Tolerance with beta 2-adrenoceptor agonists: time for reappraisal

Abstract

1. In spite of the widespread use of beta 2-adrenoceptor agonists in the treatment of asthma controversy continues regarding their possible role in increasing asthma mortality and morbidity. There is however no evidence available to suggest that tolerance to the bronchodilator or anti-bronchoconstrictor effects of these drugs is responsible for the deleterious effects reported with the regular use of bronchodilators. 2. There is no conclusive evidence to suggest that tolerance develops to the bronchodilator effects of short-acting beta 2-adrenoceptor agonists. Tolerance does however appear to develop to the anti-bronchoconstrictor effects of these drugs. 3. With regard to the long-acting beta 2-adrenoceptor agonists, there is evidence to suggest that tolerance develops both to their anti-bronchoconstrictor, and bronchodilator effects. Tolerance was however demonstrated in the presence of improved symptom control, therefore the clinical relevance of this phenomenon is uncertain. 4. Systemic corticosteroids can modulate lymphocyte beta 2-adrenoceptor function both preventing, and reversing tolerance. The situation regarding the effects of systemic or inhaled corticosteroids on modulating bronchodilator responses in asthmatics is less clear. There is some evidence to suggest that inhaled corticosteroids are unable to prevent bronchodilator or systemic tolerance to long-acting beta 2-adrenoceptor agonists. 5. On the basis of the current evidence, the British Thoracic Society guidelines for the management of asthma appear appropriate with regard to their recommendations for the use of long-acting beta 2-adrenoceptor agonists.