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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 Medical Journal Apr 1947
Topics: Curare; Humans; Tubocurarine
PubMed: 20248062
DOI: 10.1136/bmj.1.4503.579 -
Tidsskrift For Den Norske Laegeforening... Feb 2010Muscle relaxants were introduced into clinical anaesthesia for the first time in 1942. The purpose of this article is to provide an overview of the history of muscle... (Review)
Review
BACKGROUND
Muscle relaxants were introduced into clinical anaesthesia for the first time in 1942. The purpose of this article is to provide an overview of the history of muscle relaxants, their mode of action and their role in current anaesthetic practice.
MATERIAL AND METHOD
The review is based on clinical experience, own research and a non-systematic literature search using PubMed.
RESULTS
A muscle relaxant is either suxamethonium (curacit) or one of many curare compounds. One of the curare drugs was brought to Europe from South America in the 1700 s and the active substance (called d-tubocurarine) was isolated in 1935. This type of drug paralyses striated muscles that are under voluntary control by interfering with the normal signalling system between nerve and muscle. Muscle relaxants provide optimal relaxation of skeletal muscles during surgical procedures, an effect that otherwise may require the use of high doses of anaesthetic drugs. However, muscle relaxants are not anaesthetic drugs, do not affect consciousness and have no pain relieving effect. A muscle relaxant that works optimally in all clinical settings has unfortunately not been developed so far.
INTERPRETATION
Muscle relaxants are generally safe drugs when used appropriately, but especially suxamethonium may have serious side effects. A muscle relaxant is regularly used during induction of anaesthesia, but less during surgery, because modern anaesthetics possess some muscle relaxing effect.
Topics: History, 20th Century; Humans; Motor Endplate; Neuromuscular Nondepolarizing Agents; Preanesthetic Medication; Receptors, Cholinergic; Succinylcholine; Tubocurarine
PubMed: 20220868
DOI: 10.4045/tidsskr.08.0323 -
Anaesthesia Nov 1985
Topics: Adult; Bradycardia; Female; Humans; Intraoperative Complications; Tubocurarine
PubMed: 4073439
DOI: 10.1111/j.1365-2044.1985.tb10635.x -
Proceedings of the Royal Society of... Aug 1948
Topics: Tubocurarine
PubMed: 18877134
DOI: No ID Found -
British Journal of Anaesthesia Sep 1980
Topics: Anesthesiology; Humans; Infant, Newborn; Neuromuscular Junction; Pancuronium; Succinylcholine; Synaptic Transmission; Tubocurarine
PubMed: 6254549
DOI: 10.1093/bja/52.9.962-a -
British Journal of Anaesthesia Jul 1976Tubocurarine, given as a single bolus, may be used safely for neuromuscular blockade in the neonate. The recommended dose is 250 mug/kg at birth, increasing to 500...
Tubocurarine, given as a single bolus, may be used safely for neuromuscular blockade in the neonate. The recommended dose is 250 mug/kg at birth, increasing to 500 mug/kg at 28 days of age. This dose should be reduced in the event of prematurity, acidosis or hypothermia, or when certain antibiotics or inhalation anaesthetic agents are present in the tissues. A single dose as described has a duration of approximately 1 h and it is only after this time that satisfactory antagonism can be obtained. The potency of pancuronium when compared with tubocurarine in the study is 6:1, from birth to 28 days.
Topics: Age Factors; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Pancuronium; Tubocurarine
PubMed: 1016646
DOI: 10.1093/bja/48.7.687 -
Anaesthesia Sep 1993Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine.
Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Double-Blind Method; Female; Gastric Acid; Humans; Hydrogen-Ion Concentration; Hypotension; Middle Aged; Morphine; Premedication; Ranitidine; Terfenadine; Tubocurarine
PubMed: 8214491
DOI: 10.1111/j.1365-2044.1993.tb07584.x -
Anesthesiology Apr 1976In ten patients anesthetized with halothane and nitrous oxide, d-tubocurarine or pancuronium was infused continuously for 80 minutes to produce a constant 90 per cent...
In ten patients anesthetized with halothane and nitrous oxide, d-tubocurarine or pancuronium was infused continuously for 80 minutes to produce a constant 90 per cent depression of twitch tension. For the first 30-minutes period, 8.2 +/- 0.32 and 1.09 +/- 0.06 (mean +/- SE) mg/m2 of d-tubocurarine or pancuronium, respectively, were required, and for the last 30-minutes period (50 to 80 minutes of infusion) 2.1 +/- 10.10 and 0.41 +/- 0.02 mg/m2 were required, giving potency ratios of 8.2/1.1, i.e., 7.4, and 2.1/0.41, i.e., 5.1. The difference in potency ratios in the first and last 30-minutes periods implies that potency values determined by single-injection techniques inadequately describe the relative requirements for sustained paralysis. The mean ratios between that amount of relaxant representing tissue uptake and that amount representing metabolism and renal excretion during the first 30 minutes were 3.06 +/- 0.28 for d-tubocurarine and 1.63 +/- 0.19 for pancuronium. The significantly higher ratio for d-tubocurarine implies that its tissue uptake relative to metabolism and renal excretion is greater than that for pancuronium. The higher ratio for d-tubocurarine may be partly explained by its greater binding to plasma and tissue proteins.
Topics: Adult; Humans; Middle Aged; Protein Binding; Tubocurarine
PubMed: 1259187
DOI: 10.1097/00000542-197604000-00005 -
British Journal of Anaesthesia Feb 1972
Topics: Acute Kidney Injury; Adjuvants, Anesthesia; Humans; Kidney Failure, Chronic; Kinetics; Models, Biological; Time Factors; Tubocurarine
PubMed: 5016882
DOI: 10.1093/bja/44.2.163