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精品抗血小板药的临床选择课件_3

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精品 血小板 临床 选择 课件 _3
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Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 抗血小板药的临床选择 李家增 教授 中国医学科学院血液学研究所 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 血小板的生理功能 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 生 理 性 止 血 过 程 限制血流 血管收缩 凝血酶 纤维蛋白 XIIXII VIIVII 血小板释放 ADP TXA2 PAF IP3 血小板聚集成栓 胶原 微纤维 血小板黏附 血管期血管期 细胞期细胞期 初步止血初步止血 血浆期血浆期 加固止血加固止血 血管受损 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 血小板与血栓形成 血小板受体血小板受体 未激活的血小板未激活的血小板 接触和聚集 继发继发 黏附黏附 滚动 接触 黏附黏附 颗粒颗粒 释放释放 扩展扩展 内皮细胞内皮细胞在内皮下在内皮下 vWFvWF沉积沉积 胶原胶原 初期血小板黏附初期血小板黏附 血小板聚集 血小板聚集 增长的血栓增长的血栓 激活的激活的 血小板血小板 继发 黏附 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 动 脉 血 栓 形 成 机 制 动脉 高流速 静脉 低流速下 血小板血血 流流 动 脉 T M T M PGIPGI 2 2 血流血流 血小板 静 脉 凝固系凝固系 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 抗血小板药的类型 v 口服抗血小板药 阿斯匹林 抵克力得 波立维 西洛他唑 安步乐克 v 贝前列腺素 德纳 静脉抗血小板药 阿昔单抗 欣维宁等 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 抗血小板药作用机制 v 环氧化酶抑制剂 阿司匹林 v 磷酸二酯酶抑制剂 西洛他唑 培达 v ADP 受体抑制剂 波立维 氯吡格雷 v 5 羟色胺受体抑制剂 安步乐克 v 血小板 GP b a 拮抗剂 Abciximab Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林的抗血小板作用 胶原 5 羟色氨 ADP 凝血酶 TXA2 刺激传 递系统 肾上腺素 cAMP Ca 释放反应 GP IIb GP IIIa Ca GP IIIa GP IIb 纤维蛋白原 聚集 Aspirin Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林药代动力学 v 服药后 30 40 分钟出现血浆峰值 肠溶片 3 4 小时 v 服药后 1 小时抑制血小板聚集 v 生物利用度 40 50 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林有效的疾病及有效剂量 疾病每日最低有效剂量 mg 有高危的人75 高血压75 稳定性心绞痛75 不稳定性心绞痛75 急性心梗160 一时性缺血和缺血性卒中50 严重的颈动脉狭窄75 急性缺血性卒中160 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林的两难选择 血管内皮细胞膜 血栓素合成酶 磷脂酶 A2 磷 脂 血小板细胞膜 花生四烯酸 PGG2 PGH2 TXA2PGI2 血管收缩血管舒张 促进血小板聚集 抑制血小板聚集 磷 脂 环氧化酶 氢过氧化物 前列环素合成酶 Aspirin x Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林反应者和阿司匹林无反应者 无事件率 中风 114 例有反应者和 60 例无反应者的随访超过 24 个月 01510152024 50 100 60 70 80 90 观 察 月 数 无事件患者数 中风 心梗 血管性死亡 阿司匹林反应者 n 114 全部患者 n 174 阿司匹林无反应者 n 60 Grotemeyer K H et al Thrombosis Research 71 1993 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿司匹林抵抗 健康受试者 n 8 Aspirin 324 mg 服药后 2 小时 血小板聚集Template IIR Bleeding Time Light transmission 100 80 60 40 20 0 0 115 胶原 g ml Non Responders n 3 Responders n 5 无反应者 Bleeding time sec 1000 800 600 400 200 0 1200 有反应者 BeforeAfterBeforeAfter Kawasaki T Stroke 31 591 2000 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 氯吡格雷作用机制 胶原 5 羟色氨 ADP 凝血酶 TXA2 刺激传 递系统 肾上腺素 cAMP Ca 释放反应 GP IIb GP IIIa Ca GP IIIa GP IIb 纤维蛋白原 聚集 X Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 药 代 动 力 学 v 肠道吸收 肝脏代谢 2 2 2 4 尿中排泄 v 服药后 0 9 1 1 小时达到峰值 2 小时起效 v 半减期为 7 2 7 5 小时 v 连服 3 7 天后 达到稳定浓度 0 08 0 11mg L v 停药后作用可延续到 7 10 天 洗脱期长 氯吡格雷 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 氯吡格雷副作用 v 出血 v 引起中性粒细胞减少和血小板减少 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 西洛他唑作用机制 胶原 5 羟色氨 ADP 凝血酶 TXA2 刺激传 递系统 肾上腺素 cAMP Ca 抑制一次聚集同时抑制引起二次聚集的化学物质的释放 GP IIb GP IIIa Ca GP IIIa GP IIb 纤维蛋白原 聚集 cAMPcAMP 血小板惰性化 X X Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 药 代 动 力 学 v 肠道吸收 肝脏代谢 给药 72 h 后 42 7 尿 中排泄 v 作用快速 3 5 h 最强 3 h 达到最高血药浓 度 有效浓度 24 h 以上 72 h 后尿中排泄 连续给予西洛他唑 4 日 每日 2 次 未见 血药浓度蓄积上升 v 洗脱期短 伴随血药浓度的降低而抗血小板 作用迅速下降 v 不延长出血时间 不增加出血量 西洛他唑 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 阿昔单抗作用机制 胶原 5 羟色氨 ADP 凝血酶 TXA2 刺激传 递系统 肾上腺素 cAMP Ca 释放反应 GP IIb GP IIIa Ca GP IIIa GP IIb 纤维蛋白原 聚集 X Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 药代动力学 临床应用 不良反应 v 药代动力学 药后 10 分钟抑制血小板聚集 4 小时完全抑制 24 小时回升 48 小时恢复到基础水平的 35 v 临床应用 适用于 PCI 24 小时内作 PCI 的顽固性不稳定 性心绞痛和无 Q 波心肌梗死 v 不良反应 出血 血小板减少 产生人抗嵌合体抗体 可在 半年内消失 阿昔单抗 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 安步洛克作用机制 胶原 5 羟色氨 ADP 凝血酶 TXA2 刺激传 递系统 肾上腺素 cAMP Ca 释放反应 GP IIb GP IIIa Ca GP IIIa GP IIb 纤维蛋白原 聚集 X 萘呋胺酯 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 药代动力学 临床应用 不良反应 v 药代动力学 胃肠吸收 1 5 小时达到峰值 持续 4 6 小 时 12 小时后有回复倾向 尿中排泄 v 临床应用 用于慢性动脉闭塞症 v 不良反应 皮疹 恶心 胃灼感 安步乐克 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 多种药物的抗血小板作用 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 口服血小板 GP b a 拮抗剂 v Xemilcfiban v Orbofiban v Sibrafiban v Lotrafiban v Roxifiban Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 静脉抗血小板药 v 静脉注射血小板 GP b a 拮抗剂 Abciximab Eptifibatide Integrilin Aggratat Titofiban Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 三种抗血小板药的比较 AbciximabEprifibabideTirofiban 结构抗体片断环状6肽酪氨酸衍生物 剂量 0 25 mg kg bolus 0 125 ug kg min 输 注 180ug kg bolus 2 ug kg min 输注 0 4 ug kg min 输注 30 分 0 1 kg min 输注 排出多因素肾肾 肾功不良时的剂 量 慎用肌酸酐 dl 需减量 CrCl 30 ml min 时 减量 伴发血小板减少必须计 数血小板无或很少 无或很少 但应监测 血 小板 有关 ACS CAPTURE GUSTO IV ACS PURSUIT PRISM PRISM PLUS FDA 仅在高危患者 18 h 内 准备做 PCI 批准用于 ACS批准用于ACS Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 其 他 抗 血 小 板 药 产 品抗血小板机制血管效应 腺嘌呤环化酶激活剂 如 PGI2 类似物 cAMP扩张 血管 乌嘌呤环化酶激活剂 如 NO 供体 cAMP扩张 血管 磷酯酶II抑制剂 如 西洛他唑 cAMP扩张 血管 5 HT 拮抗剂 如 Ketanserin 血清素引起的聚集扩张 血管 PAF拮抗剂 PAF 引起的聚集不定 Omega 3 脂肪酸 膜结构改变BP 轻度减少 维生素 E 与蛋白激酶有关预防内皮功能不良 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 抗血小板治疗的监测 v 监测方法有 血小板聚集实验 FPA 100 TEG VerifyNow Platelet Work TXB2 P 选择素 等 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial PlateletMapping Results P1 ADP AA KH MA 69 1 mm fibrin ogen thrombin activated platelets MA 10 0 mm fibrin ogen no platelet contribution MA 69 3 mm fibrin ogen ADP activated platelets MA 54 6 mm fibrin ogen AA activated platelets ADP 0 inhibition 100 aggregation AA 24 5 inhibition 75 5 aggregation Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial PlateletMapping Predicting bleeding risk KH ADP AA Fibrinogen Bleeding risk probably low ADP AA Fibrinogen KH Bleeding risk probably high Inhibition 50 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 抗血小板药副作用 v 出血 v 血小板减少 粒细胞减少 TTP 再障 v 胃肠不适 v 皮疹 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 理想的抗血小板药 v 快速起效 v 口服 v 可予期的反应 v 稳定的作用 v 作用可逆 v 抗栓效果和出血可控 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 现有抗血小板药的局限性 v 起效慢 v 抑制作用不强 v 反应变异大 v 不可逆性和出血危险 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial New Antiplatelet Agents v P 2 Y 12 antagonists Prasugrel AZD 6140 Cangrelor v Thrombin receptor antagonists SCH 530348 E 5555 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Prasugrel v 抑制 P 2 Y 12 v 药代动力学 迅速起效 2 h 不可逆的结合 v 与氯吡格雷激活的代谢途径不同 v 比氯吡格雷更有效的抑制 ADP 引 起的血小板激活 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 凝血酶受体拮抗剂 TRA SCH 530348 v 第一种此类药 v 口服 长效 v 阻断血小板 PAR 1 受体 v 不干扰纤维蛋白形成 v 对出血时间或 PT aPTT 无影响 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial 新 抗 血 小 板 药 v 血小板在动脉血栓中起关键作用 v 抗血小板药有意义的减少发病 但有局限性 v 根据对血小板激活的生物学的了解 有助于 开发更多新型抗血小板药 v 目前进行的研究将确定是否这些新药应用于 标准的治疗方案 Five weeks of practice ended in this way and my feelings can only be summed up in eight words although hard but very substantial bNfQiUlXo s v y0B3F6I9LdOgRjVmYq t w z1C4G7JbMePhTkWnZr u x A2E5H8KcNfRiUlXp s v y0C3F6IaLdOgSjVnYq t w z1D4G7JbMeQhTkWoZr u x B2E5H9KcNfRiUmXp s v y0C3F7IaLdPgSjVnYq t w A1D4G8JbNeQhTlWoZr u y B2E6H9KcOfRiUmXp s v z0C3F7IaMdPgSkVnYq t x A1D5G8JbNeQiTlWo r u y B3E6H9LcOfRjUmYp s w z0C4F7JaMdPhSkVnZq t x A2D5G8KbNeQiTlXo r v y B3E6I9LcOgRjUmYp t w z1C4F7JaMePhSkWnZq u x A2D5H8KbNfQiUlXo s v y0B3F6I9LdOgRjVmYp t w z1C4G7JaMePhTkWnZr u x A2E5H8KcNfQiUlXp s v y0B3F6IaLdOgSjVmYq t w z1D4G7JbMeQhTkWoZr u x A2E5H9KcNfRiUlXp s v y0C3F6IaLdPgSjVnYq t w A1D4G8JbMeQhTlWoZr u x B2E6H9KcOfRiUmXp s v z0C3F7IaMdPgSkVnYq t w A1D5G8JbNeQhTlWo r u y B2E6H9LcOfRjUmXp s w z0C4F7IaMdPhSkVnZq t x A2D5G8KbNeQiTlXo r v y B3E6H9LcOgRjUmYp s w z1C4F7JaMdPhSkWnZq u x A2D5H8KbNfQiTlXo s v y0B3E6I9LdOgRjVmYp t w z1C4G7JaMePhSkWnZr u x A2D5H8KcNfQiUlXo s v y0B3F6I9LdOgSjVmYq t w z1D4G7JbMePhTkWoZr u x A2E5H9KcNfRiUlXp s v y0C3F6IaLdOgSjVnYq t w z1D4G8JbMeQhTkWoZr u x B2E5H9KcOfRiUmXp s v z0C3F7IaLdPgSkVnYq t w A1D5G8NfRiUlXp s v y0C3F6IaLdOgSjVnYq t w z1D4G8JbMeQhTkWoZr u x B2E5H9KcOfRiUmXp s v z0C3F7IaLdPgSkVnYq t w A1D4G8JbNeQhTlWoZr u y B2E6H9KcOfRjUmXp s v z0C4F7IaMdPgSkVnZq t x A1D5G8KbNeQiTlWo r v y B3E6H9LcOfRjUmYp s w z0C4F7JaMdPhSkVnZq u x A2D5G8KbNfQiTlXo r v y0B3E6I9LcOgRjVmYp t w z1C4G7JaMePhSkWnZq u x A2D5H8KbNfQiUlXo s v y0B3F6I9LdOgRjVmYq t w z1C4G7JbMePhTkWnZr u x A2E5H8KcNfRiUlXp s v y0C3F6IaLdOgSjVmYq t w z1D4G7JbMeQhTkWoZr u x B2E5H9KcNfRiUmXp s v y0C3F7IaLdPgSjVnYq t w A1D4G8JbNeQhTlWoZr u x B2E6H9KcOfRiUmXp s v z0C3F7IaMdPgSkVnYq t x A1D5G8JbNeQiTlWo r u y B3E6H9LcOfRjUmYp s w z0C4F7JaMdPhSkVnZq t x A2D5G8KbNeQiTlXo r v y B3E6I9LcOgRjUmYp t w z1C4F7JaMePhSkWnZq u x A2D5H8KbNfQiUlXo w z0C4F7IaMdPhSkVnZq t x A2D5G8KbNeQiTlXo r v y B3E6I9LcOgRjUmYp t w z1C4F7JaMePhSkWnZq u x A2D5H8KbNfQiTlXo s v y0B3E6I9LdOgRjVmYp t w z1C4G7JaMePhTkWnZr u x A2E5H8KcNfQiUlXp s v y0B3F6IaLdOgSjVmYq t w z1D4G7JbMePhTkWoZr u x A2E5H9KcNfRiUlXp s v y0C3F6ePhTkWnZr u x A2E5H8KcNfQiUlXo w z1C4F7JaMdPhSkWnZq u x A2D5H8KbNfQiTlXo s v y0B3E6I9LdOgRjVmYp t w z1C4G7JaMePhTkWnZr u x A2D5H8KcNfQiUlXo s v y0B3F6I9LdOgSjVmYq t w z1D4G7JbMePhTkWoZr u x A2E5H9KcNfRiUlXp s v y0C3F6IaLdOgSjVnYq t w z1D4G8JbMeQhTkWoZr u x B2E5H9KcOfRiUmXp s v z0C3F7IaLdPgSkVnYq t w A1D5G8JbNeQhTlWo r u y B2E6H9KcOfRjUmXp s v z0C4F7IaMdPgSkVnZq t x A1D5G8KbNeQiTlWo r v y B3E6H9LcOgRjUmYp s w z1C4F7JaMdPhSkVnZq u x A2D5G8KbNfQiTlXo r v y0B3E6I9LcOgRjVmYp t w z1C4G7JaMePhSkWnZr u x A2D5H8KcNfQiUlXo s v y0B3F6I9LdOgRjVmYq t w z18KbNfQiTlXo r v y0B3E6I9LcOgRjVmYp t w z1C4G7JaMePhSkWnZr u x A2D5H8KbNfQiUlXo s v 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