Clinical implications of the intrinsic efficacy of beta-adrenoceptor drugs in asthma: Full, partial and inverse agonism

Purpose of review: β₂-Adrenoceptor (AR) agonists are the most effective bronchodilators known, and play important roles in every step of asthma therapy. Intrinsic efficacy is an important pharmacological property that differentiates the clinical effects and safety profile of β₂-AR agonists. We review the role of β₂-AR agonist intrinsic efficacy in asthma treatment focusing on recent literature. Recent findings: In acute asthma, a full agonist (high intrinsic efficacy) offers a clinical advantage over a partial agonist (low intrinsic efficacy) but with the potential of inducing dose-dependent adverse effects. The chronic use of β₂-AR agonists may be associated with several adverse outcomes including loss of asthma control and even increased mortality. Recently, the role of β-AR inverse agonists (beta-blockers) which have a negative intrinsic efficacy was studied. Whereas contraindicated in acute asthma, preliminary data suggest that the chronic use of these agents may be associated with attenuation of airway hyper-responsiveness in patients with mild asthma. Studies in a murine model of asthma suggest that such effects may be related to decreased airway inflammation and mucous metaplasia. Summary: Rational choice among β₂-AR agonists in acute and chronic asthma should be influenced by differences in intrinsic efficacy among these agents. In acute severe asthma, a full agonist offers a clinical advantage over a partial agonist. Whereas the use of inverse agonists in the treatment of asthma is still experimental and needs further exploration in future trials, preliminary studies suggest that their chronic use is well tolerated and is associated with decreased airway hyper-responsiveness.