volunteers. Effects were recorded after propranolol 7.5, 15 and 30 mg i. v., and after labetalol 30, 60 and 120 mg i. v. In control experiments saline was administered. Mean blood pressure rose with successive handgrip tests following saline and propranolol, but not after labetalol, and the difference was significant. The total dose of each drug produced the same reduction in heart rate during sub-maximal bicycle exercise. The exercise-induced systolic blood pressure response did not differ between the drugs.     

Effects of atenolol and pindolol on the hypokalaemic and cardiovascular responses to adrenaline infusion

Summary To investigate if the intrinsic sympathomimetic activity of pindolol could modify its beta-blocking effects on the responses to an adrenaline infusion, 10 healthy volunteers were studied. At an interval of 1–4 weeks each subject received pindolol and atenolol in randomized order before the infusion of adrenaline 0.06 µg·kg^–1·min^–1.Pindolol prevented hypokalaemia and significantly decreased the heart rate during the adrenaline infusion. These effects were not observed after atenolol. The diastolic blood pressure was slightly increased during the infusion of adrenaline after pindolol, whereas it remained unchanged after atenolol.     

Changes in haemodynamics and left ventricular function during intravenous nifedipine infusion with and without additional propranolol in patients with coronary artery disease. A randomized,placebo controlled trial

Summary The haemodynamic effects of a combined intravenous treatment of nifedipine and propranolol in ten patients with coronary artery disease compared to a single treatment with nifedipine or placebo were investigated.Nifedipine infusion resulted in a reduction of left ventricular (LV) afterload and LV volumes with an increase in heart rate and EF and no change of the double product, coronary sinus flow, LV diastolic parameters and dp/dt_max. Addition of propranolol lowers myocardial oxygen demand by reducing heart rate and dp/dt_max together with a sustained afterload reduction with no change in LV volumes and EF.The vasodilatatory action of nifedipine pretreatment balanced the negative effects of acute beta-receptor blockade on LV function and allows the reduction of myocardial oxygen demand without a deterioration of LV function.     

温阳祛风活血法治疗早期糖尿病周围血管病变的临床研究

目的：观察温阳祛风活血法治疗早期糖尿病周围血管病变的临床疗效。方法将120例早期糖尿病周围血管病变患者随机分为治疗组60例、对照组60例。治疗过程中脱落2例。2组均采取控制血糖、血压等基础治疗。治疗组加用口服祛风活血中药汤剂、外用温阳活血中药汤剂。对照组加服己酮可可碱肠溶片。观察2组临床疗效,2组踝肱指数（ ABI）及足背动脉血流量。结果治疗组59例中,显效11例（18．6％）,有效37例（62．7％）,无效11例（18．6％）,总有效率为81.4％;对照组59例中,显效9例（15．3％）,有效28例（47．5％）,无效22例（37．3％）,总有效率为62．7％。经Ridit分析,U＝－2．198,P＝0．039,P＜0．05,说明治疗组临床疗效优于对照组。2组ABI治疗后较本组治疗前均增加（P＜0．05）,治疗组前后差值较对照组增加明显（P＜0．01）,治疗组优于对照组。足背动脉血流量治疗组治疗后较本组治疗前增加（P＜0．01）,对照组治疗前后差异无统计学意义（P＞0．05）,治疗组前后差值较对照组增加明显（P＜0．01）,治疗组优于对照组。结论温阳祛风活血法内外同治,对早期糖尿病周围血管病变有较好的临床疗效。     

Comparison of the effects of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension

Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.