Abstract
Objective: The aim of the present study was to evaluate the effects of concomitant inhaled corticosteroid therapy on the sensitivity of cardiac β2-adrenoceptors in patients receiving regular long-acting β2-agonists.
Methods: Twelve healthy subjects (6 female), mean age 29 years, were randomised in a double-blind cross-over study to receive either inhaled placebo or inhaled budesonide 1.2 mg twice daily, each for 7 days, with a minimum of 7 days washout period between the two treatments. Patients also received concomitant treatment with inhaled eformoterol 24 μg twice daily during each of the 2 treatment periods. The patients attended the laboratory during both treatment periods at 0730 hours, when a dose-response curve for systemic β2-adrenoceptor responses to inhaled salbutamol (0.8–3.2 mg) was constructed before and after completing 7 days of each treatment. Early morning (0800 hours) plasma cortisol was also evaluated as a marker of systemic glucocorticoid activity.
Results: There was a significant fall in 0800 hours plasma cortisol induced by budesonide comparing pre- and post- values (407 vs 322 nmol · l−1, but not with placebo. There were no differences in the response to salbutamol prior to treatment when comparing eformoterol with placebo versus eformoterol with budesonide. Comparing before and after within-treatment heart rate response, there was a significant reduction in peak salbutamol response with eformoterol and placebo, which was partially reversed by eformoterol and budesonide. For between-treatment comparisons after eformoterol treatment, the heart rate was significantly higher in the presence of budesonide in comparison with placebo for peak salbutamol response (change from baseline), i.e. 24.2 vs 34.7 beats · min−1. There was, however, no significant difference in the peak delta potassium response to salbutamol after eformoterol treatment when comparing budesonide with placebo (−0.39 vs −0.48 mmol · l−1).
Conclusion: Concomitant therapy with inhaled budesonide resensitised the cardiac β2-adrenoceptor response to salbutamol in subjects who were receiving regular twice-daily eformoterol. This may be of clinical relevance in terms of the propensity for systemic β2-mediated adverse effects with repeated puffs of salbutamol, which might conceivably occur in the setting of acute asthma.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 28 October 1997 / Accepted in revised form: 11 March 1998
Rights and permissions
About this article
Cite this article
Aziz, I., McFarlane, L. & Lipworth, B. Concomitant inhaled corticosteroid resensitises cardiac β2-adrenoceptors in the presence of long-acting β2-agonist therapy. E J Clin Pharmacol 54, 377–381 (1998). https://doi.org/10.1007/s002280050478
Issue Date:
DOI: https://doi.org/10.1007/s002280050478