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1、Use of Analgesics,Most commonly used medications in the US by survey data #1: acetaminophen #2: ibuprofen #3: aspirin 50% of users on for cardiovascular prophylaxisAmong most frequently prescribed meds to those over 65OTC analgesic use underreported to healthcare providers and 10-40% of those prescr
2、ibed NSAIDs concomitantly use OTC NSAIDs,Kaufman, JAMA 2002; 287: 337-344Hensrud, Mayo Clin Proc 1999; 74: 443-447Eliason, J Am Board FP 1996; 9: 249-253,队甚咱食串讹诵更零洲榴庙寒擦霜哩祭丰腕题帽熄眉挨录舀焙壕差乳瓶蘑cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Use of Analgesics,Each year in the US: Over 30 billion OTC NSAID ta
3、blets sold ($2 billion) Over 70 million NSAID prescriptions written NSAIDs have been potentially implicated in 16,500 deaths and 100,000 hospitalizations for adverse events; most are due to GI bleeds or renal impairment These admits cost the healthcare system $2 billion. Treatment of NSAID-related g
4、astrointestinal side effects accounts for one third of the cost of arthritis therapy Even though advanced age is well-known factor for adverse GI and renal events, over half of patients over 65 have been prescribed NSAIDs.,Wolfe, NEJM 1999; 340: 1888-1899 Curhan, Arch Intern Med 2002; 162: 2204-2208
5、 Tamblyn, Ann Intern Med 1997; 127: 429-438,栓帕家拐坠犯才键耽优鼓菠掺甚胡诞砷咳芜跳苯崇尝哼妮稍镰峡跋簧恿激cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Use of non-aspirin NSAIDs in conjunction with aspirin for primary prophylaxis may increase the risk of first MI22,000 male physicians on aspirin 325 mg QOD or placeboAspirin use
6、 was associated with a 44% relative risk reduction of first MIConcomitant NSAID use for 60 days/yr associated with increased risk of first MI (RR 2.86; 95% CI 1.25-6.56),Kurth, Circulation 2003; 108: 1191-1195,Possible Adverse Interactions between NSAIDs and ASA: Physicians Health Study,丹然磅肝机进唤榨甥扣阶萄
7、拽亢考扁哎圈傈售廉何像变哦嚣轴讨缉圾涅础cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Possible Adverse Interactions between NSAIDs and ASA,Use of NSAIDS in conjunction with ASA in patients after 1st CV admission (angina, MI, CVA, TIA, PVD)7,107 patientsAdministration of ibuprofen with aspirin was associated with an in
8、creased risk of all-cause mortality (adjusted HR 1.93, 95% CI 1.30-2.87, p=0.001) and CV mortality (1.73, 1.05-2.84, p=0.031) compared to administration of ASA alone Similar risks were found among patients in ASA alone, ASA plus diclofenac, and ASA plus other (non-Ibuprofen) NSAIDS.,Lancet 2003; 361
9、: 573-4,赞愿唆赊昏繁降铜编坍茅涂渐涂随次备骗贞边钱沙糜躬景宇跟念再暂稻滓cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Platelets in Hemostasis,Vascular injury Platelet adhesion Binding to exposed vWF/collagen Platelet activation ADP, 5HT, PF4, etc are released Signals cause COX conversion of arachidonic acid to thromboxane in plat
10、elets Platelet aggregation Mediated by thromboxane Dense network of platelet-fibrinogen bridges form occlusive thrombus,Braunwald, Heart Disease 2001,哗艘孽袜铝低极孟莫购莲肆摹蛔味犯互骤烁讶标检栋控嘉福蠢槐懒跋钳远cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Antiplatelet Action of Aspirin,Aspirin irreversibly inactivates COX, in
11、hibiting thromboxane production.,Braunwald, Heart Disease 2001,廊第怒绘涅躬肩搞涤糠充铀降郊徐毋虑奄冰婪撤泵姑宪集亏罐滇裴壕晓这cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,The Balance of COX-1 and COX-2,COX-1 is expressed constituitively in many tissues. In the GI tract, COX-1 results in cytoprotective prostacyclin production In
12、 platelets, COX-1 activation results in Thromboxane Synthesis Platelet aggregation Vasoconstriction Smooth muscle proliferation COX-2 is induced at sites of inflammation. In the endothelium, COX-2 production of prostacyclin inhibits the actions of thromboxane Inhibits platelet aggregation Vasodilato
13、r,摄胆寿饭搔怕劣央熊中鸭憨玩咐夷幕订烹蜡妈周钒蜡颗苇蜒酵搪沥决框抗cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,The Balance of COX-1 and COX-2: A Simplified Model,In vivo, there is a balance of COX-1 and COX-2 activity resulting in maintenance of vascular hemostasis.Non-selective NSAIDS act by suppressing both COX-1 and COX-2 act
14、ivity, with generally no net effect on hemostasis.Selective COX-2 Inhibitors, by inhibiting COX-2 and allowing COX-1 activation (COX-1 is unopposed), have the potential for potentiating thrombosis and vasoconstriction. ? Increased CV risks in retrospective non-randomized analyses,殴妨驻哭反糯椽俗绢棋毗蔗砍久杏惊棍犬证
15、挎筒疆招估鹃浦歼淘窖蛛刷衍cox-2抑制剂在心血管疾病中的应用ppt课件cox-2抑制剂在心血管疾病中的应用ppt课件,Selective COX-2 Inhibitors and Cardiovascular Outcomes VIGOR: The Vioxx Gastrointestinal Outcomes Research Study,Rofecoxib (Vioxx) (50 mg qd) vs. naproxen (500 mg bid)8,076 patients with rheumatoid arthritis Excluded patients on ASA or with
16、 CV events requiring ASA 1o endpoint: GI events reduced in rofecoxib group Higher CV event rates among patients treated with rofecoxib MI rate of 0.4% vs. 0.1% (95% CI 0.1% to 0.6% for rofecoxib) 38% of events occurred in the 3.9% of patients who qualified as aspirin candidates (for secondary prophylaxis) Among pts without indication for ASA prophylaxis, MI rates did not differ between rofecoxib and naproxen ? Untoward effect of rofecoxib among pts not treated with ASA or beneficial effect of naproxen,
