丁丙诺啡透皮贴剂.pptxVIP

丁丙诺啡透皮贴剂的药理作用CN-NOR-0551-V1-1114提纲丁丙诺啡对阿片受体系统的作用丁丙诺啡是?受体部分激动剂，同时拮抗?受体和激动?受体1效应?受体（%）?受体（%）?受体（%）阿片受体样受体ORL1（%）DAMGO100DPDPE100U50,488H100Nociceptin/OFQ100去甲基丁丙诺啡81?496?360?2130?14丁丙诺啡38?8最大1?M也无刺激作用10?460?10DAMGO，DPDPE，U50,488H和N/OFQ分别是不同阿片受体的完全激动剂。Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004;2(4):395-402.Huang P, et al. Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther. 2001;297(2):688-95.丁丙诺啡的内在活性较小丁丙诺啡是阿片受体部分激动剂，内在活性（intrinsic activity）比吗啡和芬太尼低。阿片受体激动剂和拮抗剂药的内在活性比较（GTPγS最大刺激结合试验）SH-SY5Y（人）CHO（人）CHO（小鼠）C6（大鼠）丘脑（大鼠）丁丙诺啡6666435110DAMGO100100100100100芬太尼90100979058吗啡74931068356纳诺酮0000NDSH-SY5Y人神经母细胞瘤细胞，CHO=中国仓鼠卵巢细胞，C6= C6胶质瘤细胞，DAMGO是阿片受体完全激动剂，ND=不确定Robert B. Raffa, Zhe Ding. Examination of the preclinical antinociceptive efficacy of buprenorphine and its designation as full- or partial-agonist. Acute Pain. 2007;9:145-152.丁丙诺啡的镇痛作用按镇痛作用的等效比，丁丙诺啡相比吗啡是75?100:11丁丙诺啡镇痛比吗啡和芬太尼更持久2,3丁丙诺啡预镇痛效果明显优于吗啡4多种给药途径（含透皮贴和皮下给药）5Sittl R. Transdermal buprenorphine in cancer pain and palliative care. Palliat Med. 2006;20 Suppl 1:s25-30.Edge WG, et al. Analgesic effects of sublingual buprenorphine. Anaesthesia 1979;34:463–467.Kay B. A double-blind comparison between fentanyl and buprenorphrine in analgesic-supplemented anaesthesia. Br J Anaesth. 1980;52(4):453-7.Kay B. A double-blind comparison of morphine and buprenorphine in the prevention of pain after operation. Br J Anaesth. 1978;50(6):605-9.Vadivelu N, Hines RL. Buprenorphine: a unique opioid with broad clinical applications. J Opioid Manag. 2007;3(1):49-58.丁丙诺啡的镇痛作用与刺激强度相关不同温度下丁丙诺啡的镇痛作用呈现“钟形”剂量-效应曲线。低强度痛觉刺激下，丁丙诺啡显示完全的镇痛作用。痛觉强度更高时，丁丙诺啡疗效较低。老鼠热痛觉模型中不同温度下丁丙诺啡镇痛作用的剂量-效应曲线Robert B. Raffa, Zhe Ding. Examination of the preclinical antinociceptive efficacy of buprenorphine and its designation as full- or partial-agonist. Acute Pain. 2007; 9: 145-152.丁丙诺啡独特的镇痛效应：激动?受体同时活化ORL-1受体丁丙诺啡的是部分激动剂，通过?受