Effects of terbutaline and atenolol on large and small airways in asthmatic patients

Abstract

In order to localize the main site of action of the beta 2-adrenoceptor selective agonist terbutaline and the beta 1-adrenoceptor selective antagonist atenolol in the airways of asthmatic patients, we compared the effects of these drugs on maximal expiratory flow-volume (MEFV) curves when breathing air and when breathing a helium-oxygen (HeO2) mixture. To investigate whether a shift in localization of the bronchodilator effect occurs when terbutaline is inhaled repeatedly, dose-response curves with terbutaline were performed for parameters derived from MEFV curves when breathing air and for density dependence of expiratory airflow. By measurement of MEFV curves when the patients were breathing air alone, it was not possible to determine whether there is a difference in the bronchoconstrictor effect of atenolol between large and small airways. Inhalation of terbutaline to a cumulative dose of 2.0 mg induced a stepwise improvement in expiratory airflow parameters for large and small airways function when breathing air. Doubling the dose of inhaled terbutaline to 4 mg did not result in any further improvement of lung function. Neither atenolol nor terbutaline induced significant mean changes in density dependence of expiratory airflow. This was partly due to large inter- and intra-individual variations of this parameter. Another possibility is that atenolol and terbutaline effect large and small airways function equally.

Bronchodilator response in adult patients with cystic fibrosis: effects on large and small airways

“…In the present study.-terbutaline induced a significant and consistent increase in density dependence in adult CF patients. Therefore, it seems that terbutaline mainly caused dilatation of the peripheral airways, whereas ipratropium bromide presumably dilates large and small airways equally, leaving density dependence relatively unchanged [6].…”

“…Several authors found different localizations of the effects of bronchodilators on normal subjects and patients with asthma [6,[9][10][11]. The most consistent finding was that beta-sympathicomimetics predominantly cause dilatation of small airways, especially when these contribute to a large extent to total airway resistance [6,10,11].…”

“…The He-0 2 mixture was washed in during 1 min tidal breathing in which the patient was asked to inhale three slow vital capacities [9,11]. Density dependence was expressed as delta-MEF, 0 = {MEF, 0 (He-0 1 ) -MEF, 0 (AIR)} I MEF, 0 (AIR) x 100% [6].…”

“…When breathing a low density gas mixture like heliox (80% helium and 20% oxygen) the density dependence expressed as delta maximal expiratory flow when 50% total lung capacity remains in the lung (MEF 5 ,) can be assessed. A delta MEF 0 of <20% is compatible with obstruct ion in perip~eral airways [5][6][7][8]. When a bronchodilator predominantly dilates small airways, the central turbulent airflow pattern will contribute more to overall resistance and del t a MEF 50 increases.…”

“…When a bronchodilator predominantly dilates small airways, the central turbulent airflow pattern will contribute more to overall resistance and del t a MEF 50 increases. Effects of be t aadrenoreceptor agonists and muscarinic receptor antagonists on large and small airways have been determined in normal subjects and patients with asthma by assessing this density-dependence [6,[9][10][11].…”