Section of Pulmonary, Critical Care, Allergy, and Immunologic Diseases, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Semin Respir Crit Care Med. 2010 Jun;31(3):321-33. doi: 10.1055/s-0030-1254072. Epub 2010 May 21.
Beta-2 adrenergic agonists are sympathomimetic agents that stimulate bronchodilation by activation of adenyl cyclase to produce cyclic 3'5' adenosine monophosphate (AMP). Short-acting beta-agonists (SABAs) have a 3- to 6-hour duration of action, and the duration of action of long-acting beta-agonists (LABAs) exceeds 12 hours. Because of their rapid onset of action, SABAs are effective for rescue from symptoms of chronic obstructive pulmonary disease (COPD). LABAs-salmeterol and formoterol-have been shown to significantly improve lung function, health status, and symptom reduction, compared with ipratropium. Despite safety concerns over the use of LABAs as monotherapy in asthma the use of these medications in COPD has generally been described as safe. Novel bronchodilators for COPD in late-stage development include the beta-agonists indacterol and carmoterol. Parasympathetic activity in the large and medium-size airways is mediated through the muscarinic receptors and results in airway smooth-muscle contraction, mucus secretion, and possibly increased ciliary activity. Although short-acting ipratropium has been used as monotherapy or in combination with albuterol the use of long-acting antimuscarinics is superior in improving health outcomes. The use of tiotropium results in improved health status, dyspnea, and exercise capacity, and reduced hyperinflation and COPD exacerbation rate in patients with moderate to severe COPD. Analysis of prospective clinical trial data shows a mortality reduction in subjects treated with tiotropium, despite retrospective review of insurance claims that show an enhanced mortality. Theophylline is a nonselective phosphodiesterase inhibitor that acts as both a weak bronchodilator and a respiratory stimulant. Novel approaches include using the inhalation route to reduce side effects and combination with inhaled corticosteroids (ICS). However, because of its potential adverse effects and narrow therapeutic index, it should only be used when symptoms persist despite optimal bronchodilator therapy. Current guidelines highlight that for COPD patients uncontrolled by bronchodilator monotherapy, combination therapy is recommended. These include LABA/ICS and LAMA/LABA combinations. Bronchodilators and their combination with ICS are central to the management of COPD. The choice of agents is based primarily on disease stage, individual response, cost, side effect profile, and availability.
β-2 肾上腺素能激动剂是拟交感神经药物，通过激活腺苷酸环化酶刺激支气管扩张，产生环 3'5' 一磷酸腺苷 (AMP)。短效 β-激动剂（SABA）的作用持续时间为 3 至 6 小时，长效 β-激动剂（LABA）的作用持续时间超过 12 小时。由于其起效迅速，SABA 可有效缓解慢性阻塞性肺疾病（COPD）的症状。LABA-沙美特罗和福莫特罗与异丙托溴铵相比，显著改善了肺功能、健康状况和症状缓解。尽管在哮喘中使用 LABA 作为单一疗法存在安全性问题，但这些药物在 COPD 中的使用通常被描述为安全的。处于后期开发阶段的 COPD 新型支气管扩张剂包括β激动剂茚达特罗和卡莫特罗。大气道和中气道的副交感神经活动通过毒蕈碱受体介导，导致气道平滑肌收缩、黏液分泌，并可能增加纤毛活动。尽管短效异丙托溴铵已被用作单一疗法或与沙丁胺醇联合使用，但长效抗毒蕈碱药物在改善健康结果方面更为优越。噻托溴铵的使用可改善健康状况、呼吸困难和运动能力，并降低中重度 COPD 患者的过度充气和 COPD 恶化率。对前瞻性临床试验数据的分析表明，接受噻托溴铵治疗的患者死亡率降低，尽管对保险索赔的回顾性审查显示死亡率增加。茶碱是一种非选择性磷酸二酯酶抑制剂，既是一种弱支气管扩张剂，也是一种呼吸兴奋剂。新方法包括使用吸入途径减少副作用，并与吸入性皮质类固醇（ICS）联合使用。然而，由于其潜在的不良反应和狭窄的治疗指数，只有在最佳支气管扩张剂治疗后症状持续存在时才应使用。目前的指南强调，对于不能通过支气管扩张剂单一疗法控制的 COPD 患者，推荐联合治疗。这些包括 LABA/ICS 和 LAMA/LABA 联合治疗。支气管扩张剂及其与 ICS 的联合应用是 COPD 管理的核心。药物的选择主要基于疾病阶段、个体反应、成本、副作用谱和可用性。
