Tolerance with beta 2-adrenoceptor agonists: time for reappraisal

Area of Science:

• Pharmacology
• Respiratory Medicine
• Clinical Therapeutics

Background:

• Beta 2-adrenoceptor agonists are widely used for asthma, but their role in asthma morbidity and mortality is controversial.
• The development of tolerance to bronchodilator and anti-bronchoconstrictor effects is a key area of investigation.

Purpose of the Study:

• To review the evidence regarding tolerance to beta 2-adrenoceptor agonists in asthma.
• To assess the clinical relevance of tolerance and the role of corticosteroids in modulating these effects.

Main Methods:

• Literature review of studies investigating tolerance to short-acting and long-acting beta 2-adrenoceptor agonists.
• Examination of the impact of systemic and inhaled corticosteroids on beta 2-adrenoceptor function and drug responses in asthma.

Main Results:

• Tolerance to the anti-bronchoconstrictor effects of short-acting beta 2-adrenoceptor agonists is evident, but not to bronchodilator effects.
• Tolerance to both bronchodilator and anti-bronchoconstrictor effects of long-acting beta 2-adrenoceptor agonists is suggested, though clinical relevance is uncertain.
• Corticosteroids can modulate beta 2-adrenoceptor function, but inhaled corticosteroids may not prevent tolerance to long-acting beta 2-adrenoceptor agonists.

Conclusions:

• Current evidence does not conclusively link tolerance to beta 2-adrenoceptor agonists with increased asthma mortality.
• The clinical significance of tolerance, particularly for long-acting agents, requires further investigation.
• Existing asthma management guidelines appear appropriate regarding the use of long-acting beta 2-adrenoceptor agonists.