非去极化肌松药发生残余阻滞作用的危险因素

目的 介绍非去极化肌松药发生残余阻滞作用的危险因素。方法 通过归纳总结近年来国内外相关文献，分别从年龄、性别、选用的药物及药物相互作用等因素与非去极化肌松药肌松效应的关系来阐述肌松药发生残余阻滞作用的危险因素。结果 年龄、性别、药物、并存疾病等均可影响非去极化肌松药的肌松效应。结论 掌握相关因素、合理掌握肌松药的用量、做好肌松监测工作，对预防术后肌松残余及呼吸系统不良并发症的发生有重要的意义。     

新型肌肉松弛药-罗库溴铵研究进展

了解神经肌肉兴奋传递这一生理过程对于理解肌肉松弛药的药理和肌松药的拮抗是必需的和非常有帮助的.骨骼肌的随意运动和肌张力的维持都有赖于神经、肌肉结构和功能以及神经-肌肉兴奋传递的正常.肌松药主要作用于接头后膜的受体,与乙酰胆碱竞争受体.按其作用机制不同,分为去极化肌松药和非去极化肌松药.去极化肌松药有与乙酰胆碱相似的结构,与受体结合后有类似乙酰胆碱的作用,使终板持续去极化,阻滞了正常的神经肌肉兴奋传递.非去极化肌松药与受体结合后阻滞了乙酰胆碱与受体结合,从而防止了去极化发生.     

潘库溴铵预处理对琥珀胆碱临床效应的影响

临床上常用亚肌松量的非去极化肌松剂预处理预防去极化肌松剂琥珀胆碱引起的肌颤、术后肌痛等不良反应.已发现小剂量非去极化肌松药预处理后,去极化肌松药的起效减慢,阻滞程度低,几松恢复时间缩短.但不同的非去极化     

肿瘤患者使用去极化肌松药发生Ⅱ相阻滞临床观察

为探讨肿瘤患者在全身麻醉手术中使用去极化肌松药发生Ⅱ相阻滞的发生情况及用抗胆碱酯酶药拮抗对肌松的影响，总结以下资料，报告如下。     

右美托咪定对老年人膝关节置换术顺苯磺酸阿曲库铵肌松效应的影响观察

<正>顺苯磺酸阿曲库铵为阿曲库铵的单一结构体,是一种中时效非去极化肌松药[1]。药理学研究证实该种药物的肌松强度约为阿曲库铵的4倍,具有心血管反应小、无明显蓄积作用的应用优势,是现阶段我国临床中应用较为广泛的一种肌松药[2]。近年来,国内外临床研究均发现有多种因素可对顺苯磺酸阿曲库铵的肌松效应产生影响,包括患者机体内环境、温度、麻醉等,且多数临床研究所得结果     

阿曲库铵粉针剂肌松效应的临床观察

肌松药是全麻的重要辅助药 ,主要分为去极化和非去极化两大类。阿曲库铵和维库溴铵等新药应用于临床以来 ,临床肌松药的应用模式有很大影响。其中阿曲库铵属苄异喹啉类 ,因其独特的Hofmann降解方式可在生理体温和PH条件下代谢消除 ,而具有对肝肾功能无影响、无蓄积作用等优点 ,因而在临床上得以广泛应用。但进口阿曲库铵水剂要求在低温下运输、保存 ,否则影响药物效价、使用不便。部分地区并因此而一度中断对其使用。国产粉针剂阿曲库铵解决了这一困难 ,本文旨在观察国产粉针剂阿曲库铵的肌松效应及对心血管的影响 ,并观察临床用量有无不…     

顺式阿曲库铵肌松作用的临床观察

顺式阿曲库铵是中时效非去极化肌松药,是阿曲库铵的10种同分异构体之一,为顺式旋光异构体,具有与阿曲库铵类似的肌松效应及代谢方式。     

氨茶碱对腹腔镜手术七氟醚麻醉下罗库溴铵残余肌松的影响

<正>腹腔镜手术在主要步骤完成之前需要维持深度肌松以利于术野显露和手术操作。术后残余肌松的相关风险大,但并未引起足够重视。残余肌松是导致术后呼吸系统并发症的主要危险因素之一,可引起低氧血症、高碳酸血症、吸入性肺炎、肺不张、急性肺水肿等,甚至致残或有生命危险~([1])。常规拮抗残余肌松作用在临床麻醉领域已达成广泛共识,有效拮抗可减少相关并发症,提高麻醉安全性,但有关拮抗模式和药     

术前长期使用苯妥英钠对维库溴铵效果影响的临床观察

手术前用药,特别是长期使用某类药物,可以影响麻醉及手术中使用的药物的效果,产生增强或降低其作用的效应,从而影响麻醉深度的调节。本文报道了术前长期使用抗癫痫药苯妥英钠对非去极化肌肉松弛剂维库溴铵（仙林）肌松效果的影响。     

术前长期使用苯妥英钠对维库溴铵效果影响的临床观察

手术前用药,特别是长期使用某类药物,可以影响麻醉及手术中使用的药物的效果,产生增强或降低其作用的效应,从而影响麻醉深度的调节.本文报道了术前长期使用抗癫痫药苯妥英钠对非去极化肌肉松弛剂维库溴铵(仙林)肌松效果的影响.     

Part 4: Use of relaxants in paediatric and elderly patients, in obstetrics, and in the intensive care unit

The pharmacodynamic and pharmacokinetic characteristics of the non-depolarizing muscle relaxants are dependent on age. Thus differences are found between paediatric patients, adults, and elderly patients. Muscle relaxants cross the placenta and thus may cause problems in the fetus. Many of the potential adverse effects of relaxant administration are seen more pronounced in intensive care patients. Prolonged effects and problems in weaning patients from the ventilator are observed when muscle relaxants are used in such patients. Critical illness neuropathy is a syndrome different from relaxant induced neuromyopathy, but may be enhanced by relaxant administration.     

Part 2: Pharmacology of neuromuscular blocking agents

Clinically, neuromuscular blockade is induced with either depolarizing or nondepolarizing relaxants. Suxamethonium is the only depolarizing relaxant still in use. It is hydrolysed in the plasma by pseudocholinesterase (plasma cholinesterase). In some patients and in particular diseases the plasma cholinesterase activity is low and hence the effect of suxamethonium prolonged. Suxamethonium is characterized by sideeffects such as myalgia, fasciculations and increase in intraocular, intracranial and intragastric pressure. More serious adverse reactions are masseter muscle spasm and potassium release, in patients with some neuromuscular diseases and increase in extrajunctional acetylcholine receptors. As nondepolarizing muscle relaxants benzylisoquinolines and steroidal compounds are mainly used. Each relaxant has its own pharmacological characteristics. The effect of most relaxants depends on liver and renal function because the pharmacokinetic behaviour is strongly dependent on these organs. Also, acidbase balance disturbances, change in temperature, and neurological diseases have an effect on the profile of the relaxants. A number of drugs (anaesthetics, antibiotics, antiepileptics, etc.) have an effect on neuromuscular transmission, and thus interact with the relaxants. Some non-depolarizing relaxants cause histamine release and cardiovascular effects.     

神经肌肉阻滞药及其拮抗药的临床应用及市场现状

神经肌肉阻滞药是一种作用于外周神经系统、不具有中枢作用的肌肉松弛药,常作为手术麻醉时的辅助用药,但它的使用会导致阻滞残留作用,临床上常用拮抗药拮抗或者逆转其残留阻滞作用。本文总结了近年来神经肌肉阻滞药及其拮抗药的临床应用及市场现状,并阐述了其在国内的发展机遇和挑战。     

Org-NC45: a new steroidal non-depolarizing muscle relaxant

Although pancuronium has fewest side effects compared to other currently used non-depolarizing muscle relaxants, it is still not the ideal relaxant. Its structural analogues have been studied to derive such an ideal relaxant. Org-Nc45 meets the requirements for such a relaxant best and is therefore extensively studied. It is more potent than pancuronium, has a shorter onset and duration of action and is free from cardiovascular side effects. Histamine release could not be demonstrated. It can be easily reversed by neostigmine, pyridostigmine or 4-aminopyridine. Interaction with antibiotics and anaesthetic drugs is not different from that of pancuronium.     

Org-NC45: a new steroidal non-depolarizing muscle relaxant

Although pancuronium has fewest side effects compared to other currently used non-depolarizing muscle relaxants, it is still not the ideal relaxant. Its structural analogues have been studied to derive such an ideal relaxant. Org-Nc45 meets the requirements for such a relaxant best and is therefore extensively studied. It is more potent than pancuronium, has a shorter onset and duration of action and is free from cardiovascular side effects. Histamine release could not be demonstrated. It can be easily reversed by neostigmine, pyridostigmine or 4-aminopyridine. Interaction with antibiotics and anaesthetic drugs is not different from that of pancuronium.     

Simulation of Interaction Between Two Non-depolarizing Muscle Relaxants: Generation of an Additive or a Supra-additive Neuromuscular Block

GOAL: To examine in a model of neuromuscular transmission the interaction between two non-depolarizing muscle relaxants. An additive or a supra-additive interaction was evaluated as a function of the affinities of acetylcholine and the muscle relaxants for the two binding sites at a single receptor. METHODS: Affinity of acetylcholine for site1 was postulated to be higher than for site2. Muscle relaxants may display a similar pattern of affinities, a higher affinity for site2, or the affinities may be identical. Receptors with both sites occupied by acetylcholine are activated and, if their concentration at an end plate surpasses the critical threshold, initiate contraction of the associated muscle fiber. The number of contracting muscle fibers determines twitch strength of the whole muscle. Neuromuscular block (NMB) = 1--twitch. NMB was simulated for muscle relaxants acting as single agents or in three types of combinations. (a) Complementary fractions of equieffective concentrations. (b) Variable combinations of equieffective concentrations producing NMB equal to NMB produced by the single muscle relaxant (isobolographic analysis), and (c) NMB-vs.-concentration relationship of single agents and of their combination in a fixed ratio. RESULTS: Additive interaction was simulated for pairs of muscle relaxants displaying identical ratios of affinities. All other pairs produce a supra-additive interaction, more prominent, the more divergent the patterns of affinities. The slopes of NMB-vs.-concentration curves were steeper for supra-additive combinations than for single agents. CONCLUSION: The simulations define conditions leading to additive or supra-additive interaction and suggest an experimental design suitable to test the results.     

Pharmacokinetics of steroidal muscle relaxants in isolated perfused rat liver.

Both in humans and animals hepatic elimination is an important factor determining the duration of action of non-depolarizing neuromuscular blocking drugs. To elucidate the hepato-biliary disposition of muscle relaxants the pharmacokinetics of several structurally related but physicochemically distinct steroidal neuromuscular blocking drugs were studied in isolated perfused rat livers. Pharmacokinetics analysis with the DIFFIT computer program enabled the simultaneous fitting of independently measured perfusate disappearance and biliary excretion rate curves using a numerical approach. The hepatic disposition of the steroidal muscle relaxants could be adequately described by a three compartment model with elimination from the peripheral compartment V2 (biliary excretion) and storage in a deep compartment (V3) connected to V2. In addition, for vecuronium only slow ester hydrolysis occurring in V2 and V3 was included in the model. The lipophilicity rather than the relative mobility of the muscle relaxants showed a positive relationship with biliary clearance (Cl20) and the initial hepatic uptake (Cl12), indicating that hepato-biliary transport of these organic cations is highly dependent on the hydrophobic character of the compounds. In addition, net hepatic uptake of the steroidal cations was influenced markedly by transport from the liver to perfusate (hepatic efflux). This hepatic efflux (k21) decreased with increasing lipophilicity. In contrast, the extent of intracellular sequestration into deep compartments, indicated by high k23/k32 ratios, seemed to be inversely related to the lipophilicity of the muscle relaxants and might explain the observed prolonged hepatic storage of some of these compounds. In combination with data from subfractionation studies the results indicate that the pharmacokinetic analysis of the hepatic disposition of steroidal muscle relaxants may be used to evaluate actual transport phenomena participating in the hepatic disposition of these drugs.     

Recent advances in neuromuscular blocking agents

Since the introduction of (+)-tubocurarine into anaesthetic and surgical practice (1942), a number of non-depolarizing neuromuscular blocking agents (NMBs) with improved pharmacological properties have been developed during the last sixty years. However, after withdrawal of rapacuronium from clinical use, there is still a need for an ultra-short acting non-depolarizing muscle relaxant with rapid onset as substitution for the polarizing suxamethonium, which has several undesirable side-effects. In this paper, structure-activity relationships within four different series of NMBs (tetrahydroisoquinolinium, bistropinyl diester, aminosteroid, and amino peptide analogues) published in this millennium have been reviewed. The NMB properties of the most promising drug candidates from each series were discussed and compared to those of the already existing muscle relaxants.     

Newer Neuromuscular Blocking Agents

Four neuromuscular blocking drugs, doxacurium, mivacurium, pipecuronium, and rocuronium have been or are about to be introduced into clinical practice. The purpose of this MiniReview is to describe their pharmacology, to consider their place in clinical anaesthetic practice, and to examine whether the needs of the clinican have been met. Two of the agents (doxacurium, mivacurium) are benzylisoquinolines resembling atracurium and two (pipecuronium, rocuronium) are aminosteroids related to pancuronium and vecuronium. Two (doxacurium, pipecuronium) are long-acting compounds, similar in duration of action to pancuronium, although the need for such a profile is questionable. Rocuronium has an intermediate duration of action and produces its maximum effect within two minutes which is much more rapid than any other non-depolarizing relaxant and this is probably a result of its poor potency. However, the onset of paralysis is not as quick as after succinylcholine. Mivacurium is unique because it is metabolized by plasma cholineslerase which produces a rapid recovery although slower than succinylcholine. All of the new drugs are devoid of serious cardiovascular or other side effects. The anaesthetist is now presented with an armamentarium of safe, non-depolarizing muscle relaxants with varying durations of action. However, the rapid onset and recovery associated with succinylcholine are unique and important in the urgent control of a patient's airway and respiration. The indications for succinylcholine will not disappear and the search for a non-polarizing replacement will continue.     

Suramin reverses non-depolarizing neuromuscular blockade in rat diaphragm.

Unexpectedly, it was observed that the P2-purinoceptor antagonist, suramin (10 microM to 1 mM), reversed the muscle paralysis caused by structurally unrelated non-depolarizing relaxants. Suramin competitively reversed the blocking action of pancuronium. Both the pre- and postsynaptic blockade of nicotinic receptors by pancuronium was counteracted, as shown by the action of suramin, using train-of-four stimulation. Suramin did not affect the paralysis caused by the depolarizing relaxant, succinylcholine. The reversal action of suramin was not due to an increase in the acetylcholine concentration in the synaptic cleft, since neither the contraction of preparations partially paralysed by diminished acetylcholine release in the presence of low Ca2+ or high Mg2+ nor acetylcholinesterase activity were affected. Suramin did not affect the reduction in twitch tension caused by adenosine and potentiated the ATP-induced reduction in twitch, indicating that ATP-sensitive receptors are not involved in the reversal action of suramin. Consequently, these results suggest that the action of suramin is due to binding with a site on the acetylcholine receptor also occupied by non-depolarizing relaxants, but different from the site occupied by succinylcholine.