β2-Agonist Therapy in Lung Disease

beta(2)-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of beta(2)-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between beta(2)-agonists. Traditional inhaled short-acting beta(2)-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily beta(2)-Agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer beta(2)-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, beta(2)-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting beta(2)-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in Pa-O2, and tremor. Desensitization of beta(2)-adrenoceptors that occurs during the first few days of regular use of beta(2)-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to broncho-protective effects of beta(2)-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily beta(2)-Agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent.