Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
Drug Saf. 1992 Jan-Feb;7(1):54-70. doi: 10.2165/00002018-199207010-00007.
The therapeutic goal for the treatment of asthma should be to suppress bronchial mucosal inflammation with preventive drugs such as inhaled corticosteroids, and to relieve symptoms of wheezing and breathlessness with bronchodilator drugs. The lower recommended doses of inhaled beta 2-agonists produce rapid effective bronchodilatation without systemic adverse effects; higher doses may produce substantial improvements in airway response which may help patients with more severe airflow obstruction. Higher doses of inhaled beta 2-agonists also cause dose-related systemic adverse beta 2 effects including tremor, tachycardia, hypokalaemia and associated electrocardiographic sequelae. In this respect, although fenoterol appears to cause greater extrapulmonary beta 2-mediated adverse effects at higher doses, there is no evidence to suggest that it is any less beta 2-selective. There is also some evidence to suggest that use of regular inhaled beta 2-agonists may cause increased bronchial hyperreactivity and possibly deterioration in disease control. Patients who require such regular use should therefore be given additional anti-inflammatory therapy with inhaled corticosteroids. The recent availability of novel, longer-acting inhaled beta 2-agonists such as salmeterol and formoterol will also make necessary a careful reappraisal of their long term use in patients with asthma.
哮喘治疗的目标应是使用吸入性糖皮质激素等预防性药物抑制支气管黏膜炎症，并使用支气管扩张剂缓解喘息和呼吸急促症状。吸入性β2激动剂的推荐较低剂量可产生快速有效的支气管扩张，且无全身不良反应；较高剂量可能会使气道反应有显著改善，这可能有助于更严重气流受限的患者。较高剂量的吸入性β2激动剂还会引起与剂量相关的全身β2不良反应，包括震颤、心动过速、低钾血症及相关的心电图后遗症。在这方面，尽管非诺特罗在较高剂量时似乎会引起更大的肺外β2介导的不良反应，但没有证据表明它的β2选择性更低。也有一些证据表明，长期使用吸入性β2激动剂可能会导致支气管高反应性增加，并可能使疾病控制恶化。因此，需要经常使用此类药物的患者应接受吸入性糖皮质激素的额外抗炎治疗。最近新型长效吸入性β2激动剂如沙美特罗和福莫特罗的出现，也有必要对它们在哮喘患者中的长期使用进行仔细的重新评估。
