The first NMJ blocker to be discovered was curare, a poison used on the tips of arrows or spears by hunters to paralyze their game. Animals died when their respiratory muscles became paralyzed. Because the poison was destroyed by the cooking process or by gastric acid if the meat were eaten raw, it was safe for humans. Curare was first purified for clinical use as the NMJ blocker tubocurarine, which has since been replaced with more refined drugs that can control onset and duration of effect.
发现的首种NMJ阻滞药是箭毒，这是狩猎者涂在弓箭或长矛头部的一种毒素，用以麻痹猎物。动物呼吸肌麻痹时就会死亡。因为烹饪会破坏这种毒素，生吃时动物时则会遭到胃酸破坏，所以，它对人类来说是安全的。箭毒首次提纯用于临床是作为NMJ阻滞药筒箭毒碱使用的，此后便被起效和作用时间可控的更纯净药物替代。
Nondepolarizing NMJ blockers include atracurium (generic), cisatracurium (Nimbex), pancuronium (generic), rocuronium (generic), and vecuronium (generic).
非去极化NMJ阻滞药包括阿曲库铵（通用名）、顺式阿曲库铵（赛机宁）、泮库溴铵（通用名）、罗库溴铵（通用名）和维库溴铵（通用名）。
Nondepolarizing NMJ blockers are used when clinical situations require or desire muscle paralysis. Therapeutically, nondepolarizing NMJ blockers:
临床情形需要或想要肌肉麻痹时可使用非去极化NMJ阻滞药。从治疗角度看，非去极化NMJ阻滞药：
Serve as an adjunct to general anesthetics during surgery when reflex muscle movement could interfere with the surgical procedure or the delivery of gas anesthesia.
在反射肌肉运动可能影响手术操作或输送气体麻醉时作为手术期间全麻的辅助药物
Facilitate mechanical intubation by preventing resistance to passing of the endotracheal tube and in situations in which patients “fight” or resist the respirator.
预防气管内管通过阻力及在患者“对抗”或抵抗呼吸器时使用，方便机械通气进行
Facilitate various endoscopic diagnostic procedures when reflex muscle reaction could interfere with the procedure.
在反射肌反应可能影响操作时，为多种内镜诊断操作提供便利
Facilitate electroconvulsive therapy when intense skeletal muscle contractions as a result of electric shock could cause the patient broken bones or other injury.
电休克所致骨骼肌强烈收缩可能引起患者骨折或其他损伤时使用，方便电惊厥疗法
All nondepolarizing NMJ blockers are similar in structure to ACh and compete with ACh for the muscle ACh receptor site. As a result, they occupy the muscular cholinergic receptor site and do not allow stimulation to occur. These agents do not cause the activation of muscle cells, and consequently muscle contraction does not occur. Because they are not broken down by acetylcholinesterase, their effect is longer lasting than that of ACh. The nondepolarizing NMJ blockers are hydrophilic instead of lipophilic, so they do not readily cross the blood–brain barrier and have little effect on the ACh receptors in the brain.
Nondepolarizing NMJs are metabolized in the serum, although metabolism is dependent on the liver to produce the needed plasma cholinesterases. Most of the metabolites are excreted in the urine.
非去极化NMJs在血清中代谢，尽管代谢有赖肝脏生产必需的血浆胆碱酯酶。多数代谢产物随尿排出。
Each nondepolarizing NMJ blocker differs in terms of time of onset and duration. The drug of choice in any given situation is determined by the procedure being performed, including the estimated time involved.
每种非去极化NMJ阻滞药的起效时间和持续时间都不相同。任何已知情形的首选药物由所行损伤，--包括相关预估时间，由正在施行的操作而定。
★Vocabulary★
curare – n. 箭毒
poison – n. 毒素，毒药
paralyze – v. 使麻痹
game – n. 比赛，猎物
purify – v. 提纯，净化
tubocurarine – n. 筒箭毒碱
refine – v. 精炼，精制
atracurium – n. 阿曲库铵
cisatracurium – n. 顺式阿曲库铵 Nimbex – n. 赛机宁(阿曲库铵商品名)
pancuronium – n. 泮库溴铵
rocuronium – n. 罗库溴铵
vecuronium – n. 维库溴铵
adjunct – n. 附属物，辅助疗法
endotracheal – a. 气管内折
electroconvulsive therapy – 电惊厥疗法
intense – a. 强烈的，浓郁的
hydrophilic – a. 亲水的
lipophilic – a. 亲脂的
metabolite – n. 代谢产物
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★Video ★
Nondepolarizing NMJ Blockers
★Test ★
1. Curare kills animals because it paralyzes the animal’s respiratory muscles. However, it is safe for humans because of the following. Select all that apply.
A. The poison is only fatal to the game
B. The poison can be destroyed by the cooking process
C. The poison can be destroyed by gastric acid
D. The poison is not fatal to humans 2. All the items below are correct EXCEPT. Select all that apply.
A. Nondepolarizing NMJ blockers are similar in structure to ACh.
B. Nondepolarizing NMJ blockers are all the same in time of onset and duration
C. Nondepolarizing NMJ blockers are not lipophilic
D. Nondepolarizing NMJ blockers are used as general anesthetics during surgery.
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答案 Answers
1. B, C.
Rationale: Curare is safe for humans because the poison is destroyed by the cooking process or by gastric acid if the meat is eaten raw. Otherwise, it is also fatal to humans.
2. B, D.
Rationale: Nondepolarizing NMJ blockers differ in terms of time of onset and duration. They are used as an adjunct to general anesthetics.
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