失眠症的药物治疗教学培训课件

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**医科大学临床药学教研室《临床药物治疗学》课程临床药学专业大四学年第二学期--失眠症的药物治疗药物咨询室的故事e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434难以入睡醒得早易焦虑反反复复。。。。诊断：失眠症处方：右匹克隆1mg睡前口服用药史：自行服用过艾司唑仑，但白天精神差问题：询问右匹克隆和艾司唑仑一样吗？可否长期服用？思考问题？e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434什么是失眠症？失眠症的治疗原则？治疗药物如何选用？失眠，焦虑定义是以入睡困难和（或）睡眠维持困难所致的睡眠质量或数量达不到正常生理需求而影响日间社会功能的一种主观体验最常见的睡眠障碍性疾患失眠症e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434失眠症的病因e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E84341.心理因素生活和工作中的各种不愉快事件造成焦虑、抑郁、紧张时可引起3.睡眠节律改变夜班和白班频繁变动飞行时差引起生物钟节律变化2.环境因素环境嘈杂、空气污浊居住拥挤或突然改变睡眠环境4.日常生活因素饥饿、疲劳、性兴奋等酒精、咖啡、茶叶摄入，睡前饮水过多等5.药物因素药物依赖或戒断症状使用中枢神经兴奋性药物6.疾病各类精神疾病大多伴有睡眠障碍躯体疾病致“共病性失眠”1.入睡困难2.睡眠维持障碍，易醒3.早醒，醒后不能再睡4.睡眠质量差，晨醒后仍困倦失眠症的临床表现e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434总体目标明确病因，改善睡眠质量和（或）增加有效睡眠时间恢复社会功能，提高患者的生活质量减少或消除与失眠相关的躯体疾病避免药物干预带来的负面效应1.一般治疗原则睡眠卫生教育放松治疗，行为治疗认知行为治疗治疗原则e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434非苯二氮卓类药物（non-BZDs)首选治疗失眠t1/2短，次日残余效应最大程度降低苯二氮卓类药物（BZDs)褪黑素受体激动剂抗抑郁药物食欲素受体拮抗剂0102030405e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434药物治疗原则个体化：考虑症状的针对性，权衡获益与风险镇静、抗焦虑、肌松和抗惊厥作用首选焦虑性失眠不能耐受、药物依赖患者的替代治疗调节睡眠-觉醒周期治疗抑郁和焦虑障碍而改善睡眠症状苏沃雷生FDA批准用于治疗成人失眠非苯二氮卓类药物（non-BZDs)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434药物达峰时间(h)半衰期(h)适应症成人睡前口服剂量（mg)CYP3A4代谢佐匹克隆1.5-25入睡困难或睡眠维持障碍3.75-7.5CYP3A4抑制剂如克拉霉素会抑制non-BZDs类药物代谢，血药浓度↑CYP3A4诱导剂利福平降低其血药浓度，疗效↓右佐匹克隆1-1.561-3唑吡坦0.5-32.4（0.7-3.5）1.75-10缓释片6.25-12.5扎来普隆≤10.7-1.4入睡困难5-20苯二氮卓类药物（BZDs)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434药物达峰时间(h)半衰期(h)适应症成人睡前口服剂量（mg)指南推荐三唑仑(一精)0.2-0.51.5-5.5入睡困难0.125-0.25推荐艾司唑仑310-24入睡困难或睡眠维持障碍1-2-替马西泮1.2-1.63.5-18.47.5-30推荐夸西泮2-348-1207.5-15-氟西泮1.5-4.548-12015-30-注意事项其他如阿普唑仑、劳拉西泮和地西泮，该类药物有依赖性，长期应用后，停药可能发生撤药症状禁用于妊娠或哺乳期妇女，肝肾功能损害者、阻塞性睡眠呼吸暂停综合征患者及重度通气功能缺损者除劳拉西泮和替马西泮外，均通过CYP3A4代谢酒精和中枢镇静类药物将增加中枢抑制效应e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434苯二氮卓类药物（BZDs)雷美替胺合并睡眠呼吸障碍的失眠患者安全有效无药物依赖性，无戒断症状，适用于长期失眠褪黑素参与调节睡眠-觉醒周期，可以改善时差变化引起的症状、睡眠时相延迟综合征和昼夜节律失调性睡眠障碍。褪黑素缓释片雷美替胺普通褪黑素临床证据有限，不宜作为失眠的常规用药褪黑素受体激动剂e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434选择性5-羟色胺再摄取抑制剂（SSRIs）：氟伏沙明抑制褪黑素的降解，唯一具有镇静作用的SSRIs改善抑郁和焦虑患者的夜间睡眠质量SSRIs多赛平小剂量（3-6mg/d）专一性抗组胺改善成年和老年慢性失眠患者的睡眠状况耐受性好、无戒断反应三环类米氮平：小剂量使用曲唑酮：治疗睡眠障碍、重度睡眠呼吸暂停综合征，催眠药物停药后的失眠反弹其他5-羟色胺和去甲肾上腺素再摄取抑制剂（SSRIs）：文拉法辛和度洛西汀治疗抑郁和焦虑状态改善睡眠抗抑郁药物e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434SNRIs失眠症药物治疗总结e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB787450