Clinical implications of the intrinsic efficacy of beta-adrenoceptor drugs in asthma: full, partial and inverse agonism.
Clinical implications of the intrinsic efficacy of beta-adrenoceptor drugs in asthma: full, partial and inverse agonism.
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DOI：
10.1097/mcp.0b013e328333def8
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发表时间：
2010-01
影响因子：
3.3
通讯作者：
Bond RA
中科院分区：
文献类型：
--
作者：
Hanania NA;Dickey BF;Bond RA
肾上腺素能受体(β2-adrenoceptor，AR)激动剂是目前已知的最有效的支气管扩张剂，在哮喘治疗的每一步都发挥着重要作用。内在疗效是区别2AR激动剂临床疗效和安全性的重要药理学特性。我们回顾了2-肾上腺素能受体激动剂在哮喘治疗中的内在疗效的作用，重点是最近的文献。在急性哮喘中，完全激动剂(高内在有效性)比部分激动剂(低内在有效性)具有临床优势，但有可能导致剂量依赖的不良反应。2-AR激动剂的长期使用可能与几种不良后果有关，包括哮喘失去控制，甚至增加死亡率。最近，对β受体反向激动剂(β-受体阻滞剂)的作用进行了研究，这些药物具有负的内在效应。虽然急性哮喘是禁忌，但初步数据表明，这些药物的长期使用可能与轻度哮喘患者的呼吸道高反应性减弱有关。对哮喘小鼠模型的研究表明，这种作用可能与减少呼吸道炎症和粘液化生有关。急、慢性哮喘患者β-2AR激动剂的合理选择应受其内在疗效差异的影响。在急性重症哮喘中，完全激动剂比部分激动剂具有临床优势。虽然反向激动剂在哮喘治疗中的使用仍处于实验阶段，还需要在未来的试验中进一步探索，但初步研究表明，长期使用这些药物是安全的，并与降低呼吸道高反应性有关。
β2-adrenoceptor (AR) agonists are the most effective bronchodilators known, and play important roles in every step of asthma therapy. The intrinsic efficacy is an important pharmacological property that differentiates the clinical effects and safety profile of ß2AR agonists. We review the role of ß2-AR agonist intrinsic efficacy in asthma treatment focusing on recent literature. In acute asthma, a full agonist (high intrinsic efficacy) offers a clinical advantage over a partial agonist (low intrinsic efficacy) but with the potential of inducing dose-dependent adverse effects. The chronic use of ß2-AR agonists may be associated with several adverse outcomes including loss of asthma control and even increased mortality. Recently, the role of βAR inverse agonists (beta-blockers) which have a negative intrinsic efficacy was studied. While contraindicated in acute asthma, preliminary data suggest that the chronic use of these agents may be associated with attenuation of airway hyperresponsiveness in patients with mild asthma. Studies in a murine model of asthma suggest that such effects may be related to decreased airway inflammation and mucous metaplasia. Rational choice among β2AR agonists in acute and chronic asthma should be influenced by differences in intrinsic efficacy among these agents. In acute severe asthma, a full agonist offers a clinical advantage over a partial agonist. While the use of inverse agonists in the treatment of asthma is still experimental and needs further exploration in future trials, preliminary studies suggest that their chronic use is safe and is associated with decreased airway hyperresponsiveness.