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            <h1 id="seo-header">药理五：中枢神经系统药物之治疗退行疾病</h1>
            
            
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                <p>中枢神经系统退行性疾病，指由慢性进行性中枢神经组织退行性变性而产生的疾病。主要包括DA减少的帕金森病和ACh减少的阿尔茨海默症，以及其他遗传性的亨廷顿舞蹈症、肌萎缩侧索硬化症等。</p>
<h2 id="抗帕金森药"><a href="#抗帕金森药" class="headerlink" title="抗帕金森药"></a>抗帕金森药</h2><p>帕金森病是一种主要表现为进行性的锥体外系功能障碍的中枢神经系统退行性疾病。典型的症状是静止震颤、肌肉强直、运动迟缓和共济失调。病因多巴胺学说：锥体外系的黑质-纹状体通路多巴胺神经功能减弱，胆碱能神经功能相对占优，引起肌张力增高。另外还有氧化应激学说等</p>
<ul>
<li>锥体外系是指锥体系以外的影响和控制躯体运动的所有传导路径，包括大脑皮质（主要是躯体运动区和躯体感觉区）、纹状体、背侧丘脑、底丘脑、中脑顶盖、红核、黑质、脑桥核、前庭核、小脑和脑干网状结构等以及它们的纤维联系</li>
<li>皮质-纹状体系，纹状体是控制运动的重要调节中枢，有复杂的纤维联系，形成皮质-新纹状体-背侧丘脑-皮质环路、新纹状体-黑质环路、苍白球-底丘脑核环路；皮质-新纹状体-背侧丘脑-皮质环路可影响锥体束的躯体运动中枢的活动，新纹状体-黑质环路中的黑质神经细胞能产生和释放多巴胺，变性后纹状体内多巴胺含量降低，与帕金森病的发生有关，苍白球-底丘脑核环路对同侧苍白球反馈抑制，受损后对侧肢体出现大幅度颤搐</li>
<li>皮质-脑桥-小脑系，小脑综合脊髓本体感觉纤维的信息，一起协调和共济肌肉运动，受损导致共济失调，行走蹒跚、醉汉步态</li>
</ul>
<p>药物种类<br>左旋卡比苄丝肼，司来硝替溴隐停<br>利舒阿扑去吗啡，罗匹尼罗普拉索<br>金刚烷胺促释放，苯海扎品共拮抗</p>
<h3 id="多巴胺前体药"><a href="#多巴胺前体药" class="headerlink" title="多巴胺前体药"></a>多巴胺前体药</h3><p>左旋多巴帕金森，转化去甲肝性脑<br>年轻症，肌强直，运动困难较颤好<br>显效慢，持续长，药源帕金森无效<br>早胃肠，心血管；长期运动过多症<br>多不安，动不能，开关现象精神状<br>VB6，外脱羧，疗效降低不良增<br>吩噻嗪，利血平，合用药源帕金森  </p>
<h4 id="左旋多巴"><a href="#左旋多巴" class="headerlink" title="左旋多巴"></a>左旋多巴</h4><p>口服易吸收，主要分布在外周，仅1%进入中枢。外周L-DOPA被外周多巴脱羧酶转化为DA，外周作用增大，使副作用增多，为增加进入中枢的L-DOPA，可同时服用多巴脱羧酶抑制剂卡比多巴。</p>
<p>酪氨酸在羟化酶的作用下转变成左旋多巴，在脱羧酶作用下转变成多巴胺，经β羟化酶变成去甲肾、经儿茶酚-O-甲基转移酶变成3-O-甲基多巴。帕金森患者酪氨酸羟化酶减少，L-DOPA可以补充纹状体中多巴胺的不足而发挥作用。</p>
<p>治疗帕金森 轻症和年轻者效果好，改善肌强直和运动困难较肌震颤效果明显，显效慢，持续时间长</p>
<p>用于肝型脑病 使意识从昏迷转为清醒，不改善肝功能</p>
<p>早期反应，胃肠道反应，厌食、恶心、呕吐、腹痛、腹泻，由于多巴胺刺激延髓催吐化学感受区D2受体，可用D2受体阻断药多潘立酮（吗丁啉）改善；心血管反应，体位性低血压、心动过速或心律失常，可用β受体阻断药改善。</p>
<p>长期反应，运动过多症，不自主异常运动；波动症状，开（活动正常）关（严重的帕金森症状）现象；精神症状，与脑内多巴胺增多，兴奋中脑-皮质和中脑-边缘系统通路有关。</p>
<p>药物相互作用</p>
<p>禁止同时服用维生素B6，它使多巴胺脱羧酶辅酶，加速左旋多巴胺在外周脱羧，进入脑循环减少，使疗效降低，不良反应增多</p>
<p>不宜合用吩噻嗪类、利血平，它们通过阻断中枢DA受体和耗竭DA储存而引起药源性帕金森，拮抗左旋多巴的作用</p>
<p>禁止同时服用MAO-A抑制剂，它可阻断NA代谢，升高血中NA浓度，升高血压</p>
<h3 id="左旋多巴增效药"><a href="#左旋多巴增效药" class="headerlink" title="左旋多巴增效药"></a>左旋多巴增效药</h3><p>左旋多巴增效药，A苄B司C卡朋<br>卡比复方心宁美，苄丝左旋美多巴<br>托卡外周中枢抑，恩他外周抗母T<br>A：AADC，氨基脱羧酶抑制药<br>B：MAO-B，单胺氧化酶B抑制药<br>C：COMT，儿茶酚胺-O-甲基转移酶抑制药</p>
<h4 id="AADC"><a href="#AADC" class="headerlink" title="AADC"></a>AADC</h4><h5 id="卡比多巴（α-甲基多巴肼-洛得新）"><a href="#卡比多巴（α-甲基多巴肼-洛得新）" class="headerlink" title="卡比多巴（α-甲基多巴肼&#x2F;洛得新）"></a>卡比多巴（α-甲基多巴肼&#x2F;洛得新）</h5><p>外周脱羧酶抑制剂，不能通过血脑屏障，对中枢的脱羧酶无作用，单用无意义</p>
<p>与左旋多巴配伍用减少其在外周脱羧，增加进入中枢系统的量，提高疗效，减少副作用</p>
<p>复方制剂心宁美：卡比多巴：左旋多巴（1：4或1：10），使左旋多巴最适有效量比单独用时减少75%</p>
<h5 id="苄丝肼（羟苄丝肼-色丝肼）"><a href="#苄丝肼（羟苄丝肼-色丝肼）" class="headerlink" title="苄丝肼（羟苄丝肼&#x2F;色丝肼）"></a>苄丝肼（羟苄丝肼&#x2F;色丝肼）</h5><p>复方制剂美多巴为苄丝肼：左旋多巴（1：4）合用，作用同心宁美</p>
<h4 id="MAO-B"><a href="#MAO-B" class="headerlink" title="MAO-B"></a>MAO-B</h4><h5 id="司来吉兰（丙炔苯丙胺）"><a href="#司来吉兰（丙炔苯丙胺）" class="headerlink" title="司来吉兰（丙炔苯丙胺）"></a>司来吉兰（丙炔苯丙胺）</h5><p>选择性抑制MAO-B，抑制内&#x2F;外源性神经毒性物质产生，减少DA神经元损害，加强和延长左旋多巴的疗效，可与左旋多巴合用</p>
<p>慎与哌替啶、三环类抗抑郁药或其他MAO抑制药合用</p>
<h4 id="COMT"><a href="#COMT" class="headerlink" title="COMT"></a>COMT</h4><h5 id="硝替卡朋"><a href="#硝替卡朋" class="headerlink" title="硝替卡朋"></a>硝替卡朋</h5><p>不易通过血脑屏障，只抑制外周的COMT，增加纹状体左旋多巴的生物利用度</p>
<h5 id="托卡朋和恩他卡朋"><a href="#托卡朋和恩他卡朋" class="headerlink" title="托卡朋和恩他卡朋"></a>托卡朋和恩他卡朋</h5><p>托卡朋抑制外周和中枢的COMT，延长左旋多巴的半衰期，可引起肝损伤</p>
<p>恩他卡朋只抑制外周的COMT，生物利用度比托卡朋低</p>
<h3 id="多巴胺受体激动药"><a href="#多巴胺受体激动药" class="headerlink" title="多巴胺受体激动药"></a>多巴胺受体激动药</h3><p>溴隐亭，大剂量，黑质纹状帕金森<br>小剂量，结节漏，回乳反氯肢端大</p>
<h4 id="溴隐亭"><a href="#溴隐亭" class="headerlink" title="溴隐亭"></a>溴隐亭</h4><p>D2受体的强效激动剂，部分拮抗D1受体，对外周多巴胺受体、α受体有弱激动作用</p>
<p>小剂量对结节-漏斗处D2受体有选择性激动作用，减少催乳素释放，增大剂量可激动黑质-纹状体内D2受体，与左旋多巴合用疗效好</p>
<p>不良反应多，包括消化系统、心血管系统、运动功能障碍及精神系统症状等</p>
<h4 id="利修来得"><a href="#利修来得" class="headerlink" title="利修来得"></a>利修来得</h4><p>D2受体强激动剂，D1受体弱拮抗剂，改善运动功能障碍，减少严重的开关反应和左旋多巴引起的运动过多症</p>
<h4 id="罗匹尼罗和普拉克索"><a href="#罗匹尼罗和普拉克索" class="headerlink" title="罗匹尼罗和普拉克索"></a>罗匹尼罗和普拉克索</h4><p>选择性激动D2受体，对D1受体几乎没有作用，耐受性好，多作为帕金森早期治疗药物，不易引起开关反应和运动障碍</p>
<p>胃肠道反应较小，可引起直立性低血压、运动障碍、幻觉和精神错乱，特别是可引起突发性睡眠</p>
<h4 id="阿扑吗啡"><a href="#阿扑吗啡" class="headerlink" title="阿扑吗啡"></a>阿扑吗啡</h4><p>DA受体激动药，可改善严重的开关反应</p>
<p>长期用药可引起QT间期延长、肾功能损害和精神症状</p>
<h3 id="促多巴胺释放药"><a href="#促多巴胺释放药" class="headerlink" title="促多巴胺释放药"></a>促多巴胺释放药</h3><h4 id="金刚烷胺"><a href="#金刚烷胺" class="headerlink" title="金刚烷胺"></a>金刚烷胺</h4><p>促进DA进入脑循环，增加DA的合成和释放，并抑制神经末梢对DA的再摄取，有部分抗胆碱作用</p>
<p>缓解帕金森症状作用强于抗胆碱药</p>
<p>起效快，用药数天达最大疗效，持续短，连用6~8周后疗效减弱</p>
<p>长期用药引起下肢皮肤出现网状青斑，还可引起精神不安、失眠和运动失调等，癫痫患者禁用</p>
<h3 id="中枢性抗胆碱药"><a href="#中枢性抗胆碱药" class="headerlink" title="中枢性抗胆碱药"></a>中枢性抗胆碱药</h3><h4 id="苯海索（安坦）"><a href="#苯海索（安坦）" class="headerlink" title="苯海索（安坦）"></a>苯海索（安坦）</h4><p>中枢胆碱能受体阻断药，减弱黑质-纹状体通路中ACh作用</p>
<p>用于早期轻症帕金森患者，及不能耐受左旋多巴或左旋多巴禁忌症患者</p>
<p>抗精神病药物引起的帕金森综合征</p>
<h4 id="苯扎托品"><a href="#苯扎托品" class="headerlink" title="苯扎托品"></a>苯扎托品</h4><p>抗胆碱，还有抗组胺、局部麻醉作用和大脑皮质抑制作用</p>
<h2 id="治疗阿尔茨海默病的药"><a href="#治疗阿尔茨海默病的药" class="headerlink" title="治疗阿尔茨海默病的药"></a>治疗阿尔茨海默病的药</h2><p>阿尔茨海默症是一种和年龄高度相关、以进行性认知障碍和记忆力损害等表现为特征的中枢神经系统退行性疾病。表现为淀粉样蛋白沉积形成老年斑，异常的磷酸化Tau蛋白的聚集形成的神经纤维缠结。目前采用的治疗策略是增加中枢胆碱能神经功能，如乙酰胆碱酯酶抑制药和M胆碱受体激动剂是目前治疗AD的主要药物。</p>
<p>AD多奈利斯明，石杉碱甲加他敏<br>他克林，肝毒性，心肝肾病利斯明<br>加他敏，轻中度，老年记忆石碱甲<br>美金刚，非竞争，NMDA受体拮抗剂</p>
<h3 id="胆碱酯酶抑制药"><a href="#胆碱酯酶抑制药" class="headerlink" title="胆碱酯酶抑制药"></a>胆碱酯酶抑制药</h3><h4 id="他克林"><a href="#他克林" class="headerlink" title="他克林"></a>他克林</h4><p>第一代可逆性中枢性AChE抑制剂，可抑制血浆和组织中的AChE</p>
<p>可直接激动M胆碱受体和N胆碱受体，对M胆碱受体的亲和力是N胆碱受体的100倍；还可通过M1受体促进ACh释放</p>
<p>不良反应较多，包括肝毒性和消化道反应，由于其对肝毒性较大，目前已停用</p>
<h4 id="多奈哌齐"><a href="#多奈哌齐" class="headerlink" title="多奈哌齐"></a>多奈哌齐</h4><p>第二代可逆性中枢AChE抑制剂，使脑内ACh含量增加</p>
<p>与他克林相比，选择性高，半衰期较长，疗效好，且无肝毒性</p>
<p>用于轻至中度的AD患者</p>
<p>不良反应有胃肠道、心血管及神经系统反应，以及流感样胸痛、牙痛、失水尿失禁、呼吸困难、视物模糊等。</p>
<h4 id="利凡斯的明"><a href="#利凡斯的明" class="headerlink" title="利凡斯的明"></a>利凡斯的明</h4><p>第二代AChE抑制剂，可选择性抑制大脑皮质和海马中的AChE活性，而对纹状体、脑桥以及心脏中的AChE活性抑制作用较弱</p>
<p>可明显改善AD患者的认知功能障碍</p>
<p>安全、耐受性好、不良反应少，且无外周作用</p>
<p>适用于伴有心脏、肝及肾等疾病的AD患者</p>
<p>常见的不良反应有恶心、呕吐、眩晕和腹泻等，服药一段时间后大多可自行消失。</p>
<h4 id="加兰他敏"><a href="#加兰他敏" class="headerlink" title="加兰他敏"></a>加兰他敏</h4><p>第二代AChE抑制剂，对神经元中的AChE有高度选择性</p>
<p>其疗效与他克林相似，但无肝毒性，用药6~8周效果开始明显</p>
<p>用于轻、中度的AD患者</p>
<p>不良反应主要为胃肠道反应（治疗初期2~3周），稍后即消失</p>
<h4 id="石杉碱甲"><a href="#石杉碱甲" class="headerlink" title="石杉碱甲"></a>石杉碱甲</h4><p>可逆性、高度选择性的AChE抑制剂</p>
<p>具有显著改善AD患者记忆和认知功能的作用</p>
<p>用于老年性记忆功能减退及各型AD患者</p>
<p>常见不良反应有恶心、头晕、多汗、腹痛、视物模糊等，一般可自行缓解，严重者可用阿托品拮抗</p>
<h4 id="美曲膦酯"><a href="#美曲膦酯" class="headerlink" title="美曲膦酯"></a>美曲膦酯</h4><p>唯一以无活性前药形式存在的AChE抑制药，服用数小时后转化为活性的代谢产物而发挥持久疗效</p>
<p>可同时改善AD患者的行为和认知功能</p>
<p>适用于治疗轻、中度AD</p>
<p>不良反应较少，偶见腹泻、下肢痉挛、鼻炎等症状，继续使用会自行消失</p>
<h3 id="NMDA受体非竞争性拮抗药"><a href="#NMDA受体非竞争性拮抗药" class="headerlink" title="NMDA受体非竞争性拮抗药"></a>NMDA受体非竞争性拮抗药</h3><h4 id="美金刚（美金刚胺）"><a href="#美金刚（美金刚胺）" class="headerlink" title="美金刚（美金刚胺）"></a>美金刚（美金刚胺）</h4><p>特异性、非竞争性NMDA受体拮抗剂，可降低谷氨酸引起的兴奋性毒性</p>
<p>本药能显著改善AD患者的认知功能，可改善中至重度AD患者的动作能力，认知障碍和社会行为</p>
<p>不良反应为眩晕、不安、头重、口干等</p>
<h3 id="M胆碱受体激动药"><a href="#M胆碱受体激动药" class="headerlink" title="M胆碱受体激动药"></a>M胆碱受体激动药</h3><p>M胆碱受体激动药可以增强胆碱能神经功能，逆转Aβ诱导的神经元损伤，减少Tau蛋白的磷酸化</p>
<h4 id="呫诺美林"><a href="#呫诺美林" class="headerlink" title="呫诺美林"></a>呫诺美林</h4><p>选择性M1受体激动药，对M2、M3、M4、M5受体作用很弱</p>
<p>易透过血脑屏障，大脑皮质和纹状体摄取率较高</p>
<p>可改善AD患者的认知和行为功能</p>
<p>易引起胃肠道及心血管方面的不良反应，可选择经皮肤给药</p>
<h4 id="沙可美林"><a href="#沙可美林" class="headerlink" title="沙可美林"></a>沙可美林</h4><p>相对选择性M1受体激动药</p>
<p>安全、耐受性好，可改善AD患者的认知功能</p>
<p>常见的不良反应有轻微出汗等</p>

                
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        }
        if (CONFIG.anchorjs.placement === 'left') {
          anchors.options.class = 'anchorjs-link-left';
        }
        anchors.add(res.join(', '));
      }
    });
  });
</script>


<script>
  Fluid.utils.createScript('https://lib.baomitu.com/fancybox/3.5.7/jquery.fancybox.min.js', function() {
    Fluid.plugins.fancyBox();
  });
</script>


  <script>Fluid.plugins.imageCaption();</script>

  <script  src="/js/local-search.js" ></script>


<!-- 主题的启动项，将它保持在最底部 -->
<!-- the boot of the theme, keep it at the bottom -->
<script  src="/js/boot.js" ></script>


  <noscript>
    <div class="noscript-warning">Blog works best with JavaScript enabled</div>
  </noscript>
<!-- hexo injector body_end start -->
  <script defer src="/theme-inject/timeliness.js"></script>
<!-- hexo injector body_end end --></body>
</html>