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            <h1 id="seo-header">药理四：中枢神经系统药物之抗癫痫和抗惊厥</h1>
            
            
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                <p>癫痫是一种突然发生的、阵发性、短暂性、反复发作的大脑功能障碍，发作时常伴有脑电的异常。惊厥是中枢神经系统过度兴奋的一种症状，表现为突发性的全身性或局限性肌群强直性或阵挛性抽搐。常用的抗惊厥药物包括巴比妥类、苯二氮䓬类中的部分药物、水合氯醛及硫酸镁。</p>
<p>癫痫小发作，首选乙琥胺，抑T钙通道<br>局限发作大发作，卡马西平加二苯<br>皮质激素肌阵挛，持续状态用安定<br>慢加剂量停药渐，坚持用药防骤停<br>苯妥英钠<br>大仑丁，小无效，三坐舌咽室性常<br>膜稳定，阻钠钙，口慢不肌静脉给，小十一级大零级<br>碱刺激，齿龈增，低钙贫血男女症，补D补钙补叶酸<br>卡马西平<br>单局性，三舌咽，锂盐无效躁狂症<br>阻滞钠，升GABA，骨髓抑制肝损伤<br>丙戊酸钠<br>大小并，顽固性，GABA生成代谢少<br>抑制钠T钙通道，广谱抗癫痫病药<br>硫酸镁<br>效用主要看途径，泻下利胆用口服<br>消炎去肿外热敷，注射用药抑中枢<br>高压危象急救用，子痫抽搐破伤风  </p>
<h2 id="乙琥胺"><a href="#乙琥胺" class="headerlink" title="乙琥胺"></a>乙琥胺</h2><p>口服吸收完全，血浆蛋白结合率低，儿童半衰期30小时，成人半衰期40~50小时</p>
<p>抑制丘脑T型钙通道，抑制3Hz异常放电，高浓度可抑制钠钾泵和GABA转氨酶</p>
<p>治疗小发作的首选药（对其他类型无效），抗戊四氮引起的阵挛性惊厥，提高电惊厥阈值</p>
<p>毒性低，但可引起肠胃道反应、中枢神经系统症状（精神病患者慎用）</p>
<p>偶见粒细胞缺乏症，严重者发生再生障碍性贫血。</p>
<h2 id="苯妥英钠（大仑丁）"><a href="#苯妥英钠（大仑丁）" class="headerlink" title="苯妥英钠（大仑丁）"></a>苯妥英钠（大仑丁）</h2><p>口服吸收不规则，起效慢，不宜作肌内注射。静脉注射用于治疗癫痫的持续状态。药物消除速率与血药浓度密切相关，＜10μg&#x2F;mg按一级动力学消除，半衰期为20小时；大于10μg&#x2F;mg按零级动力学消除，半衰期＞60小时。有条件监测血药浓度，调整剂量。</p>
<p>具有膜稳定作用，阻止病灶放电向正常组织扩散，主要通过：阻断电压依赖性Na+通道，阻断电压依赖性Ca2+通道，影响钙调素激酶系统。</p>
<p>抗癫痫 抗大发作、局限性发作首选，但对小发作无效，甚至会增加发作次数</p>
<p>治疗中枢性疼痛综合征及外周神经痛：三叉神经、坐骨神经、舌咽神经痛</p>
<p>抗心律失常 室性，特别是强心苷中毒</p>
<p>局部刺激、齿龈增生</p>
<p>神经系统反应 20 共济失调，40 精神错乱， 50 昏迷</p>
<p>血液系统反应 巨幼红细胞性贫血</p>
<p>骨骼系统反应 低钙血症</p>
<p>过敏反应</p>
<p>其他反应 男性乳房增大、女性多毛症、淋巴结肿大、致畸，久用突然停药可致癫痫发作加剧</p>
<p>药物相互作用 肝药酶诱导剂、血浆蛋白</p>
<h2 id="卡马西平（酰胺咪嗪）"><a href="#卡马西平（酰胺咪嗪）" class="headerlink" title="卡马西平（酰胺咪嗪）"></a>卡马西平（酰胺咪嗪）</h2><p>口服吸收缓慢、不规则，血浆蛋白质结合率为75%<del>80%，单次给药半衰期为15</del>20小时。</p>
<p>与苯妥英钠相似，治疗浓度阻滞Na+通道，阻止放电扩散，并可提高脑内GABA浓度，增强其中枢抑制作用。</p>
<p>抗癫痫 为有效的广谱抗癫痫药，治疗单纯性局限性发作和大发作的首选之一，还可抗复合性局限性发作和小发作</p>
<p>对中枢性疼痛（三叉、舌咽）的疗效优于苯妥英钠</p>
<p>对锂盐无效的躁狂症有效</p>
<p>常见眩晕、视物模糊、恶心、呕吐、共济失调、手指震颤、水钠潴留等不良反应</p>
<p>严重不良反应有骨髓抑制、过敏反应（肝损伤）、心律失常等</p>
<p>药物相互作用 肝药酶诱导剂</p>
<h2 id="苯巴比妥（鲁米那）"><a href="#苯巴比妥（鲁米那）" class="headerlink" title="苯巴比妥（鲁米那）"></a>苯巴比妥（鲁米那）</h2><p>既能抑制病灶的异常放电又能阻止放电扩散，主要通过：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；阻断突触前膜Ca2+摄取，减少Ca2+依赖性神经递质的释放；较高浓度可阻断Na+和Ca2+通道。</p>
<p>可用于癫痫的大发作和持续状态，对单纯的局限性发作和精神运动性发作也有效，但对小发作效果差</p>
<p>中枢抑制作用强，不作为长期维持用药</p>
<p>用药初期易出现嗜睡、精神萎靡</p>
<p>长期使用产生耐受性</p>
<p>药物相互作用 肝药酶诱导剂</p>
<p>药物相互作用 肝药酶诱导剂</p>
<h2 id="扑米酮（去氧苯巴比妥）"><a href="#扑米酮（去氧苯巴比妥）" class="headerlink" title="扑米酮（去氧苯巴比妥）"></a>扑米酮（去氧苯巴比妥）</h2><p>体内代谢为苯巴比妥和苯乙基丙二酰胺</p>
<p>对部分性发作和大发作疗效好（不能耐受二苯的大发作），对小发作无效</p>
<p>常见的不良反应包括中枢症状和血液系统毒性</p>
<h2 id="丙戊酸钠"><a href="#丙戊酸钠" class="headerlink" title="丙戊酸钠"></a>丙戊酸钠</h2><p>口服吸收完全迅速，血浆蛋白质结合率高，半衰期约为15小时</p>
<p>阻止放电扩散，使GABA生成增加、代谢减少，增加GABA能神经突触后抑制作用，抑制Na+通道和T型Ca2+通道，抑制3Hz异常放电</p>
<p>广谱抗癫痫药，尤其对小发作效果好，但有肝毒性，不作为小发作的首选药</p>
<p>是大发作合并小发作时的首选药，对其他药物不能控制的顽固性癫痫也有效</p>
<p>消化系统症状 恶心、呕吐、腹痛等</p>
<p>肝毒性</p>
<p>偶见皮疹、脱发、血小板减少及聚集障碍</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>可以阻止放电扩散，但不能消除病灶的异常放电</p>
<p>地西泮首选用于癫痫持续状态，静脉注射起效快，但需要注意其对呼吸的抑制作用</p>
<p>硝西泮主要用于癫痫的小发作，肌阵挛性发作、婴儿痉挛</p>
<p>氯硝西泮抗癫痫谱广，但易耐受，久用突然停药会加剧癫痫发作</p>
<h2 id="氟桂利嗪"><a href="#氟桂利嗪" class="headerlink" title="氟桂利嗪"></a>氟桂利嗪</h2><p>口服易吸收，半衰期19~22天，血浆蛋白质结合率高（99%）</p>
<p>可以阻断T型和L型Ca2+通道及电压依赖性Na+通道</p>
<p>对局限性发作、大发作效果好</p>
<p>常见不良反应是困倦、体重增加。</p>
<h2 id="拉莫三嗪"><a href="#拉莫三嗪" class="headerlink" title="拉莫三嗪"></a>拉莫三嗪</h2><p>口服吸收完全，生物利用度98%，血浆蛋白质结合率55%，半衰期12.6小时</p>
<p>阻断电压依赖性Na+通道，阻止病灶的异常放电</p>
<p>多与其他抗癫痫药合用，治疗难治性癫痫</p>
<p>中枢系统反应 头痛、头晕、嗜睡、视物模糊、复视、共济失调</p>
<p>胃肠道反应 恶性、呕吐、便秘</p>
<p>偶见皮肤水肿及弥散性血管内凝血</p>
<h2 id="托吡酯"><a href="#托吡酯" class="headerlink" title="托吡酯"></a>托吡酯</h2><p>可以阻断电压依赖性Na+通道，增强GABA活性，并抑制谷氨酸介导的兴奋作用</p>
<p>主要用于局限性发作和大发作，特别是辅助治疗难治性癫痫</p>
<p>常见的不良反应是中枢系统反应，孕妇慎用</p>
<h2 id="硫酸镁"><a href="#硫酸镁" class="headerlink" title="硫酸镁"></a>硫酸镁</h2><p>不同给药途径产生不同的药理作用，口服泻下和利胆作用，外用热敷消炎去肿，注射产生全身作用</p>
<p>可能是由于Mg2+可以特异性地与Ca2+竞争Ca2+受体，拮抗Ca2+作用，从而发挥肌松及降压作用，而Mg2+作用于中枢神经系统，则引起感觉及意识丧失。</p>
<p>主要用于子痫、破伤风等惊厥，也常用于高血压危象。</p>
<p>注射给药的安全范围窄，血镁过高会引发呼吸抑制、血压骤降和心搏骤停</p>
<p>肌腱反射消失是呼吸抑制的先兆，连续注射需监测</p>
<p>急性中毒时应立即进行人工呼吸，注射氯化钙和葡萄糖酸钙解毒</p>

                
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