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            <h1 id="seo-header">药理三：中枢神经系统药物之镇静催眠</h1>
            
            
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                <p>镇静催眠药通过增强GABA功能或作用于GABA受体而抑制中枢神经系统，随着剂量的增加，依次产生镇静、催眠、抗惊厥、抗癫痫和中枢性肌松作用。常用的镇静催眠药包括苯二氮䓬类、巴比妥类和非苯二氮䓬类。其中苯二氮䓬类还有抗焦虑、抗抑郁的作用。</p>
<p>镇静催眠巴比妥，苯二氮䓬首安定<br>抗惊抗癫抗焦虑，中枢肌松地西泮<br>剂量不同效有异，过量中毒快抢救<br>洗胃补液又给氧，碱化尿液促排泄<br>特效解毒氟马尼，特异位点拮抗剂<br>苯二口服肌注慢，消除短效三唑仑<br>硫喷妥钠静脉麻，水和氯醛胃肠激<br>硝西泮，肌阵挛，扎来佐匹唑吡坦，主要用作镇催眠。</p>
<p>成瘾性：苯二氮䓬类&gt;依匹克隆&gt;唑吡坦&gt;扎来普隆</p>
<h2 id="苯二氮䓬类"><a href="#苯二氮䓬类" class="headerlink" title="苯二氮䓬类"></a>苯二氮䓬类</h2><p>苯二氮䓬类可以分长效、中效、短效三类，长效的地西泮在肝脏代谢生成活性代谢产物去甲西泮，后者进一步代谢产生短效的奥沙西泮，最后形成葡萄糖醛酸结合物经肾脏排泄。西泮中长效的有地西泮、氟西泮、夸西泮，短效的有奥沙西泮，其他的劳拉西泮、替马西泮、氯硝西泮为中效；唑仑除三唑仑是短效外，阿普唑仑和艾司唑仑是中效；氯氮卓是长效。</p>
<p>苯二氮䓬类口服吸收迅速完全，肌内注射吸收缓慢且不规则；脂溶性高，极易透过生物屏障，血浆蛋白结合率高，代谢物往往仍有活性。</p>
<p>苯二氮䓬类的中枢作用主要与增强中枢抑制性神经递质GABA功能有关：苯二氮䓬类药物与GABAA受体复合物上的苯二氮䓬类受点结合，促进GABA与GABAA受体结合，增加Cl-通道开放，促进Cl-内流，神经细胞超极化，增强GABA的中枢抑制作用。</p>
<p>镇静催眠作用 主要延长非快速眼动睡眠（NREMS）的第2期，对快速眼动睡眠（REMS）影响小，停药后很少出现反跳、多梦现象。</p>
<ul>
<li>根据脑电图的特点，NREM睡眠可以分四期，I期为入睡期，脑电波表现为低幅θ波和β波，脑电波趋于平坦，很快过渡到II期</li>
<li>II期为浅睡期，脑电波呈持续0.5~1s的σ波（α波的变异，频率稍快，幅度稍低）及若干κ复合波（δ波和σ波的复合），随后睡眠进入III期</li>
<li>III期是中度睡眠期，脑电波中出现高幅δ波。当δ波在脑电波中超过50%时，睡眠便进入IV期，即深度睡眠期。III期和IV期统称为δ睡眠，在人类，合称慢波睡眠。</li>
<li>慢波睡眠之后，脑电的渐进性高幅低频变化出现逆转，呈现与觉醒时相似的不规则β波，表现为皮质活动的去同步化，但在行为上却表现为睡眠状态。在REM期，机体各种感觉进一步减弱，肌紧张减弱，交感神经活动进一步降低，下丘脑体温调节功能明显减退，表明其睡眠深度要比慢波睡眠更深。</li>
<li>REM睡眠期间，脑内蛋白质合成加快，脑的耗氧量和血流量增多，生长激素分泌则减少。REM睡眠与幼儿神经系统的成熟和建立新的突触联系密切有关，能促进学习与记忆以及精力恢复。</li>
</ul>
<p>抗惊厥、抗癫痫作用 用于辅助治疗破伤风、子痫、小儿高热惊厥、药物中毒性惊厥等。地西泮时治疗癫痫持续状态的首选药物。</p>
<p>中枢性肌松作用 具有较强的肌松作用，可缓解动物去大脑僵直，也可减轻人大脑损伤所致的肌肉僵硬，可用于内镜检查所致肌痉挛。</p>
<p>抗焦虑作用 小剂量即可显著改善紧张、忧虑、激动、失眠等症状。主要用于焦虑症。</p>
<p>其他 较大剂量可致暂时记忆缺失，抑制肺泡换气功能，降低血压，减慢心率。</p>
<p>副作用 常见服药次日出现出现嗜睡、头晕、乏力、记忆力下降、共济失调。</p>
<p>久用产生耐受性和依赖性。</p>
<p>与其他中枢抑制药、乙醇合用，中枢抑制作用增强。</p>
<p>过量可致昏迷和呼吸抑制。用氟马西尼解毒（苯二氮䓬受体结合位点的拮抗药）。</p>
<h2 id="巴比妥类"><a href="#巴比妥类" class="headerlink" title="巴比妥类"></a>巴比妥类</h2><p>巴比妥类药物根据消除的半衰期的长短可分为：长效的苯巴比妥和巴比妥，中效的戊巴比妥、异戊巴比妥，短效的司可巴比妥，超短效的硫喷妥钠。</p>
<p>口服、肌注均易吸收，碱化尿液可促进排出。</p>
<p>作用机制与苯二氮䓬类相似，结合GABAA受体上的巴比妥类受体位点，促进GABA与GABAA受体结合，延长Cl-通道开放时间，产生中枢抑制作用。此外，巴比妥类药物还可抑制谷氨酸受体。产生中枢抑制作用。</p>
<p>镇静催眠 引起非生理性睡眠，缩短REMS。久用突然停药后，REMS时相反跳性延长，出现焦虑、失眠、多梦。“反跳”是依赖性原因之一。</p>
<p>抗惊厥、抗癫痫作用 用于癫痫大发作和持续状态，也可用于小儿高热、破伤风、子痫、脑膜炎、中枢兴奋性药中毒。</p>
<p>麻醉 硫喷妥钠用于静脉麻醉。</p>
<p>后遗作用 催眠剂量的巴比妥类在次日晨仍可出现头晕、困倦、精神不振和定向障碍等。</p>
<p>久用产生成瘾性。</p>
<p>肝药酶诱导剂，能加速其他药物的代谢。</p>
<p>中等剂量可导致呼吸抑制，通过碱化尿液、维持呼吸和循环功能、应用中枢兴奋药解救</p>
<h2 id="非苯二氮䓬类"><a href="#非苯二氮䓬类" class="headerlink" title="非苯二氮䓬类"></a>非苯二氮䓬类</h2><p>能选择性结合BZ受体亚单位，不影响认知、学习和记忆，起效快，对正常睡眠结构影响小。</p>
<ul>
<li><p>依匹克隆（唑比酮）</p>
</li>
<li><p>具有镇静、抗焦虑、抗惊厥和肌松作用</p>
</li>
<li><p>失眠者服用后入睡快，增加深睡眠，醒后感觉良好</p>
</li>
<li><p>无明显的耐药和停药反跳现象</p>
</li>
<li><p>唑吡坦（思诺思）</p>
</li>
<li><p>镇静催眠作用较强，抗焦虑、中枢性肌松和抗惊厥作用弱</p>
</li>
<li><p>缩短睡眠潜伏期，延长睡眠总时间，减少觉醒次数</p>
</li>
<li><p>常规剂量不产生耐药性，停药后无反跳</p>
</li>
<li><p>中毒时用氟马西尼解毒</p>
</li>
<li><p>扎来普隆</p>
</li>
<li><p>具有镇静、抗焦虑、抗惊厥和肌松作用</p>
</li>
<li><p>有效缩短入睡时间，适用于入睡困难的短期治疗，后遗作用小</p>
</li>
<li><p>耐受性良好，无依赖性。</p>
</li>
<li><p>水合氯醛</p>
</li>
<li><p>不影响REMS，停药后无反跳现象</p>
</li>
<li><p>大剂量有抗惊厥作用</p>
</li>
<li><p>对胃肠道有强烈刺激作用</p>
</li>
<li><p>久服也可引起耐受性、成瘾性</p>
</li>
<li><p>大剂量对心脏有抑制作用</p>
</li>
<li><p>丁螺环酮</p>
</li>
<li><p>5-HT1A受体部分激动剂，与GABAA系统无直接关系。</p>
</li>
<li><p>主要用于抗焦虑和伴有焦虑的失眠、抑郁症等</p>
</li>
<li><p>不良反应有头晕、头痛和胃肠功能紊乱</p>
</li>
<li><p>无明显的生理依赖性和成瘾性</p>
</li>
</ul>

                
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