华法林治疗指南讲义.ppt

华法林治疗指南;一、药理学;作用机制 ;作用机制;华法林的药化结构;令人惊奇的华法林对映体间的相互作用;药代动力学;影响药效的因素——遗传因素;Identification of the gene for vitamin K epoxide reductase Tao Li1, Chun-Yun Chang1, Da-Yun Jin1, Pen-Jen Lin1, Anastasia Khvorova2 Darrel W. Stafford1 1Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA 2Dharmacon, Inc., 1376 Miners Drive 101, Lafayette, Colorado 80026, USA Vitamin K epoxide reductase (VKOR) is the target of warfarin,the most widely prescribed anticoagulant for thromboembolic disorders. Although estimated to prevent twenty strokes perinduced bleeding episode1, warfarin is under-used because of the difficulty of controlling dosage and the fear of inducing bleeding. Although identified in 1974 (ref. 2), the enzyme has yet to be purified or its gene identified. A positional cloning approach has become possible after the mapping of warfarin resistance to rat chromosome 1 (ref. 3) and of vitamin K dependent protein deficiencies to the syntenic region of human chromosome 16 (ref. 4). Localization of VKOR to 190 genes within human chromosome 16p12-q21 narrowed the search to 13genes encoding candidate transmembrane proteins, and we used short interfering RNA (siRNA) pools against individual genes totest their ability to inhibit VKOR activity in human cells. Here,we report the identification of the gene for VKOR based on specific inhibition of VKOR activity by a single siRNA pool. We confirmed that MGC11276 messenger RNA encodes VKOR through its expression in insect cells and sensitivity to warfarin.The expressed enzyme is 163 amino acids long, with at least one transmembrane domain. Identification of the VKOR gene extends our understanding of blood clotting, and should facilitate development of new anticoagulant drugs.;影响药效的因素——药物的相互影响（一）;影响药效的因素——药物的相互影响（一）;影响药效的因素　　　——饮食;影响药效的因素　　——疾病状态;抗血栓作用;抗血栓作用的监测;二、口服抗凝治疗策略 ;抗凝强度监测 ; INR监测存在的一些问题 ;剂量与监测 （一）;剂量与监测 （二）;对于住院患者，第1和第2次服用后没有必要查INR，第3次服药后开始每日测定INR，如果连续2日INR在治