Oct 22, 1992

Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma

The New England Journal of Medicine
B J O'ConnorP J Barnes

Abstract

Tolerance to the direct bronchodilator effects of beta 2-agonists does not appear to occur in asthma. However, it is not known whether this is true for the nonbronchodilator effects of these agents, which protect the airways against bronchoconstrictive stimuli. We investigated whether tolerance develops to the protective effect of inhaled terbutaline on airway responsiveness to the bronchoconstrictors methacholine (which acts directly on airway smooth muscle) and AMP (which acts indirectly by stimulating the release of mediators from mast cells) during sustained treatment with terbutaline. In a randomized, double-blind, crossover study, 12 patients with mild asthma each inhaled a single dose of terbutaline (500 micrograms) or placebo before a challenge with a series of doubling doses of inhaled methacholine or AMP, before and after treatment for seven days with 500 micrograms of terbutaline four times daily or placebo. Before the seven days of treatment with terbutaline, a single dose of terbutaline reduced airway responsiveness to methacholine by 2.7 doubling doses (95 percent confidence interval, 1.9 to 3.5), but it had an even greater protective effect against AMP, reducing airway responsiveness by 3.8 doubling doses (95 per...Continue Reading

Mentioned in this Paper

Bronchial System
Inhalation of Drugs
Mast Cell
Drug Tolerance
Bronchoconstrictor Agents
Smooth Muscle
Adrenergic beta-Agonists
Bronchodilator Effect
Terbutalin von ct
Bronchodilator Agents

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