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Steroids Dec 2021Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively...
Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the H, C, and N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
Topics: Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Neuromuscular Blocking Agents; Vecuronium Bromide
PubMed: 34655596
DOI: 10.1016/j.steroids.2021.108928 -
Journal of Anesthesia Apr 2016Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common... (Review)
Review
Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.
Topics: Anaphylaxis; Androstanols; Anesthesia; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine; Sugammadex; Vecuronium Bromide; gamma-Cyclodextrins
PubMed: 26646837
DOI: 10.1007/s00540-015-2105-x -
British Journal of Pharmacology Jan 2006Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular... (Review)
Review
Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built-in self-destruct mechanism that makes them specially useful in kidney or liver failure, and the vecuronium group, which are specially free from unwanted side effects. Of this latter group, the compound rocuronium is of special interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors.
Topics: Animals; Atracurium; History, 16th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Muscle, Skeletal; Nerve Block; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Nicotinic Antagonists; Receptors, Nicotinic; Synaptic Transmission; Tubocurarine; Vecuronium Bromide
PubMed: 16402115
DOI: 10.1038/sj.bjp.0706404 -
British Journal of Anaesthesia Nov 1985The interaction between two non-depolarizing neuromuscular blocking agents, pancuronium bromide and vecuronium bromide, has been studied at standardized levels of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The interaction between two non-depolarizing neuromuscular blocking agents, pancuronium bromide and vecuronium bromide, has been studied at standardized levels of neuromuscular blockade and alternating the sequence of their administration, in 40 surgical patients. The drug administered first appeared invariably to play a dominant role in influencing both the dose requirements and the duration of action of the subsequent neuromuscular blocker. This resulted in reduced dose requirements and significant prolongation of action of vecuronium administered after pancuronium and increased dose requirements and shortening of neuromuscular blocking action of pancuronium given during vecuronium-induced partial neuromuscular blockade. Possible mechanisms of such interaction are discussed.
Topics: Adult; Drug Interactions; Female; Humans; Male; Muscle Contraction; Neuromuscular Blocking Agents; Pancuronium; Time Factors; Vecuronium Bromide
PubMed: 2864945
DOI: 10.1093/bja/57.11.1063 -
European Review For Medical and... Apr 2017To observe the influences of atracurium besylate and vecuronium bromide on muscle relaxant effects and electromyography of patients with tracheal intubation under... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To observe the influences of atracurium besylate and vecuronium bromide on muscle relaxant effects and electromyography of patients with tracheal intubation under general anesthesia in thyroid surgery.
PATIENTS AND METHODS
120 patients treated with thyroid surgery were randomly divided into group A and group V. Patients in group A were administered with cisatracurium besylate combined with propofol and fentanyl for induction of tracheal intubation under general anesthesia. Patients in group V were administered with 0.10 mg/kg vecuronium bromide combined with propofol and fentanyl for induction of tracheal intubation under general anesthesia. Then, the amplitude in electromyography was observed 30-70 min after I.V. muscle relaxant medicine to record the time for patients to reach 0% TW convulsion in abductor pollicis muscle and to observe the muscle relaxant effects.
RESULTS
There was no statistical difference in the time to reach 0% TW in two groups (p>0.05). After 30 min of injection of muscle relaxants, EMG positive rate and TW value in group A were significantly higher than those in group V (p<0.05). After 50-70 min of injection of muscle relaxants, EMG positive rate of patients in two groups was up to 100%, and EMG amplitude in group A was significantly higher than that in group V (p<0.05). The time of taking muscle relaxant effects in group A was significantly faster than that in group V (p<0.05), while the recovery time of autonomous respiration and the time of autonomous body activity in group A were slightly lower than those in group V (p>0.05). There was no statistical difference in the time of eye-opening of both groups (p>0.05). MAP and HR of patients in both groups showed no statistical difference before and after injection (p>0.05).
CONCLUSIONS
Average EMG amplitude and the positive rate of effective EMG amplitude of cisatracurium besylate are all higher than those of vecuronium bromide. With faster effects and shorter action time, cisatracurium besylate is more suitable in thyroid surgery IONM (intraoperative neurophysiological monitoring).
Topics: Adult; Anesthesia, General; Atracurium; Electromyography; Female; Humans; Intubation, Intratracheal; Male; Middle Aged; Neuromuscular Blocking Agents; Vecuronium Bromide
PubMed: 28485777
DOI: No ID Found -
Anesthesiology May 2001
Topics: Bronchial Spasm; Humans; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide
PubMed: 11388519
DOI: 10.1097/00000542-200105000-00006 -
Anesthesiology Jul 1987To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the...
To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70-84 yr) and 12 young adults (30-57 yr) during halothane-nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 +/- 1.0 and 5.2 +/- 0.8 ml X kg-1 X min-1, respectively), and volume of distribution at steady-state (179 +/- 31 and 244 +/- 38 ml X kg-1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium.
Topics: Adult; Aged; Aged, 80 and over; Aging; Half-Life; Humans; Middle Aged; Muscles; Neuromuscular Junction; Osmolar Concentration; Pancuronium; Vecuronium Bromide
PubMed: 2886080
DOI: 10.1097/00000542-198707000-00008 -
Anesthesiology Oct 1988Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and... (Comparative Study)
Comparative Study
Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed.
Topics: Animals; Bile; In Vitro Techniques; Liver; Male; Pancuronium; Perfusion; Rats; Rats, Inbred Strains; Vecuronium Bromide
PubMed: 2902816
DOI: 10.1097/00000542-198810000-00007 -
Anaesthesia Apr 1993
Topics: Androstanols; Drug Interactions; Hemodynamics; Humans; Neuromuscular Nondepolarizing Agents; Rocuronium; Scopolamine; Vecuronium Bromide
PubMed: 8098589
DOI: 10.1111/j.1365-2044.1993.tb06973.x -
British Journal of Anaesthesia Oct 1983
Topics: Atracurium; Humans; Isoquinolines; Neuromuscular Blocking Agents; Pancuronium; Vecuronium Bromide
PubMed: 6138052
DOI: 10.1093/bja/55.10.1042