临床麻醉学课件：第八章肌松药的临床应用.ppt

* Let us consider now what causes this fade process. Although still a matter of debate, the fade process is thought to be linked to the prejunctional nicotinic receptors. The prejunctional nicotinic receptors are labeled N3. They differ from the postjunctional nicotinic receptors. Stimulation of N1 receptors on the postjunctional membrane by released acetylcholine, produces the endplate potential and thereby triggers the train of events leading to contraction. Block of these receptors produces depression of amplitude of the postjunctional responses. Stimulation of N3 receptors by released acetylcholine (ACh) enhances mobilization and thereby enables availability of stored ACh to keep pace with the demand for it. Mobilization may include movement of vesicles to the release sites (or active zones), refilling of recently discharged vesicles with freshly synthesized acetylcholine, transfer of acetylcholine from reserve vesicles to active vesicles and renewed availability of release sites. Block of these receptors therefore produces the fade phenomena because the availability of transmitter can no longer match the requirement for it. [You can see on the diagram that there are prejunctional N1 nicotinic receptors. It appears that under physiological conditions these are totally protected from ACh by acetylcholinesterase (the enzyme inactivating ACh).] * TOF=0.7，抬头5s，伸舌，握力好。临床多以此值作为NMT恢复的指标或全麻后拔除气管导管的指征，但扔存在药物的残余作用 * DBS的肌收缩衰减较TOF更明显 ，神经肌肉存在非去极化阻滞时，第二组强直刺激出现衰减，根据衰减的程度即 影响肌松药作用的药效动力学 年龄 新生儿：体重剂量与成人相似 消除半衰期↑ 老年人：用量↓ 消除半衰期↑ 机制：体液↓ 肝肾血流减少，降低肌松药消除 注：不依赖肝肾消除的肌松药不受限 影响肌松药的药效动力学 神经肌肉疾病 重症肌无力患者对非去极化肌松药非常敏感，而对去极化肌松药不敏感，但后者易发生II相滞。 肌无力综合征的病人对二者都十分敏感。 家族性周期性麻痹患者根据血钾水平选择肌松药，高钾血症避免用琥珀胆碱 假性胆碱酯酶异常 主要影响琥珀酰胆碱 药物相互作用 吸入全麻药： 机理：CNS抑制 减少ACH通道的开发时间 增加非去极化肌松药作用，强→弱:异氟烷、恩氟烷、地氟烷、七氟烷、氟烷、氧化亚氮。 对氯筒箭毒碱，泮库溴铵，哌库溴铵作用比较明显，减量1／2 -1／3 对维库溴铵、阿曲库铵作用较弱。减量1／4 对去极化肌松药作用较弱 药物相互作用 局麻药和抗心律失常药理机制： 局麻药药理机制 减少ACH囊泡的排放 抑制后膜Na通道→ACH敏感性↓ 取代Ca离子 自身阻滞神经肌肉接