Regular use of inhaled β-agonist leads to tolerance to its bronchoprotective effect. This occurs within 12 hours with salmeterol and has been documented at 1 week for salbutamol (the medication name albuterol is used in the U.S). This study aimed to determine the course of onset of tolerance to the bronchoprotective effect of salbutamol against methacholine. It was designed as a randomized, double-blind, placebo-controlled trial and included 13 patients with mild asthma. Each treatment period consisted of 7 twice-daily doses (2 puffs of 100 μg of salbutamol or placebo). Methacholine challenges were conducted 24 hours apart on 4 consecutive days, 10 minutes after the first, third, fifth, and seventh doses.
A single dose of salbutamol shifted the methacholine PC20 approximately 5-fold from a geometric mean of 2.1 mg/mL to 10.7 mg/mL. Maximal bronchoprotection after the active treatment occurred on day 2 after the third dose. After the fifth dose the methacholine PC20 was trending downward, and on day 4 the bronchoprotective effect of salbutamol had significantly decreased from its peak protection.
The authors concluded that the detrimental effects on bronchoprotection after regular use of salbutamol manifest after 5 doses and are significantly reduced from peak protection after 7 doses.
Asthma Inhalers (click to enlarge the image).
References:
Salbutamol tolerance to bronchoprotection: course of onset. Sarah L. Stewart, BSc, Alexandra L. Martin, BSc, Beth E. Davis, BSc, PhD, Donald W. Cockcroft, BSc, MD, FRCP(C). Annals of Allergy, Asthma & Immunology, Volume 109, Issue 6 , Pages 454-457, December 2012.
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