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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 -
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 -
British Medical Journal Apr 1947
Topics: Curare; Humans; Tubocurarine
PubMed: 20248062
DOI: 10.1136/bmj.1.4503.579 -
Anaesthesia Nov 1985
Topics: Adult; Bradycardia; Female; Humans; Intraoperative Complications; Tubocurarine
PubMed: 4073439
DOI: 10.1111/j.1365-2044.1985.tb10635.x -
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 Sep 1982The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n...
The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.
Topics: Adolescent; Adult; Aging; Anesthesia, General; Child; Child, Preschool; Electromyography; Half-Life; Halothane; Humans; Infant; Infant, Newborn; Kinetics; Models, Biological; Nitrous Oxide; Tubocurarine
PubMed: 7114542
DOI: 10.1097/00000542-198209000-00009 -
Anesthesiology Jan 1979The potencies of metocurine and d-tubocurarine for neuromuscular and autonomic blockade and histamine release were determined in cats anesthetized with chloralose and...
The potencies of metocurine and d-tubocurarine for neuromuscular and autonomic blockade and histamine release were determined in cats anesthetized with chloralose and pentobarbital. The autonomic margins of safety of these drugs were determined by measuring the ratios of ED50 for sympathetic block to ED95 for neuromuscular block; ED50 for vagal block to ED95 for neuromuscular block; ED50 for histamine release to ED95 for neuromuscular block. Metocurine is 14 times more potent than d-tubocurarine as a neuromuscular blocking agent in the cat, but its autonomic blocking action is three times weaker than the of d-tubocurarine and its histamine-releasing action is less than half that of d-tubocurarine. The combination of higher neuromuscular blocking potency and weaker autonomic effect gives metocurine a much higher autonomic margin of safety than d-tubocurarine in the cat.
Topics: Animals; Autonomic Nerve Block; Autonomic Nervous System; Cats; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Histamine Release; Male; Neuromuscular Junction; Synaptic Transmission; Tubocurarine
PubMed: 83803
DOI: 10.1097/00000542-197901000-00009 -
Anaesthesia 1979Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside.
Topics: Adolescent; Adult; Aged; Arthroplasty; Drug Interactions; Ferricyanides; Humans; Hypotension, Controlled; Middle Aged; Neuromuscular Junction; Nitroprusside; Pancuronium; Prospective Studies; Synaptic Transmission; Time Factors; Tubocurarine
PubMed: 231914
DOI: 10.1111/j.1365-2044.1979.tb06248.x -
Anesthesiology Aug 1983This study was designed to compare the effects of three neuromuscular blocking agents, in a clinically relevant dose range, on the regional distribution of blood flow... (Comparative Study)
Comparative Study
This study was designed to compare the effects of three neuromuscular blocking agents, in a clinically relevant dose range, on the regional distribution of blood flow measured with 15-microns radioactive microspheres in anesthetized, optimally ventilated cats. d-Tubocurarine (400, 800, and 1,600 micrograms X kg-1) caused hypotension and a decrease in ascending aortic blood flow. Pancuronium (20, 40, and 80 micrograms X kg-1) only caused a moderate tachycardia, while vecuronium (40, 80, and 160 micrograms X kg-1) was devoid of any systemic hemodynamic effect. Neither pancuronium nor vecuronium caused major changes in regional blood flows. On the other hand, d-tubocurarine increased blood flow to the stomach but decreased that to the kidneys, liver, skin, spleen, intestine, and adrenal glands. These effects of d-tubocurarine show a striking resemblance to those elicited by the infusion of histamine. Blood flow to the nerve-stimulated tibialis anterior muscle, which was about six times that of the unstimulated muscle, was decreased significantly by all three neuromuscular blockers. In conclusion, the results clearly show that, while d-tubocurarine produces major cardiovascular disturbances, pancuronium and, in particular, vecuronium do not cause serious changes in systemic and regional hemodynamics in doses that are two to four times the ED90 for neuromuscular blocking action.
Topics: Animals; Blood Gas Analysis; Cats; Female; Hemodynamics; Male; Muscles; Neuromuscular Nondepolarizing Agents; Pancuronium; Regional Blood Flow; Tubocurarine; Vascular Resistance; Vecuronium Bromide
PubMed: 6135374
DOI: 10.1097/00000542-198308000-00006