Sjöswärd Kerstin Naidu, Josefsson Martin, Ahlner Johan, Schmekel Birgitta
Institute of Medicine and Care, Faculty of Health, University of Linköping, Sweden.
Clin Physiol Funct Imaging. 2003 Jan;23(1):14-20. doi: 10.1046/j.1475-097x.2003.00462.x.
Racemic salbutamol, a beta2-adrenoceptor agonist used for dilatation of airways, has recently been shown to induce lessened relaxation of bronchial smooth muscle and partial loss of bronchoprotection, seen as increased hyperresponsiveness, after regular treatment. The racemate undergoes stereo-selective disposition, giving higher plasma levels of S-salbutamol than that of bronchodilating R-salbutamol, thus raising S : R ratios after repeated administration. Our aim was to evaluate whether increased bronchial hyperresponsiveness (BHR) could be found even after 1 day of repeated salbutamol inhalations, with beta2-receptor-induced bronchial smooth muscle relaxation remaining and whether this would be associated with plasma levels of either enantiomer. Fifteen patients with stable asthma, aged 19-54 years, were included in a randomized, cross-over study. An indirect bronchial challenge method was used [voluntary isocapnic hyperventilation of cold air (IHCA)], and airway condition tested by means of impulse oscillometry. Racemic salbutamol was inhaled three times during a 6-h period. IHCA was performed and plasma concentrations of enantiomers were measured 4 h after the last dose. Tests were also performed without preceding drug treatment. beta2-Agonist-produced bronchial dilatation and protection persisted in the majority of the 15 patients 4 h after repeated inhalations of salbutamol during 1 day. In only two of the 15 patients we could trace increased BHR after salbutamol. Neither dilatation nor protection could be linked to plasma levels of either R- or S-salbutamol. The underlying mechanisms of BHR remain unknown and are dissociated from beta2-receptor-mediated dilatation.
消旋沙丁胺醇是一种用于扩张气道的β2肾上腺素能受体激动剂，最近有研究表明，在常规治疗后，它会导致支气管平滑肌舒张减弱和支气管保护作用部分丧失，表现为高反应性增加。消旋体具有立体选择性分布，使得S-沙丁胺醇的血浆水平高于具有支气管舒张作用的R-沙丁胺醇，因此在重复给药后S:R比值升高。我们的目的是评估即使在重复吸入沙丁胺醇1天后是否能发现支气管高反应性（BHR）增加，同时β2受体介导的支气管平滑肌舒张是否仍然存在，以及这是否与两种对映体的血浆水平有关。15名年龄在19 - 54岁的稳定期哮喘患者被纳入一项随机交叉研究。采用间接支气管激发方法[冷空气等容过度通气（IHCA）]，并通过脉冲振荡法测试气道状况。在6小时内吸入消旋沙丁胺醇3次。在最后一剂后4小时进行IHCA并测量对映体的血浆浓度。在未进行药物预处理的情况下也进行了测试。在15名患者中，大多数患者在1天内重复吸入沙丁胺醇后4小时，β2激动剂产生的支气管舒张和保护作用仍然存在。在15名患者中只有2名在使用沙丁胺醇后出现BHR增加。舒张和保护作用均与R-或S-沙丁胺醇的血浆水平无关。BHR的潜在机制仍然未知，并且与β2受体介导的舒张作用无关。
