7种苯二氮䓬类药物临床应用细则,这篇帮你总结好了!

2022-04-16 网络 网络

苯二氮䓬类药物主要用于焦虑、失眠、兴奋激越、紧张综合征、癫痫、肌痉挛、酒精戒断及

苯二氮䓬类药物主要用于焦虑、失眠、兴奋激越、紧张综合征、癫痫、肌痉挛、酒精戒断及外科术前的辅助用药等。
 

1、苯二氮䓬类作用机制

1苯二氮䓬类药物通过升高抑制性神经递质γ-氨基丁酸(GABA)与受体的亲和力从而完成与GABAA受体的特异性结合,而非直接激活受体。
2GABA与GABAA受体亲和力增加促进氯离子通道开放,使GABA的中枢抑制效应增强。
3GABAA受体有6种α亚单位(α1、α2、α3、α4、α5、α6),是与苯二氮䓬受体结合的区域,不同的α亚单位与苯二氮䓬类药物亲和性不同,因此不同的药物具有不同的药物代谢动力学特征、产生不同的临床效应。
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4苯二氮䓬类药物受体广泛存在于中枢神经系统,包括皮层、丘脑、海马及纹状体等,所以在介导抗焦虑、镇静和抗惊厥作用的同时,可能会引起顺行性遗忘,影响记忆功能。

2、苯二氮䓬类药物特点

1地西泮
  • 地西泮属于长效、中等强度苯二氮䓬类药物。
  • 地西泮具有镇定、催眠、抗焦虑、抗惊厥和肌肉松弛作用,目前多用于治疗酒精依赖的戒断反应以及癫痫持续状态(注:已较少应用于助眠)。
  • 口服吸收迅速、完全,主要在肝脏代谢(CYP450代谢酶为2C19、3A4),经肾排泄。
  • 生物利用度为100%,达峰时间为0.5-1.5h,半衰期为26-50h(半衰期长,重复给药可在体内积聚)。
  • 地西泮用于老年人的安全性较低,可能引起跌倒,增加外伤风险。
  • 应注意卟啉病及肝、肾功能不全者慎用。
  • 地西泮能透过胎盘屏障,且能进入母乳,孕妇及哺乳期女性禁用。
(2)奥沙西泮
  • 奥沙西泮为地西泮的主要代谢产物。
  • 奥沙西泮口服吸收好,但吸收速度较慢,达峰时间为 1.5-2h,生物利用度为99%,半衰期为5-12h。
  • 奥沙西泮更适用于无需立即入睡的患者,对改善后半程睡眠障碍疗效更佳
  • 奥沙西泮不经过CYP450代谢,经由肾脏排出,故对肝功能不全者相对安全,且在体内无蓄积作用,代谢不受年龄影响,不容易与其他药物发生相互作用。
  • 奥沙西泮的半衰期接近正常睡眠周期,所以服药后第二天大多无头晕感,宿醉反应少,安全性高,适用于老年人,且患者使用的满意度较高。
  • 起效慢、不容易蓄积等特点也使其成瘾风险较其他苯二氮䓬类药物更小。
  • 在药物对认知功能的影响方面,虽然普遍认为苯二氮䓬类药物对认知功能尤其记忆功能存在影响,但研究发现奥沙西泮优于其他苯二氮䓬类药物。
3劳拉西泮
  • 劳拉西泮是一种高效能、中短效的苯二氮䓬类药物。
  • 劳拉西泮口服吸收完全,达峰时间约2h,生物利用度为99%,半衰期为10-20h。
  • 劳拉西泮不经过CYP450代谢,经由肾脏排出,但严重肝功能不全患者其半衰期可能延长,故慎用。
  • 劳拉西泮在各种苯二氮䓬类药物中抗焦虑作用最强是地西泮的2-5倍,通常治疗焦虑症的日剂量为:2-6mg,分2-3次口服。
  • 劳拉西泮可有效地控制癫痫持续状态,是持续性全身性强直、阵挛性发作等初期控制的首选药物
  • 在精神科临床治疗中,劳拉西泮常用于辅助抗精神病药物治疗急性兴奋激越等。虽然在联合用药的情况下可减少抗精神病药物用量,但在精神分裂症的长期治疗中其作用尚无定论。
4艾司唑仑
  • 艾司唑仑为中等半衰期的苯二氮䓬类药物。
  • 艾司唑仑平均半衰期为10-24h,口服后吸收良好,生物利用度为 90%,达峰时间<2h,主要在肝脏代谢(CYP450代谢酶为3A4),经肾排泄。
  • 当肾小球滤过率低于30 ml/min时,艾司唑仑须谨慎使用。
  • 艾司唑仑较其他苯二氮䓬类药物安全性较好,出现反跳性失眠的情况较少,可作为睡眠障碍患者初期苯二氮䓬类用药的选择当疗效欠佳时可更换其他药物。
5咪达唑仑
  • 咪达唑仑为短效苯二氮䓬类药物。
  • 咪达唑仑吸收迅速,根据给药途径的不同,达峰时间从20-60min不等,半衰期为1-3h。
  • 咪达唑仑在中枢神经系统可与苯二氮䓬受体高度特异性结合,从而产生抑制作用,在临床麻醉及各种镇静治疗中被广泛应用
  • 咪达唑仑经肝代谢(CYP450代谢酶为3A4、3A5),有明显的首过效应,口服生物利用度较低,肌注生物利用度约为90%。
  • 咪达唑仑具有短效、水溶性等特点,能迅速进入中枢神经系统,迅速再分布,但作用时间短,需要持续地注入才能维持镇静。
  • 咪达唑仑较其他苯二氮䓬类药物引起遗忘的作用更强。
  • 咪达唑仑静脉注射时应注意其呼吸抑制作用,虽然低剂量(0.075mg/kg) 给药的中枢抑制作用不明显,但该药抑制效果的出现较为突然,因此当剂量接近或超过此剂量时建议在有监护及复苏的设备条件下谨慎使用。
  • 咪达唑仑对心血管系统影响较小,可安全应用于低心排量患者。
(6)阿普唑仑
  • 阿普唑仑为高效价、中效(中等半衰期)的苯二氮䓬类药物。
  • 阿普唑仑口服吸收好,生物利用度>80%,达峰时间为1-2h,半衰期为11-15h,经肝代谢(CYP450代谢酶为3A4),以原始药物和代谢产物的形式经尿液排出。
  • 阿普唑仑常用于焦虑障碍0.2mg起始即可有效控制焦虑急性发作症状。
  • 对睡眠障碍中延长睡眠时间也有效果,不易产生宿醉感,但停用时常会引起焦虑症状反跳,所以在用药剂量及用药时长上须慎重。
  • 高剂量、长期(2-24 mg/d,用药8周-3年) 应用产生戒断综合征的可能性大,表现为严重的焦虑、烦躁、紧张感及失眠。突然停药、减药过快、剂量过大是产生戒断反应的主要原因。建议减药速度需慢,每3d减量不超过1mg,减药期维持2-3月,并监测戒断症状发生。
  • 卟啉病及肝、肾功能不全者慎用。
7氯硝西泮
  • 氯硝西泮为长效、中等强度苯二氮䓬类药物。
  • 氯硝西泮口服易吸收,生物利用度>80%,达峰时间为1~4 h,半衰期24~56 h,经肝脏完全代谢(CYP450 代谢酶为3A4),由肾脏排出。
  • 氯硝西泮能透过胎盘屏障,可分布于母乳,且其具有致畸作用,故而妊娠及哺乳期女性禁用。
  • 氯硝西泮抗惊厥作用强,可用于各种类型癫痫发作、肌阵挛相关的异常运动。
  • 氯硝西泮在抗焦虑方面具有优势对于急性发作的焦虑,如惊恐障碍,低剂量 (0.5 mg) 使用即可产生快速缓解作用。
  • 氯硝西泮半衰期长,可在体内蓄积,困倦不良反应常见。
  • 患者有时有宿醉感,老年人应慎用以减少跌倒的发生风险。

参考文献:
(1)药品说明书.
(2)刘飞,陆峥. 苯二氮䓬类药物临床使用专家共识要点解读. 世界临床药物, 2018, 39(10):716-720.
来源:临床用药评价

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  3. [GetPortalCommentsPageByObjectIdResponse(id=1763918, encodeId=8e241e639184f, content=<a href='/topic/show?id=8a978e05523' target=_blank style='color:#2F92EE;'>#苯二氮䓬类药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87055, encryptionId=8a978e05523, topicName=苯二氮䓬类药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=566c37602221, createdName=ms7474195563676018, createdTime=Sat May 07 13:21:47 CST 2022, time=2022-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1835920, encodeId=e3a91835920e5, content=<a href='/topic/show?id=cfdc22e893f' target=_blank style='color:#2F92EE;'>#临床应用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22789, encryptionId=cfdc22e893f, topicName=临床应用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Fri Jan 20 10:21:47 CST 2023, time=2023-01-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213972, encodeId=b57112139e2d6, content=时刻学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sun Apr 24 20:51:44 CST 2022, time=2022-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213771, encodeId=16fc1213e7188, content=坚持学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sat Apr 23 22:55:13 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211756, encodeId=711b1211e56f3, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/e8b96fdba070433da10cd357c0646807/28bf16f46e314caaad8396c0c7df7a04.jpg, createdBy=adb15496357, createdName=仁术2021, createdTime=Sat Apr 16 22:39:01 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497588, encodeId=f774149e588f6, content=<a href='/topic/show?id=7d8e8e05288' target=_blank style='color:#2F92EE;'>#苯二氮䓬#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87052, encryptionId=7d8e8e05288, topicName=苯二氮䓬)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea2d9344205, createdName=smallant2005, createdTime=Mon Apr 18 11:21:47 CST 2022, time=2022-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211792, encodeId=c2271211e92f6, content=不错,很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=18a58120318, createdName=ms3000000481721339, createdTime=Sun Apr 17 04:33:30 CST 2022, time=2022-04-17, status=1, ipAttribution=)]
    2022-04-24 杨海东

    时刻学习

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1763918, encodeId=8e241e639184f, content=<a href='/topic/show?id=8a978e05523' target=_blank style='color:#2F92EE;'>#苯二氮䓬类药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87055, encryptionId=8a978e05523, topicName=苯二氮䓬类药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=566c37602221, createdName=ms7474195563676018, createdTime=Sat May 07 13:21:47 CST 2022, time=2022-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1835920, encodeId=e3a91835920e5, content=<a href='/topic/show?id=cfdc22e893f' target=_blank style='color:#2F92EE;'>#临床应用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22789, encryptionId=cfdc22e893f, topicName=临床应用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Fri Jan 20 10:21:47 CST 2023, time=2023-01-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213972, encodeId=b57112139e2d6, content=时刻学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sun Apr 24 20:51:44 CST 2022, time=2022-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213771, encodeId=16fc1213e7188, content=坚持学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sat Apr 23 22:55:13 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211756, encodeId=711b1211e56f3, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/e8b96fdba070433da10cd357c0646807/28bf16f46e314caaad8396c0c7df7a04.jpg, createdBy=adb15496357, createdName=仁术2021, createdTime=Sat Apr 16 22:39:01 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497588, encodeId=f774149e588f6, content=<a href='/topic/show?id=7d8e8e05288' target=_blank style='color:#2F92EE;'>#苯二氮䓬#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87052, encryptionId=7d8e8e05288, topicName=苯二氮䓬)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea2d9344205, createdName=smallant2005, createdTime=Mon Apr 18 11:21:47 CST 2022, time=2022-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211792, encodeId=c2271211e92f6, content=不错,很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=18a58120318, createdName=ms3000000481721339, createdTime=Sun Apr 17 04:33:30 CST 2022, time=2022-04-17, status=1, ipAttribution=)]
    2022-04-23 杨海东

    坚持学习

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1763918, encodeId=8e241e639184f, content=<a href='/topic/show?id=8a978e05523' target=_blank style='color:#2F92EE;'>#苯二氮䓬类药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87055, encryptionId=8a978e05523, topicName=苯二氮䓬类药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=566c37602221, createdName=ms7474195563676018, createdTime=Sat May 07 13:21:47 CST 2022, time=2022-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1835920, encodeId=e3a91835920e5, content=<a href='/topic/show?id=cfdc22e893f' target=_blank style='color:#2F92EE;'>#临床应用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22789, encryptionId=cfdc22e893f, topicName=临床应用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Fri Jan 20 10:21:47 CST 2023, time=2023-01-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213972, encodeId=b57112139e2d6, content=时刻学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sun Apr 24 20:51:44 CST 2022, time=2022-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1213771, encodeId=16fc1213e7188, content=坚持学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210313/9df56058b3964a8cac82563f95f0389d/c1b478592e8e4463bef44d32712e98fd.jpg, createdBy=ea905324251, createdName=杨海东, createdTime=Sat Apr 23 22:55:13 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211756, encodeId=711b1211e56f3, content=不错,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/e8b96fdba070433da10cd357c0646807/28bf16f46e314caaad8396c0c7df7a04.jpg, createdBy=adb15496357, createdName=仁术2021, createdTime=Sat Apr 16 22:39:01 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1497588, encodeId=f774149e588f6, content=<a href='/topic/show?id=7d8e8e05288' target=_blank style='color:#2F92EE;'>#苯二氮䓬#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87052, encryptionId=7d8e8e05288, topicName=苯二氮䓬)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea2d9344205, createdName=smallant2005, createdTime=Mon Apr 18 11:21:47 CST 2022, time=2022-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1211792, encodeId=c2271211e92f6, content=不错,很有帮助, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=18a58120318, createdName=ms3000000481721339, createdTime=Sun Apr 17 04:33:30 CST 2022, time=2022-04-17, status=1, ipAttribution=)]
    2022-04-16 仁术2021

    不错,学习了。

    0

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    2022-04-17 ms3000000481721339

    不错,很有帮助

    0