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      當前位置: 首頁 > 執業藥師 > 執業藥師備考資料 > 2019執業藥師《藥學專業知識一》講義及例題:第十一章

      2019執業藥師《藥學專業知識一》講義及例題:第十一章

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      發布時間:2019年06月10日 10:05:34 來源:環球網校 點擊量:

      【摘要】《藥學專業知識一》是2019年執業藥師資格考試的考試科目之一,目前2019執業藥師藥學專業知識一考試大綱及教材都已公布,環球網校執業藥師頻道為大家帶來2019執業藥師《藥學專業知識一》講義及例題:第十一章,幫助大家學習掌握該科目。

      相關推薦:2019執業藥師《藥學專業知識一》講義及例題匯總

      第十一章 常用藥物的結構特征與作用

      第一節 精神與中樞神經系統疾病用藥

      鎮靜與催眠藥:苯二氮(艸卓)類與非苯二氮(艸卓)類

      抗癲癇藥物:巴比妥類與二苯并氮(艸卓)類

      抗精神病藥物:吩噻嗪類、其他三環類、其他類

      抗抑郁藥:NE重攝取抑制劑與5-HT重攝取抑制劑

      鎮痛藥:天然生物堿類、哌啶類、氨基酮類、其他合成類

      一、鎮靜與催眠藥:苯二氮(艸卓)類和非苯二氮(艸卓)類

      1.苯二氮(艸卓)類:基本結構含A、B、C三個環,如地西泮。

      (1)A環和C環:引入吸電子取代基,活性增強。如硝西泮、氯硝西泮、氟西泮和氟地西泮。

      (2)B環:引入羥基可增加極性,易與葡萄糖醛酸結合排出體外,更加安全,如奧沙西泮。

      (3)1,2位并上三唑環:代謝穩定性增加;且與受體的親和力提高,活性顯著增加。如艾司唑侖、阿普唑侖和三唑侖。

      2.非苯二氮(艸卓)類:唑吡坦(咪唑并吡啶結構);佐匹克隆(吡咯酮結構,右旋體為艾司佐匹克隆)。

      二、抗癲癇藥物:巴比妥類和二苯并氮(艸卓)類

      1.巴比妥類:環丙二酰脲(巴比妥酸)。

      巴比妥酸無治療作用,5,5-二取代類化合物才有效。

      戊巴比妥、司可巴比妥:中、短效型催眠藥。

      硫噴妥:2位碳上氧原子被硫取代,解離度增大,脂溶性增加。起效快,但持續時間短。

      苯妥英鈉:飽和代謝動力學。

      磷苯妥英鈉:苯妥英的磷酸酯類前藥,肌肉注射吸收迅速。

      2.二苯并氮(艸卓)類:卡馬西平(最初治療三叉神經痛)、奧卡西平(卡馬西平的10-酮基衍生物)。

      三、抗精神病藥物:吩噻嗪類、其他三環類和其他結構類

      1.吩噻嗪類:基本結構硫氮雜蒽母核。氯丙嗪,治療以興奮癥為主的精神病,主要副作用是錐體外系作用。患者服用氯丙嗪后,遇光會分解,故皮膚會產生紅疹,稱光毒化過敏反應。

      結構改造:

      抗精神病活性與2位取代基的吸電子性能成正比。

      2位乙酰基取代可降低毒性,如乙酰丙嗪作用弱,毒性低。

      吩噻嗪母核氮原子以哌嗪側鏈取代,如奮乃靜、氟奮乃靜。

      氟奮乃靜的作用時間只能維持一天,其長鏈脂肪酸酯類的前藥庚氟奮乃靜,可使藥物作用時間延長。

      2.其他三環類藥物

      吩噻嗪(硫氮雜蒽)環上N被C取代,得到噻噸(硫雜蒽)。

      氯普噻噸、珠氯噻醇、氟哌噻噸。

      將吩噻嗪分子的硫原子或氮原子以甲亞胺基取代,得到二苯并二氮(艸卓)類和二苯并硫氮(艸卓)類藥物,代表藥物氯氮平和氯噻平。

      3.其他結構藥物

      利培酮和齊拉西酮:運用駢合原理設計的非經典抗精神病藥。

      四、抗抑郁藥

      2類:去甲腎上腺素重攝取抑制劑和5-羥色胺重攝取抑制劑。

      1.去甲腎上腺素重攝取抑制劑

      (1)二苯并氮(艸卓)類:丙米嗪、氯米帕明。

      (2)二苯并庚二烯類:阿米替林及其活性代謝產物去甲替林。

      (3)二苯并噁嗪類:多塞平。兩個幾何異構體:E型(trans-)和Z型(cis-)。85:15的E型和Z型異構體混合物。E型抑制去甲腎上腺素重攝取活性強;Z型抑制5-羥色胺重攝取活性強。

      2.5-羥色胺(5-HT)重攝取抑制劑:氟西汀及去甲氟西汀。

      氟西汀口服吸收良好,生物利用度為100%。去甲氟西汀的半衰期很長,為330小時,藥物蓄積及排泄緩慢。肝病和腎病患者需考慮氟西汀的用藥安全問題。

      舍曲林、氯伏沙明和氟伏沙明。

      文拉法辛:屬5-羥色胺/去甲腎上腺素重攝取抑制劑,小劑量主要抑制5-HT重攝取,大劑量對5-HT和NE重攝取均有抑制作用。

      西酞普蘭與艾司西酞普蘭(西酞普蘭的S-對映體)。

      帕羅西汀:顯示非線性藥動學特征。

      五、鎮痛藥:按來源分天然和合成鎮痛藥。

      嗎啡受體活性部位模型,主要結合點:①一個負離子部位;②一個適合芳環的平坦區;③一個與烴基鏈相適應的凹槽部位。

      1.天然生物堿及其類似物

      嗎啡:具菲環結構,由5個環稠合而成。立體構象呈T型。有效構型左旋嗎啡,具酸堿性。臨床用鹽酸鹽。

      可待因:嗎啡3位羥基發生甲基化。鎮痛活性弱,具鎮咳作用。

      二乙酰嗎啡(海洛因):嗎啡3、6位羥基同時酯化。

      烯丙嗎啡和納洛酮:嗎啡N-甲基被烯丙基、環丙基甲基或環丁基甲基等取代。

      羥考酮:阿片受體純激動劑。無劑量限制,鎮痛作用無封頂效應,只受限于不能耐受的副作用。

      控釋片:治療中、重度疼痛患者。雙相吸收模式:速釋相和緩釋相。減少服藥次數,患者順應性好,有利疼痛控制。

      藥代特征:由CYP3A代謝成去甲羥考酮和由CYP2D6代謝成羥嗎啡酮,代謝物主要經腎臟排泄。老年人的AUC大。女性血漿藥物濃度比男性高。

      2.哌啶類

      哌替啶:4-苯基哌啶類鎮痛藥,酯鍵特殊性,非前藥。可被血漿中的酯酶水解生成無鎮痛活性的哌替啶酸。

      芬太尼:4-苯氨基哌啶類鎮痛藥,親脂性高,易通過血-腦屏障,起效快,作用強。作用時間短。

      阿芬太尼(易透過血-腦屏障)、舒芬太尼(輔助麻醉藥)、瑞芬太尼(非前體藥物)。

      3.氨基酮類(二苯基庚酮類或苯丙胺類):美沙酮。

      4.其他合成鎮痛藥:布桂嗪、曲馬多(幾無成癮性)。

      1 2 3 4

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