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Airway subsensitivity with long-acting beta 2-agonists. Is there cause for concern?
1Department of Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee, Scotland.
Drug Safety
|May 1, 1997
Summary
Regular use of long-acting beta 2-agonists can lead to tolerance in their protective effects against asthma triggers. This airway subsensitivity may require higher doses of short-acting beta 2-agonists during acute attacks.
Area of Science:
- Pharmacology
- Respiratory Medicine
- Asthma Management
Background:
- Regular use of beta 2-agonists can cause tolerance to their protective effects, impacting long-term asthma control.
- The clinical relevance of this tolerance, particularly with long-acting beta 2-agonists (LABAs), requires further investigation.
- Genetic variations in beta 2-adrenoceptors influence individual responses to these medications.
Purpose of the Study:
- To investigate the development of tolerance and subsensitivity to the bronchoprotective and bronchodilator effects of beta 2-agonists.
- To compare the propensity for inducing receptor downregulation and subsensitivity between salmeterol and formoterol.
- To assess the impact of concomitant inhaled corticosteroid (ICS) therapy on beta 2-agonist-induced subsensitivity.
Main Methods:
- Review of existing literature on beta 2-agonist tolerance and subsensitivity.
- Analysis of receptor downregulation and functional antagonism studies.
- Comparison of effects with direct (histamine, methacholine) and indirect (exercise, allergen) stimuli.
Main Results:
- Both long- and short-acting beta 2-agonists induce tolerance to bronchoprotective effects, with no significant difference between salmeterol and formoterol in receptor downregulation.
- Subsensitivity is more pronounced with indirect stimuli than direct stimuli and is only partially reversed by ICS therapy.
- Longer-acting beta 2-agonists show a greater tendency for bronchodilator subsensitivity development compared to shorter-acting ones.
Conclusions:
- Regular use of LABAs may not be advisable for protection against indirect triggers like exercise or allergens due to induced subsensitivity.
- Patients on LABAs may require higher doses of short-acting beta 2-agonists (SABAs) for acute bronchoconstriction relief.
- Formoterol may be preferred over salmeterol for as-needed use due to its faster onset of action, when used with optimized ICS.