Concomitant inhaled corticosteroid resensitises cardiac β2-adrenoceptors in the presence of long-acting β2-agonist therapy

被引:18
作者
Aziz, I [1 ]
McFarlane, LC [1 ]
Lipworth, BJ [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Dept Clin Pharmacol & Therapeut, Dundee DD1 9SY, Scotland
关键词
budesonide; eformoterol; salbutamol;
D O I
10.1007/s002280050478
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objective: The aim of the present study was to evaluate the effects of concomitant inhaled corticosteroid therapy on the sensitivity of cardiac beta(2)-adrenoceptors in patients receiving regular long-acting beta(2)-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 mu g 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 beta(2)-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 beta(2)-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 beta(2)-mediated adverse effects with repeated puffs of salbutamol, which might conceivably occur in the setting of acute asthma.
引用
收藏
页码:377 / 381
页数:5
相关论文
共 22 条
[1]   REFLEX VAGAL WITHDRAWAL AND THE HEMODYNAMIC-RESPONSE TO INTRAVENOUS ISOPROTERENOL IN THE PRESENCE OF BETA-ANTAGONISTS [J].
ARNOLD, JMO ;
MCDEVITT, DG .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1986, 40 (02) :199-208
[2]  
*BRIT THOR SOC, 1997, THORAX S1, V52, pS1, DOI DOI 10.1136/THX.52.2008.S1]
[3]  
ELLULMICALLEF R, 1975, LANCET, V2, P1269
[4]   BRONCHODILATOR SUBSENSITIVITY TO SALBUTAMOL AFTER TWICE-DAILY SALMETEROL IN ASTHMATIC-PATIENTS [J].
GROVE, A ;
LIPWORTH, BJ .
LANCET, 1995, 346 (8969) :201-206
[5]   PHYSIOLOGICAL REGULATION AT THE LEVEL OF MESSENGER-RNA - ANALYSIS OF STEADY-STATE LEVELS OF SPECIFIC MESSENGER-RNAS BY DNA-EXCESS SOLUTION HYBRIDIZATION [J].
HADCOCK, JR ;
WILLIAMS, DL ;
MALBON, CC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (03) :C457-C465
[6]   BETA-2-ADRENOCEPTOR DESENSITIZATION IN CULTURED HUMAN AIRWAY SMOOTH-MUSCLE [J].
HALL, IP ;
DAYKIN, K ;
WIDDOP, S .
CLINICAL SCIENCE, 1993, 84 (02) :151-157
[7]   INTRACORONARY INJECTIONS OF SALBUTAMOL DEMONSTRATE THE PRESENCE OF FUNCTIONAL BETA-2-ADRENOCEPTORS IN THE HUMAN-HEART [J].
HALL, JA ;
PETCH, MC ;
BROWN, MJ .
CIRCULATION RESEARCH, 1989, 65 (03) :546-553
[8]   beta(2)-Agonist treatment reduces beta(2)-sensitivity in alveolar macrophages despite corticosteroid treatment [J].
Hjemdahl, P ;
Zetterlund, A ;
Larsson, K .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (02) :576-581
[9]  
HOLGATE ST, 1977, LANCET, V2, P375
[10]   ASSESSMENT OF SYSTEMIC EFFECTS OF INHALED GLUCOCORTICOSTEROIDS - COMPARISON OF THE EFFECTS OF INHALED BUDESONIDE AND ORAL PREDNISOLONE ON ADRENAL-FUNCTION AND MARKERS OF BONE TURNOVER [J].
JENNINGS, BH ;
ANDERSSON, KE ;
JOHANSSON, SA .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 40 (01) :77-82