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正常受试者吸入非诺特罗和沙丁胺醇后心脏β1/β2相对活性的单剂量比较。

Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

作者信息

Newnham D M, Wheeldon N M, Lipworth B J, McDevitt D G

机构信息

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee.

出版信息

Thorax. 1993 Jun;48(6):656-8. doi: 10.1136/thx.48.6.656.

Abstract

BACKGROUND

The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses.

METHODS

Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline.

RESULTS

At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses.

CONCLUSIONS

These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses.

摘要

背景

本研究的目的是使用β1选择性拮抗剂阿替洛尔比较非诺特罗和沙丁胺醇对心脏β1和β2受体的剂量相关效应,以剖析相对的β1/β2介导的反应。

方法

14名正常志愿者被随机分为两组,一组接受25mg阿替洛尔预处理,另一组接受安慰剂预处理,随后吸入等重量剂量的非诺特罗或沙丁胺醇(累积剂量分别为1mg和4mg)。在吸入每剂β2激动剂30分钟后进行测量。数值(均值和95%可信区间)表示为相对于基线的变化。

结果

4mg非诺特罗导致的血清钾下降和震颤增加与沙丁胺醇相当。安慰剂后4mg非诺特罗使心率(次/分钟)平均(95%可信区间)增加47(41 - 53),阿替洛尔后增加34(28 - 40);沙丁胺醇在安慰剂后增加46(40 - 52),阿替洛尔后增加30(24 - 36)。4mg剂量阿替洛尔后,非诺特罗的变力反应(每搏输出距离)为5.0(3.9 - 6.1)cm,沙丁胺醇为4.7(3.5 - 5.9)cm。安慰剂或阿替洛尔处理后,两种药物在心率或每搏输出距离反应方面均无显著差异。此外,非诺特罗和沙丁胺醇在两种剂量下的心电图效应(Q-Tc和T波)相当。

结论

这些结果表明,高于常规剂量给药时,非诺特罗和沙丁胺醇对心脏β1或β2受体的变时或变力活性没有差异。

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