Effects of tedisamil, atenolol and their combination on heart andrate-dependent QT interval in healthy volunteers

Aims Tedisamil is a new blocker of K⁺ currents in cardiac tissues, exerts bradycardic effects and has shown clinical efficacy in angina pectoris. Theoretically, when coadministered with a &bgr;-adrenoceptor blocker the tedisamil combination could induce dangerous bradycardia and QT interval prolongation. Therefore, the aim of this study was to evaluate the effects of tedisamil and atenolol alone and in combination, on heart rate and QT interval duration at rest and during exercise tests.
Methods The effects of tedisamil (100  mg twice daily) and atenolol (50  mg twice daily) on heart rate and QT interval duration were analysed in a three-period crossover study in healthy male volunteers.
Results This study showed that tedisamil exerted a significant ( P <0.05) bradycardic action at rest (−10 beats min⁻¹; 95% CI: -6 to -15 beats min⁻¹ ) similar to atenolol (−14 beats min⁻¹; -11 to -17) and drug combination (−9 beats min⁻¹; -6 to -12). During exercise, at the highest comparable workload, heart rate did not decrease significantly with tedisamil but decreased significantly with atenolol (−42  beats min⁻¹; -37 to -47) and combination (−47 beats min⁻¹ ; -41 to 52). Atenolol did not modify QT interval duration. Tedisamil alone and in combination with atenolol increased QT interval duration by 12% (95% CI: 7 to 17%) and 12% (8 to 16) respectively at RR=1000ms, but not at RR<700ms (combination). Tedisamil alone and in combination induced a reverse rate-dependent QT interval prolongation.
Conclusions These results indicate that the combination of tedisamil and atenolol is not associated with excessive bradycardia or excessive QT interval prolongation in healthy subjects.     

Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta2-adrenoceptor blockade

The aim of the present study was to evaluate whether metabolic responses to inhaled salbutamol may be used to measure the cardioselectivity of beta-adrenoceptor antagonists. We therefore studied the effects of oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40), and placebo (Pl) on the hypokalaemic (K) and hyperglycaemic (Glu) responses to inhaled salbutamol in five healthy subjects. Increasing doses of atenolol were associated with a progressive attenuation of delta K compared with placebo: -0.72 mmol.l-1 (Pl) vs -0.20 mmol.l-1 (A200). However, delta K with A200 was significantly different from the response with P40: +0.12 mmol.l-1. There were partial reductions in the hyperglycaemic response with the beta-adrenoceptor antagonists, although this was only significant (compared with Pl) for P40: delta Glu 1.92 mmol.l-1 (Pl) vs 0.76 mmol.l-1 (P40). These results show that beta 2-adrenoceptor blockade by atenolol is a dose-dependent phenomenon, which may be measured by the attenuation of salbutamol-induced hypokalaemia. However, beta 2-adrenoceptor blockade by atenolol 200 mg was less than that by propranolol 40 mg. The glucose response to salbutamol was only partially blocked by propranolol and may therefore not be suitable to assess beta 2-adrenoceptor antagonism.     

Lipoprotein lipids and apoproteins during beta-blocker administration: Comparison of penbutolol and atenolol

Summary Serum lipoprotein lipid and apoprotein concentrations were determined in 21 hypertensive men during administration of two beta-blockers, penbutolol or atenolol, for 6 months preceded by a 4 week placebo period. Post-heparin plasma lipoprotein lipase and hepatic lipase activities were also measured.There was a trend to an increase of triglyceride and VLDL triglyceride concentrations during penbutolol administration, but the changes were not significant. Penbutolol also increased the total cholesterol by 11% at 3 months (mainly due to increase of VLDL cholesterol), but this effect diminished at 6 months.Atenolol did not cause any significant change in the total cholesterol but increased HDL cholesterol by 7% at 1 month, the change being due to rise of the HDL₃. The HDL₃ accounted also for a significant decrease of HDL cholesterol seen in the men receiving penbutolol at 6 months. HDL₂ cholesterol as well as the LDL/HDL₂ cholesterol ratio remained unchanged in both groups.Neither drug consistently influenced the post-heparin plasma lipase activities or the serum apoprotein A or B concentrations.In contrast to an earlier study the results suggest that the clinically most important HDL subfraction, the HDL₂, remains unaffected during treatment with beta-blockers.     

Atenolol Prophylaxis in Migraine Secondary to an Arteriovenous Malformation

The migrainous syndrome secondary to a parieto-occipital arteriovenous malformation usually presents as unilateral headache with visual aura of progressive severity. We report successful prevention by atenolol of migraine with visual aura associated with an occipital vascular malformation. Effectively preventing migraine delayed specific therapeutic measures, thereby exposing the patient to the risk of an intracranial hemorrhage. The authors consider that prophylactic therapy should not be started whenever such an association is suspected.     

阿替洛尔对高血压患者血浆去甲肾上腺素和肾上腺素水平的影响

目的 :观察阿替洛尔对高血压患者血浆去甲肾上腺素、肾上腺素水平的影响。方法 :Ⅰ、Ⅱ期原发性高血压患者 10例 ,每d口服阿替洛尔 5 0mg ,连续 8d ,分别于服药前 ,服药的第 3d ,第 8d及停药后的第 2d ,用高效液相色谱法测定患者血浆去甲肾上腺素、肾上腺素水平。结果 :高血压患者血浆去甲肾上腺素水平在服药的第 3d升高 (P <0 .0 5 ) ,服药的第 8d降至正常水平 ,停药后 2d无反跳现象发生 ,血浆肾上腺素水平无显著变化。结论 :高血压患者每d口服阿替洛尔 5 0mg短期治疗对血浆去甲肾上腺素、肾上腺素水平无显著影响。     

THE EFFECT OF METOPROLOL AND ATENOLOL ON PLASMA HIGH DENSITY LIPOPROTEIN LEVELS IN MAN

1. The effects of two β-adrenoreceptor blocking drugs, metoprolol and atenolol, on plasma lipoproteins were studied in thirty-four patients using a single-blind cross-over design, with a 10-day placebo washout period between drugs. 2. Compared with placebo values, neither metoprolol nor atenolol influenced total plasma cholesterol levels, while total plasma triglycerides increased slightly. 3. Low density lipoprotein protein level remained unaltered, while high density lipoprotein (HDL) cholesterol and protein were significantly reduced by both β-adrenoreceptor blockers. 4. The ratio of total cholesterol to HDL cholesterol was increased by both drugs. 5. The data suggest that patients taking these drugs over many years may be exposing themselves to increased vascular risk, despite other anticipated benefits from such therapy.     

The efficacy and tolerability of atenolol,nifedipine, and their combination in the management of hypertension

Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily.The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components.Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately.A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.     

Long-term Effects of Captopril and Atenolol in Essential Hypertension

ABSTRACT Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n=26) or atenolol (n=24). Their mean supine diastolic blood pressure after placebo was 100–125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure <95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p<0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p<0.01 (systolic), p<0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.     

Influence of left ventricular mass regression on cardiac function in hypertensive elderly individuals

Summary A randomized, double-blind placebo controlled trial was conducted to compare the ability of verapamil and atenolol to induce regression of left ventricular mass in elderly hypertensive patients and the effects of regression on left ventricular filling, ejection fraction, and cardiac volumes. Forty-two individuals over 60 years of age were enrolled in the protocol. Eight of 21 patients assigned to atenolol and 18 to 21 assigned to verapamil achieved blood pressure control with single-agent therapy (p < 0.05). The addition of chlorthalidone resulted in blood pressure control in the three remaining assigned to verapamil and in ten of the remaining patients assigned to atenolol. In the verapamil group left ventricular mass index decreased from 104 ± 5 to 85 ± 5 g/M², while it was unchanged in the atenolol patients (109 ± 9 to 112 ± 10 g/M²). In the patients in whom the left ventricular mass regressed, the peak filling rate increased from 2.42 ± 0.2 to 3.31 ± 0.4 EDV/s, while it did not change in the patients who did not experience regression. Furthermore, ejection fraction and cardiac output were maintained in patients who had regression, both at rest and during mild upright bicycle exercise.Supported in part by a contract from the National Institute on Aging (AG 89-0809) and the Knoll Pharmaceutical Company     

荧光分光光度法测定片剂中氨酰心安

本工作建立了测定片剂中氨酰心安的荧光分光光度法。片粉经甲醇提取并稀释后即可测定荧光值(λ_(ex)278nm,λ_(em)301nm)。本品在甲醇溶液中荧光值稳定,各种辅料无干扰,方法线性良好(r=0.9999),精密度高,同次测定平均回收率100.16±1.27％;不同次测定平均回收率100.04±1.30％。按本法测定三种片剂共7个批号百分含量为98.09～100.04％。