Risk versus Benefit Considerations for the β 2 ‐Agonists

Short‐acting β 2 ‐agonists are the mainstay of therapy for acute bronchospasm associated with asthma and chronic obstructive pulmonary disease, whereas long‐acting β 2 ‐agonists are used in maintaining disease control in these respiratory disorders. This review describes and compares the pharmacology of the β 2 ‐agonists and explains how these differences translate into differences in efficacy and β 2 ‐adrenergic‐mediated adverse effects. Questions commonly asked by clinicians regarding the efficacy and safety of short‐ and long‐acting β 2 ‐agonists include issues about cardiovascular effects, tolerance to their bronchodilator and bronchoprotective effects, blunting of albuterol response by long‐acting β 2 ‐agonists, potential masking of worsening asthma control, and the role of long‐acting β 2 ‐agonists as adjunctive therapy with inhaled corticosteroids in maintaining asthma control. Pharmacogenetics may play a role in determining which patients may be at risk for a reduced response to a β 2 ‐agonist. The continued use of racemic albuterol, which contains a mixture of R‐albuterol and S‐albuterol, has been questioned because of data from preclinical and clinical studies suggesting that S‐albuterol causes proinflammatory effects and may increase bronchial hyperreactivity. The preclinical and clinical effects of these two stereoisomers are reviewed. Data describing the efficacy and safety of levalbuterol (R‐albuterol) and racemic albuterol are presented.