信必可药理学剖析课件.ppt

剂型吸入装置: 都保 气道靶向性给药装置 吸入器对吸入治疗效果的影响 肺沉积率 (Thorsson et al, 1998) 都保是加压定量吸入器的2倍 减少药量 依从性 (Cochrane et al, 2000, Bosley et al, 1994) 都保吸入器平均依从率86% 平均依从率20~73% 吸入不足24~69%;吸入过量2~23% 方便性 (Cochrane et al, 2000) 易携带 体积小 60吸在手 吸次少 旋转顺滑 对都保偏好的OR比值 2.94 (95%CI=1.74 - 4.89, P0.001) 0 5 10 15 20 25 0 5 10 15 20 25 30 35 微细颗粒(直径 5 μm)剂量率(标示量) 肺沉积率% (标示量) mean ± SEM R=0.94 Turbuhaler pMDI Cyclohaler Rotahaler 沙丁胺醇, 体内 –体外相关性 Olsson et al., 1996 0 % 0 10 20 30 (L) 2.5 3.0 pMDI Turbuhaler 40 Borgstr?m et al., 1996 微细颗粒剂量 肺沉积率 FEV1 In-vitro, in-vivo clinical effect 0.25 mg terbutaline 总结 布地奈德和福莫特罗协同作用于哮喘和COPD的发病环节； 在细胞、受体和分子水平相互作用导致抗炎作用增强、保持激素受体和?2受体功能； 布地奈德和福莫特罗均表现为： 起效迅速 疗效随剂量增加； 作用持久； 大剂量时耐受良好； 都保吸入器提高药物气道选择性，治疗方便、可靠. The term synergy is traditionally used to describe the quality of the effect produced when two different agents are given together and includes both an additive effect (1+1=2) and a potentiation (1+12). * The efficacy of single inhaler therapy is dependant on 3 important factors: The pharmacological properties of the individual mono-components The molecular interactions between the mono-components The formulation and inhalation device used to deliver the medication * * * Several processes are involved, the deposition of the GCS at the airway mucosa, its rate of dissolution, the counteracting mucociliary clearance, the actual cellular uptake and metabolism, the specific receptor binding and subsequent translocation to the nucleus or binding with transcription factors, the unspecific intracellular binding and retentionand eventually the release and diffusion into the systemic circulation. golgi-apparatus: One function is as storage of cellmembrane material and cohlesterol for steroid hormone synthesis. lysosomes: containing digestive enzymes (eg proetolytic, phosphatases, ) fuses with material which is engulfed by pinocytosis or phagocytosis for digestion. Engulfs particles, dust and undissolved aerosols in lung. Cortisol interacts with the