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  • Title: Effect of increasing dosage of an inhaled beta-2 specific agonist on pulmonary function, tremor, and cardiovascular indices.
    Author: Tinkelman DG, Lutz C.
    Journal: Ann Allergy; 1992 Jan; 68(1):23-6. PubMed ID: 1346562.
    Abstract:
    In this investigation we evaluated the effect of increasing dosage, using an inhaled beta-2 specific agonist, pirbuterol, administered by a metered dose inhaler on pulmonary function, tremor, and cardiovascular parameters in nonacute adult asthmatic patients. This study was conducted with a randomized crossover study design in which each individual was administered a single dose of pirbuterol (0.4, 0.8 and 1.2 mg) [corrected] on separate days. Measurements of pulmonary function, tremor (by accelerometer readings), electrocardiogram, blood pressure and pulse were obtained at 0, 15, 30, 60, 90, 120, and 180 minutes following test drug administration where appropriate. These measurements were performed until there had been no change from baseline in tremor by 60 minutes or return of tremor measurements to within 15% of baseline for up to six hours. The data demonstrated that the onset of bronchodilator effectiveness had occurred by 15 minutes after test drug administration (the first testing time). The peak percent change from baseline for the FEV1 occurred at 60 minutes after administration for all three test doses. The duration of activity was never truly established as there was no significant difference between any of the potential side effects for any of the three test drugs at any testing time period. This study demonstrated that with the beta-2 specific agent pirbuterol, administered as a metered dose inhaler, there is little risk of development of skeletal muscle or cardiovascular toxicity when as much as three times the recommended dose is used in a single usage, and that there is no direct correlation between the onset, peak, and/or duration of tremor with the onset and peak of bronchodilator efficacy with this agent.
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