失眠癥的藥物治療教學培訓課件

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**醫(yī)科大學臨床藥學教研室《臨床藥物治療學》課程臨床藥學專業(yè)大四學年第二學期--失眠癥的藥物治療藥物咨詢室的故事e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434難以入睡醒得早易焦慮反反復復。。。。診斷：失眠癥處方：右匹克隆1mg睡前口服用藥史：自行服用過艾司唑侖，但白天精神差問題：詢問右匹克隆和艾司唑侖一樣嗎？可否長期服用？思考問題？e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434什么是失眠癥？失眠癥的治療原則？治療藥物如何選用？失眠，焦慮定義是以入睡困難和（或）睡眠維持困難所致的睡眠質(zhì)量或數(shù)量達不到正常生理需求而影響日間社會功能的一種主觀體驗最常見的睡眠障礙性疾患失眠癥e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434失眠癥的病因e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E84341.心理因素生活和工作中的各種不愉快事件造成焦慮、抑郁、緊張時可引起3.睡眠節(jié)律改變夜班和白班頻繁變動飛行時差引起生物鐘節(jié)律變化2.環(huán)境因素環(huán)境嘈雜、空氣污濁居住擁擠或突然改變睡眠環(huán)境4.日常生活因素饑餓、疲勞、性興奮等酒精、咖啡、茶葉攝入，睡前飲水過多等5.藥物因素藥物依賴或戒斷癥狀使用中樞神經(jīng)興奮性藥物6.疾病各類精神疾病大多伴有睡眠障礙軀體疾病致“共病性失眠”1.入睡困難2.睡眠維持障礙，易醒3.早醒，醒后不能再睡4.睡眠質(zhì)量差，晨醒后仍困倦失眠癥的臨床表現(xiàn)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434總體目標明確病因，改善睡眠質(zhì)量和（或）增加有效睡眠時間恢復社會功能，提高患者的生活質(zhì)量減少或消除與失眠相關的軀體疾病避免藥物干預帶來的負面效應1.一般治療原則睡眠衛(wèi)生教育放松治療，行為治療認知行為治療治療原則e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434非苯二氮卓類藥物（non-BZDs)首選治療失眠t1/2短，次日殘余效應最大程度降低苯二氮卓類藥物（BZDs)褪黑素受體激動劑抗抑郁藥物食欲素受體拮抗劑0102030405e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434藥物治療原則個體化：考慮癥狀的針對性，權(quán)衡獲益與風險鎮(zhèn)靜、抗焦慮、肌松和抗驚厥作用首選焦慮性失眠不能耐受、藥物依賴患者的替代治療調(diào)節(jié)睡眠-覺醒周期治療抑郁和焦慮障礙而改善睡眠癥狀蘇沃雷生FDA批準用于治療成人失眠非苯二氮卓類藥物（non-BZDs)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434藥物達峰時間(h)半衰期(h)適應癥成人睡前口服劑量（mg)CYP3A4代謝佐匹克隆1.5-25入睡困難或睡眠維持障礙3.75-7.5CYP3A4抑制劑如克拉霉素會抑制non-BZDs類藥物代謝，血藥濃度↑CYP3A4誘導劑利福平降低其血藥濃度，療效↓右佐匹克隆1-1.561-3唑吡坦0.5-32.4（0.7-3.5）1.75-10緩釋片6.25-12.5扎來普隆≤10.7-1.4入睡困難5-20苯二氮卓類藥物（BZDs)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434藥物達峰時間(h)半衰期(h)適應癥成人睡前口服劑量（mg)指南推薦三唑侖(一精)0.2-0.51.5-5.5入睡困難0.125-0.25推薦艾司唑侖310-24入睡困難或睡眠維持障礙1-2-替馬西泮1.2-1.63.5-18.47.5-30推薦夸西泮2-348-1207.5-15-氟西泮1.5-4.548-12015-30-注意事項其他如阿普唑侖、勞拉西泮和地西泮，該類藥物有依賴性，長期應用后，停藥可能發(fā)生撤藥癥狀禁用于妊娠或哺乳期婦女，肝腎功能損害者、阻塞性睡眠呼吸暫停綜合征患者及重度通氣功能缺損者除勞拉西泮和替馬西泮外，均通過CYP3A4代謝酒精和中樞鎮(zhèn)靜類藥物將增加中樞抑制效應e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434苯二氮卓類藥物（BZDs)雷美替胺合并睡眠呼吸障礙的失眠患者安全有效無藥物依賴性，無戒斷癥狀，適用于長期失眠褪黑素參與調(diào)節(jié)睡眠-覺醒周期，可以改善時差變化引起的癥狀、睡眠時相延遲綜合征和晝夜節(jié)律失調(diào)性睡眠障礙。褪黑素緩釋片雷美替胺普通褪黑素臨床證據(jù)有限，不宜作為失眠的常規(guī)用藥褪黑素受體激動劑e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434選擇性5-羥色胺再攝取抑制劑（SSRIs）：氟伏沙明抑制褪黑素的降解，唯一具有鎮(zhèn)靜作用的SSRIs改善抑郁和焦慮患者的夜間睡眠質(zhì)量SSRIs多賽平小劑量（3-6mg/d）專一性抗組胺改善成年和老年慢性失眠患者的睡眠狀況耐受性好、無戒斷反應三環(huán)類米氮平：小劑量使用曲唑酮：治療睡眠障礙、重度睡眠呼吸暫停綜合征，催眠藥物停藥后的失眠反彈其他5-羥色胺和去甲腎上腺素再攝取抑制劑（SSRIs）：文拉法辛和度洛西汀治療抑郁和焦慮狀態(tài)改善睡眠抗抑郁藥物e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB7874501A1FFE158C4981707381814BCC4D9A8E3554438DEE4FBCF5A5B4D2A8B0989AB57E8BAC65EBA777C8CACD7C08D5A4E48B332027CF30873CDB8E302B5A8F1C58E5042125DD4E342DB0421EDA32B628FCAEA7840C3D74710D6F09227C40AEBC1D5006CC1E8434SNRIs失眠癥藥物治療總結(jié)e7d195523061f1c01ef2b70529884c179423570dbaad84926380ABC1F97BAEF0C8FC051856578EAB787450