In vivo effect of albuterol on methacholine-contracted bronchi in conjunction with salmeterol and formoterol
Summary
This summary is machine-generated.Long-acting beta2-agonists like salmeterol and formoterol antagonize the bronchodilator effect of albuterol in asthma patients. This interaction, potentially due to receptor occupancy or tachyphylaxis, is influenced by beta2-adrenoceptor gene variations.
Area Of Science
- Pharmacology
- Respiratory Medicine
- Clinical Trials
Background
- In vitro studies indicate that long-acting beta2-agonists (LABAs) like salmeterol and formoterol can antagonize the bronchodilator effects of short-acting beta2-agonists (SABAs) such as albuterol.
- This antagonism has been observed in carbachol-contracted human bronchi.
Purpose Of The Study
- To investigate in vivo interactions between LABAs (formoterol, salmeterol) and SABAs (albuterol) in asthmatic patients with increased airway tone.
- To explore the influence of beta2-adrenoceptor polymorphisms on these interactions.
Main Methods
- A double-blind, placebo-controlled, cross-over study involving 16 asthmatic subjects.
- Subjects received inhaled corticosteroids and were randomized to placebo, formoterol, or salmeterol, followed 12 hours later by low or high doses of albuterol.
- Airway responsiveness was assessed via methacholine challenges performed one hour after albuterol administration.
Main Results
- Salmeterol and formoterol significantly antagonized albuterol-induced bronchorelaxation compared to placebo.
- While high-dose albuterol combined with LABAs showed numerically lower PD20 values, the difference was not statistically significant.
- A significant difference was observed in low-dose albuterol PD20 values when combined with formoterol or salmeterol compared to high-dose albuterol with placebo.
- Post hoc analysis revealed that beta2-adrenoceptor polymorphisms (Gly16 and Glu27) were associated with significantly lower PD20 values.
Conclusions
- Both salmeterol and formoterol antagonize albuterol-induced bronchodilation in vivo in methacholine-challenged asthmatic airways.
- This antagonism may result from prolonged beta2-adrenoceptor occupancy or early tachyphylaxis following LABA exposure.
- The effectiveness of albuterol in providing bronchodilation is influenced by individual beta2-adrenoceptor genetic variations.
View abstract on PubMed