程能能药理学视角看特布他林与布地奈德雾化吸入治疗.ppt

提要 SABA的发展与治疗学价值 特布他林的药理学特点 影响ICS疗效的因素与布地奈德雾化治疗 小结 β激动剂功能性拮抗的特点 与收缩气道平滑肌的激动剂种类与剂量有关 对M激动剂的拮抗能力小于对其他激动剂 (Ca来源、R储备) 对不同哮喘患者的疗效差异与引起痉挛的介质不同有关 严重哮喘发作用时存在不同程度的抵抗 与用药时间顺序有关 翻转收缩 阻止收缩 (抑制收缩维持相起始相) 哮喘发作期疗效优于缓解期 有可逆的耐受性 受体磷酸化、内化、下调 停药1-2周可恢复 对气道平滑肌以外的作用 抑制肥大细胞脱颗粒（强于色甘酸钠2000倍) 抑制血管上皮细胞收缩，抑制血管裂隙形成，抗水肿 (ICS) 促进粘液分泌与纤毛清除功能 (雾化口服) 对嗜酸性粒细胞无明显作用 哮喘时淋巴细胞上?受体数量随疾病严重程度而降低 不降低气道高反应性 (有时反而轻度升高) 代谢：低血钾、高脂肪酸、高血糖 骨骼肌：激动慢收缩纤维?2受体，引起肌震颤 ?2受体激动剂分类 皮肤变白实验 吸入与周身糖皮质激素的相关参数比较 BUD主要经CYP3A4催化代谢，该酶主要分布于肝脏和消化道，贮留于呼吸道中的BUD几乎不被代谢。 不同吸入激素血浆皮质醇抑制程度的荟萃分析 4 * When comparing Symbicort Seretide? in COPD from separate studies., using a similar defintion of an excerbation, e.g. worsening of COPD symptoms requiring medical intervention, i.e. the addition of oral corticosteroids, antibiotics or both or hospitalisation (symbicort specific). In one large study of Symbicort, the NNT value for avoiding one exacerbation over 1 year was 2.1 versus LABA alone, this equates to preventing 48 exacerbations per 100 patients treated with Symbicort. Using the same method of analysis from the large study of Seretide?, the corresponding NNT value is approximately 14 versus LABA, this equates to preventing 7 exacerbation per 100 patients treated with Seretide? over a year. ? Given the NNT values for Symbicort in preventing an exacerbation of COPD. This would suggest treatment with Symbicort offers significant patient benefits. The rapid onset of effect after a single dose of budesonide was first documented in the 1980s (Ellul-Micallef Johansson, 1983) and was confirmed later by Engel et al (1991). In this double-blind crossover study, patients with stable asthma (n=30; mean FEV1 62% predicted normal) who normally used inhaled corticosteroids (ICS) daily, withheld steroids for 8 days before the study. Patients received a single dose of either placebo or budesonide 1600 μg and the change in FEV1 was monitored over 9 hours. The increase in FEV1 3 hours after inhalation of budesonide was significantly higher than after pl