Department of System Medicine, University of Rome Tor Vergata, Via Montpellier 1, Rome, Italy.
Am J Respir Crit Care Med. 2013 Apr 1;187(7):690-6. doi: 10.1164/rccm.201209-1739PP.
β2-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 β2-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 β2-agonists. Traditional inhaled short-acting β2-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 β2-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 β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-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 PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-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 bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent.
β2-激动剂主要通过松弛气道平滑肌（ASM）来发挥其支气管扩张作用，这是由于其与 ASM 上β2-肾上腺素能受体的活性部位结合所致。这种结合触发了一系列信号级联反应，导致许多事件的发生，所有这些都有助于 ASM 的松弛。β2-激动剂之间存在一些差异。传统的吸入型短效β2-激动剂如沙丁胺醇、特布他林和福莫特罗可迅速按需缓解症状，并在短期内预防运动或其他刺激引起的支气管收缩。每日 2 次的β2-激动剂如福莫特罗和沙美特罗是重要的进展。它们具有有效的支气管扩张作用和长期改善肺功能的特性，为患者带来了显著的临床获益。最近，发现了一种具有更长药效半衰期的新型β2-激动剂（茚达特罗），以期实现每日 1 次给药。总的来说，β2-激动剂具有可接受的安全性特征，但长期使用β2-激动剂是否会增加哮喘死亡率仍存在争议。无论如何，它们会引起不良反应，如心率加快、心悸、短暂的 PaO2 降低和震颤。β2-肾上腺素能受体在β2-激动剂治疗开始的最初几天内发生的脱敏作用可能是这些不良反应在最初几次剂量后通常会得到缓解的原因。然而，它也会导致对β2-激动剂的支气管保护作用产生耐受，并有可能降低对其的支气管扩张敏感性。一些新型的每日 1 次的β2-激动剂（奥达特罗、维兰特罗、阿布昔替醇）正在开发中，主要与吸入型皮质类固醇或长效抗毒蕈碱药物联合使用。
