Clinical implications of the intrinsic efficacy of beta-adrenoceptor drugs in asthma: full, partial and inverse agonism.
OBJECTIVE
beta2-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 beta2-AR agonists. We review the role of beta2-AR agonist intrinsic efficacy in asthma treatment focusing on recent literature.


RESULTS
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 beta2-AR agonists may be associated with several adverse outcomes including loss of asthma control and even increased mortality. Recently, the role of beta-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.


CONCLUSIONS
Rational choice among beta2-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.
Hanania
Nicola A
NA
Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Hanania@bcm.edu
Dickey
Burton F
BF
Bond
Richard A
RA
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents