Department of Internal Medicine and Geriatrics, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Curr Med Chem. 2013;20(12):1464-76. doi: 10.2174/0929867311320120002.
Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies. Their therapeutic efficacy is based on the fact that vagally mediated bronchoconstriction is the major reversible component of airflow obstruction in patients with COPD. However, bronchodilators are effective only on the reversible component of airflow obstruction, which by definition is limited, as COPD is characterized by a fixed or poorly reversible airflow obstruction. Inhaled anticholinergic antimuscarinic drugs approved for the treatment of COPD include ipratropium bromide, oxitropium bromide and tiotropium bromide. Ipratropium bromide, the prototype of anticholinergic bronchodilators, is a short-acting agent. Oxitropium bromide is administered twice a day. Tiotropium bromide, the only long-acting antimuscarinic agent (LAMA) currently approved, is administered once a day. Newer LAMAs including aclidinium bromide and glycopyrrolate bromide are currently in phase III development for treatment of COPD. Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.
支气管扩张剂，一般通过计量吸入器或干粉吸入器给药，是稳定期 COPD 药物治疗的主要手段。长效β-激动剂（LABA）和抗胆碱能药物是 COPD 慢性治疗中主要使用的支气管扩张剂。抗胆碱能药物作为毒蕈碱乙酰胆碱受体拮抗剂，由于其对心脏的刺激作用最小，且在大多数研究中效果更佳，因此常被优先选择用于β-激动剂。它们的治疗效果基于以下事实，即迷走神经介导的支气管收缩是 COPD 患者气流受限的主要可逆部分。然而，支气管扩张剂仅对气流受限的可逆部分有效，而根据定义，这是有限的，因为 COPD 的特点是存在固定或难以逆转的气流受限。批准用于治疗 COPD 的吸入性抗胆碱能药物包括异丙托溴铵、氧托溴铵和噻托溴铵。异丙托溴铵，抗胆碱能支气管扩张剂的原型，是一种短效药物。氧托溴铵每天给药两次。噻托溴铵，唯一一种目前批准的长效抗毒蕈碱药物（LAMA），每天给药一次。包括阿地溴铵和格隆溴铵在内的新型 LAMA 目前处于治疗 COPD 的 III 期开发阶段。一些新型 LAMA，包括格隆溴铵，适合每天给药一次，与噻托溴铵不同，它具有快速的起效时间。新型 LAMA 及其与超长效β-激动剂的联合应用，以及可能与吸入性皮质激素的联合应用，似乎为 COPD 的管理开辟了新的前景。双药理学毒蕈碱拮抗剂-β2 激动剂（MABA）分子通过在单个分子中结合毒蕈碱拮抗作用和β2 激动作用，为 COPD 的治疗提供了一种新方法。
