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            <h1 id="seo-header">【迁移】药理一：传出神经系统药物之胆碱受体</h1>
            
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                    Last updated on March 19, 2024 pm
                  
                
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                <p>传出神经分植物神经和运动神经，前者支配心肌、平滑肌和腺体等，后者支配骨骼肌。植物神经分交感和副交感(副交感节前纤维常在迷走神经内走行)，交感兴奋时效应器表现为应急时的状态，副交感兴奋时效应器表现为睡眠时的状态。</p>
<p><img src="https://img.limour.top/2023/09/01/64f1a938bbb3e.webp" srcset="https://jscdn.limour.top/gh/Limour-dev/Sakurairo_Vision/load_svg/inload.svg" lazyload alt=""></p>
<h2 id="ACh、AChE相关药">ACh、AChE相关药</h2>
<p>拟胆碱药分两类，兴奋受体抑制酶<br>
匹罗卡品作用眼，外用治疗青光眼<br>
阿托交替芸香碱，防止虹膜晶状粘<br>
贝胆碱、腹气胀，兴奋泌尿和胃肠<br>
新斯地明抗酯酶，主治重症肌无力<br>
术后腹胀尿潴留，小心胆碱能危象<br>
毒扁豆碱毒性大，作用眼科降眼压<br>
解磷定解N症状，百虫遇碱敌敌畏，乐果中毒碘无效</p>
<p>M样作用<br>
扩张血管降血压，负性三连心动缓<br>
兴奋膀胱逼尿肌，括约舒张胃肠蠕<br>
缩瞳降压调痉挛，泪腺唾液汗泌增</p>
<p>N样作用<br>
骨骼肌，神经节，N样受体有烟碱</p>
<p>毛果芸香碱（匹罗卡品）毛开头，所以是M受体激动剂，具有副交感样作用，一般用于滴眼。放松时，看近物比较多，比如刷手机，需要避免近处亮光刺激眼睛，因此瞳孔括约肌上的M受体激动时瞳孔会收缩，此时前房角会开大，有利于房水从内部的小梁网排出，降低眼内压，常用1%滴眼液来治疗青光眼。同时看近物需要更高的晶状体屈光度，所以会调节痉挛，睫状肌上的M受体激动、睫状肌收缩，悬韧带两端靠近而松弛，让晶状体回弹。由于所有腺体上都长M受体，所有毛果芸香碱不小心通过内眦的鼻泪管进入鼻腔、然后进入口腔时，会有大量鼻涕和唾液分泌，所以也能用来治疗口腔干燥，不过如果是治疗青光眼，则需要压迫内眦，避免此副作用。如果全身给药，肠道、支气管等内脏平滑肌上也长M受体，会促进胃肠蠕动引起痉挛、诱发哮喘，心肌上长M受体，会降低心率和血压，中枢神经长M受体，会激活和维持皮层觉醒。</p>
<p>阿毛是一对，所以阿托品是M受体拮抗剂，可以起到与毛果芸香碱相反的作用，交替使用可以瞳孔扩缩交替，让虹膜保持运动状态，避免虹膜与晶状体粘连。如果阿托品中毒，则用毛果芸香碱来解毒。</p>
<p>氯贝胆碱为M胆碱受体激动剂，对胃肠道和膀胱平滑肌的选择性较高，对心血管系统影响小，所以常用于术后腹气胀，胃张力缺乏症及胃潴留等的治疗。</p>
<p>新斯的明能抑制AChE，同时还具有直接激动骨骼肌上的N2受体的作用，因此主要用于治疗重症肌无力，同时也能用于治疗抑制N2受体的非去极化肌松药中毒和筒箭毒中毒。如果过量，则产生胆碱能危象，持续激活化学门控离子通道N2受体，肌束震颤，较长时间后，其他电压门控离子通道由于不能复极化而无法复活，当失活数量太多时，将产生肌麻痹，而呼吸肌麻痹后果严重。此外因为抑制AChE、激动M受体，胃肠道、支气管、膀胱、心脏、腺体、眼睛，所以可以治疗术后肠胀气、尿潴留、阵发性室上性心动过速、青光眼、解救阿托品中毒，同时机械性肠/尿路梗阻、支气管哮喘禁用。季铵类化合物，脂溶性差，不易穿过血脑屏障。依酚氯胺常用于诊断。多奈哌齐常用于中枢阿尔兹海默症。</p>
<p>毒扁豆碱具有与新斯的明相似的可逆性抑制胆碱酯酶的作用，同时易于通过血脑屏障，对中枢神经系统，小剂量兴奋，大剂量抑制。因此毒性大，只外用来降低眼压。</p>
<p>有机磷酸酯类急性中毒，除了M样症状和N样症状外，还有中枢症状，早期兴奋中枢，表现为躁动不安、幻觉、谵妄、惊厥，后期抑制，头晕、乏力、嗜睡、昏迷，晚期呼吸循环衰竭，呼吸中枢和心血管中枢抑制</p>
<p>有机磷酸酯类治疗，首先清除尚未吸收的药物，生理盐水或小苏打洗胃、但是敌百虫（美曲膦酯）遇碱会水解成敌敌畏、对硫磷遇高锰酸钾会氧化成对氧磷，用肥皂水清洗皮肤，然后解毒，联用阿托品和解磷定，由于解磷定的半衰期非常短，需要重复给药，同时维持气道通畅、给氧、抗休克。注意事项 阿托品给药需要一直到阿托品化，瞳孔扩大、面色潮红、皮肤干燥、口干、心率加快；复活剂在碱性溶液中会水解成氰化物，不能与碱性药物并用，且对中毒超3d的老化AChE无效。</p>
<p>M样作用的扩血管主要来自激动血管内皮细胞上的M3受体，其释放NO，从而使周围平滑肌舒张，血压下降，此时会有短暂的反射性心率增加，之后作用于心肌M受体，负性三连。</p>
<h2 id="胆碱受体阻断药">胆碱受体阻断药</h2>
<p>阿托品<br>
莨菪碱类阿托品，抑制腺体平滑肌<br>
瞳孔扩大眼压升，调节麻痹心率快<br>
大量改善微循环，中枢兴奋须防范<br>
作用广泛有利弊，应用注意心血管<br>
临床用途有奇效，胃肠绞痛立即缓<br>
抑制分泌麻醉前，虹膜睫状体发炎，散瞳配镜眼底检<br>
防止虹晶粘，能治心动缓<br>
感染休克解痉挛，有机磷中毒它首选<br>
禁用前列青光眼，幽门梗阻也禁选<br>
阿托中毒解救药，毒扁豆碱地西泮</p>
<p>莨菪碱类<br>
莨菪碱类阿托品，阻断M–抗胆碱<br>
尿不出去和便秘，老年痴呆青光眼<br>
作用广泛有利弊，最好不用老年人<br>
镇静显著东莨碱，能抗晕动是特点<br>
帕金森病麻醉前，只是不用它点眼<br>
感染休克山莨碱，内脏平滑肌绞痛</p>
<p>N受体<br>
美卡拉明神经节，两类骨骼肌松弛<br>
琥珀胆、肌束颤，没有神经节阻断<br>
除极化、N结合，烧伤高钾心脏停<br>
碱分解、勿硫喷，呼吸麻痹抗生素<br>
筒箭毒碱正相反，缓慢持久组胺释</p>
<p>阿托品可以抑制腺体M受体，胃酸分泌影响不明显，汗腺、唾液腺支气管腺分泌减少，可以用来治疗流涎、盗汗和麻醉前给药防止支气管痰液阻塞。正在发热的患者使用会降低出汗散热的能力，导致高热。</p>
<p>阿托品散瞳，眼压升高，阻断睫状肌，调节麻痹，因此可以阿毛一起用于虹膜炎，但阿托品常用的还是眼底检查和验光配镜。散瞳和调节麻痹的效果可以持续一周，所以验光后会长时间视力模糊。解除迷走神经对心脏的抑制作用，可以正性三变。因此首选用于治疗各种缓慢性心律失常，如窦性心动过缓、房室传导阻滞。会用心悸的副作用、可能诱发心梗。低剂量会心率短暂性轻度减慢。</p>
<p>能解除内脏平滑肌痉挛状态，因此和阿片类（中枢止痛但会加剧外周平滑肌痉挛，阿托品解除痉挛）合用可以治疗胃肠道、膀胱、肾、胆的绞痛。禁用于便秘、肠胀气、尿潴留、前列腺肥大。</p>
<p>当大剂量使用阿托品时（与阻断M受体无关），也能解除血管平滑肌痉挛，扩张血管（直接和间接两种方式，间接的比如汗腺分泌减少后，散热需要通过皮肤血管扩张来代偿），改善微循环，增加重要脏器的血供，适用于感染性休克。休克时皮肤苍白湿冷、而阿托品可以使面色潮红、手脚温暖。也会使中枢先兴奋后抑制，先多言、谵妄、幻觉、惊厥，然后呼吸抑制。</p>
<ul>
<li>唯有阿托品，可解除迷走对心脏的抑制而治疗缓慢型心律失常</li>
<li>利多卡因、苯妥英钠，可用于治疗强心苷中毒时的快速型心律失常</li>
<li>普萘洛尔，首选用于窦性心动过速</li>
<li>奎尼丁，可将地高辛从组织中置换出来，升高其血药浓度而加重中毒</li>
</ul>
<p>东莨菪碱容易穿过血脑屏障，对中枢的作用强，有中枢抗胆碱作用和中枢镇静作用，可以抑制前庭神经，治疗帕金森和晕动病。对腺体的抑制作用比阿托品强，加上具有中枢镇静的效果，所以常用于麻醉前给药。容易出现中枢不良反应、谵妄、幻觉、欣快，进而导致滥用。对心血管、眼的作用弱。</p>
<p>山莨菪碱（6542）很难穿过血脑屏障，对眼、腺体、中枢作用弱，主要具有强大的血管平滑肌和内脏平滑肌的痉挛作用，主治感染性休克、内脏绞痛，补足血容量的前提下，可用于其他休克。有面色潮红、便秘、肠胀气、尿潴留的副作用。</p>
<p>阿托品的徒子徒孙（合成代用品）有合成扩瞳药，后马托品、托吡卡胺、环喷托酯、尤卡托品，较阿托品起效快，持续时间短，名字都带托，起效一点不托；合成解痉药，异丙托溴铵、溴丙胺太林（普鲁本辛）、贝那替嗪（胃复康）。另，各种西平，如派仑西平，可以选择阻断胃壁细胞上的M1受体，抑制胃酸分泌。</p>
<p><img src="https://img.limour.top/2023/09/01/64f1a94b9d91f.webp" srcset="https://jscdn.limour.top/gh/Limour-dev/Sakurairo_Vision/load_svg/inload.svg" lazyload alt=""></p>
<p>N1受体主要在神经节上，阻断剂有经典的美卡拉明，六甲双铵，速效短效的樟磺咪芬，既阻断交感，又阻断副交感。美卡拉明阻断交感，血压下降，麻醉时用来控制血压。阻断副交感，阻断M样症状，口干、视力模糊、便秘、肠胀气、尿潴留。</p>
<p>去打老虎，因此琥珀胆碱事去极化型肌松药，激动N2受体，持久去极化，使骨骼肌长期处于不应期状态。因此短暂肌束颤动后起效快，时间短，易于控制。静注用于短时操作，如气管插管、消化道镜检，静滴用于较长的手术。不能用新斯的明解救，因为琥珀年代久远，不新了。由于持续去极化，肌肉钾离子流出，血钾会升高。呼吸肌麻痹可能窒息、肌束震颤会疼、血钾升高抑制心脏。禁用于白内障、青光眼（眼外骨骼肌短暂收缩，升高眼压）、晶体摘除手术和血钾升高的烧伤、脑血管意外、恶性高热等。与氨基糖苷类抗生素或多黏菌素B合用，后者阻断神经肌肉接头，协同易致呼吸肌麻痹。</p>
<p>而捡裤子穿的筒箭毒碱阻断N2受体，竞争性抑制受体，使骨骼肌不能收缩。肌松作用慢而持久，先松弛眼部和头部的小肌肉，然后是颈部，到四肢、躯干，再面、舌、咽喉和咀嚼肌，最后是肋间肌、膈肌，另，对喉头、气管作用强。用于大手术的辅助麻醉。用新斯的明解救。此外，还具有促组胺释放和神经节阻滞的作用，诱发皮疹、支气管痉挛、血压下降。</p>

                
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