新斯的明拮抗国产阿曲库铵效果及对Q-T离散度的影响

目的研究不同剂量新斯的明拮抗国产阿曲库铵肌松恢复作用的效果及对QT离散度(QTd)的影响.方法30例ASA Ⅰ～Ⅱ级患者,随机分为三组,每组10例.分别给予新斯的明20μg/kg(N20组)、30μg/kg(N30组)和40μg/kg(N40组),观察拮抗阿曲库铵肌松作用恢复时间及对QTd的影响.结果新斯的明20μg/kg产生的肌松恢复效果弱于30μg/kg和40μg/kg,而30 μg/kg和40μg/kg所产生的效果相似.新斯的明20 μg/kg、30μ/kg对QTd的影响不明显,而40μg/kg新斯的明明显增大QTd.结论新斯的明剂量由20μg/kg增加到40 μg/kg,肌松恢复加快,但增大QTd.     

Model-based adaptive closed-loop feedback control of atracurium-induced neuromuscular blockade

Closed-loop control of atracurium-induced neuromuscular blockade by a model-based adaptive feedback algorithm is described. Mean offsets (+/- s.d.) from setpoints at 50, 70 and 90% neuromuscular blocks using the Relaxograph were 1.1 +/- 1.3, 0.2 +/- 0.7 and 0.1 +/- 0.4%, respectively. Correspondingly, the mean steady-state rates of infusion of atracurium were 0.20 +/- 0.06, 0.25 +/- 0.03 and 0.39 +/- 0.10 mg.kg-1.h-1. The described controller provides reasonable control of atracurium dosing at different degrees of neuromuscular blockade. It gives a solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Neuromuscular blocking agents block carotid body neuronal nicotinic acetylcholine receptors

Neuromuscular blocking agents predominantly block muscle type nicotinic acetylcholine receptors as opposed to the neuronal type. However, there is growing evidence that neuromuscular blocking agents have affinity to some neuronal nicotinic acetylcholine receptors. The carotid body chemoreceptor as the essential oxygen-sensing cell, relies on cholinergic signalling. Atracurium and vecuronium impair carotid body chemoreceptor activity during hypoxia. Here, we characterize atracurium and vecuronium as antagonists at nicotinic receptors of the carotid body chemoreceptor. Isolated rabbit carotid body preparations with carotid sinus nerve were used, and chemoreceptor activities were recorded. There was a concentration-dependent reduction in the chemoreceptor responses to nicotine, with an IC(50) to 50 microg nicotine of 3.64 and 1.64 microM and to 500 microg nicotine of 27.00 microM and 7.29 microM for atracurium and vecuronium, respectively. It is concluded that atracurium and vecuronium depress nicotine-induced chemoreceptor responses of the carotid body in a dose-dependent fashion.     

Intradermal Histamine Release by 3 Muscle Relaxants

The induration and redness caused by intradermal injections of equipotent doses of atracurium, vecuronium and d-tubocurarine were measured in six healthy, male volunteers. Atracurium and d-tubocurarine were almost indistinguishable in their reactions. Vecuronium caused a significantly smaller response than both atracurium and d-tubocurarine. We therefore suggest that of these three drugs, vecuronium may cause the least histamine release and is, perhaps, the drug of choice in patients with a history of asthma or allergy.     

Assessment of the Presynaptic Effect of Atracurium: Train-of-Four and Tetanic Stimulation in in Vitro Preparations

The present experiments were designed to study the effect of atracurium on the contractile responses produced by repetitive motor nerve stimulation and by depolarizing drugs in frog, chick and rat skeletal muscle-nerve preparations, using electrophysiological and neurochemical techniques. The presynaptic effect of atracurium was assessed using train-of-four (2 Hz) and tetanic stimulation (50 Hz) in isolated chick and rat neuromuscular junctions. A further measure of the presynaptic effect of atracurium was examined by studying its effect on the uptake of labelled choline, 3H-methylcholine, in the control preparations. The effect of atracurium on postjunctional contractile responses of the chick isolated biventer cervicis skeletal muscle was studied using cholinergic drugs such as acetylcholine and tetraethylammonium. The results indicated that in addition to its postjunctional competitive and non-depolarizing blocking effect, atracurium may have a prejunctional inhibitory action at the neuromuscular junction. Atracurium reduced all the contractile responses produced by both electrical and chemical stimulation.     

爱肌松的药效学及其对循环功能的影响

对６６例心脏病手术和非心脏病手术患者，比较爱肌松和阿曲可林的药效学及其对循环功能的影响．结果表明：（１）在心脏手术中，两药起效时间相近；（２）近５０％的爱肌松组病例需用新斯的明拮抗；（３）两药对循环功能无明显影响。因此，爱肌松适用于心脏和非心脏病手术患者的麻醉诱导和维持。     

The Effects of d-Tubocurarine, Pancuronium and Atracurium on the Responses of Gastrocnemius and Soleus Muscles in the Cat

In vivo, the effects of d-tubocurarine (0.20 mg kg-1), pancuronium (0.015 mg kg-1) and atracurium (0.15 mg kg-1) on the responses of the indirectly stimulated cat gastrocnemius (fast) and soleus (slow) muscles to a twitch, train-of-four and tetanic stimuli were studied. The soleus muscle demonstrated a greater degree of fade than the gastrocnemius in response to tetanic stimuli (50 Hz). There was no difference between the responses of the two muscles to twitch or train-of-four stimuli with any of the drugs. Recovery of train-of-four ratio occurred more rapidly than did the tetanic fade ratio. At a time when train-of-four ratio exceeded 0.7, tetanic fade was still evident, especially in the soleus muscle.     

Tetanic fade during neuromuscular blockade produced by atracurium in the rat diaphragm preparation

In the present investigation, we studied and measured the phenomenon of tetanic fade and peak tetanic tension depression in the rat diaphragm preparation in the presence of a blocking concentration of atracurium (e.g., 10 μmol.l^-1). Atracurium (10 μmol.l^-1) produced a pronounced tetanic fade (i.e., 47–69% reduction of total sustained tetanic tension) at a time (15 s) when it reduced the peak tetanic tension by only 25%. The time course for total tetanic fade was 30–35 s, whereas the time taken for complete peak tetanic tension depression was 3-3.5 min, suggesting that the two effects were produced via different mechanisms, involving presynaptic and postsynaptic mechanism. It was concluded that atracurium produces a profound tetanic fade, with respect to its effect on twitch or tetanic tension, suggesting that the drug is a potent neuromuscular blocker, with rapid onset of blockade.     

Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants

The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium, and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which Hofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of speculation, and this, coupled with the fact that atracurium is a mixture of 10 isomers, has led to the development of many innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis -isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent volume of distribution and an elimination half-time similar to that of pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two isomers of mivacurium are very similar, whereas the third isomer differs greatly in both pharmacological activity and elimination half-time, so that analysis requires complex pharmacokinetic methods.