Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adverse reactions seen following administration of neuromuscular blocking agents are mainly cardiovascular. Due to the lack of specificity for the nicotinic receptor at the neuromuscular junction, these agents may interact with receptors in autonomic ganglia and muscarinic receptors in the heart. Furthermore, muscle relaxants may have histamine-releasing properties. The cardiovascular effects vary with potency and specificity of the drug, depending mainly on the chemical structure. Pancuronium, fazadinium and especially gallamonium block cardiac muscarinic receptors, and tachycardia may be seen. Atracurium, metocurine and in particular d-tubocurarine have histamine-releasing properties and may cause flushing, hypotension and tachycardia. Vecuronium has no effect on the cardiovascular system. The effect of succinylcholine on heart rate differs between children, where bradycardia is seen, and adults in whom tachycardia may follow. However, bradycardia may occur in adults following a single dose. Succinylcholine increases plasma potassium, especially in patients with nerve damage, and arrhythmias may be observed. The neuromuscular adverse effects of succinylcholine, such as fasciculations and increased gastric and intraocular pressure, may be prevented by precurarisation. Many drugs interact with neuromuscular blocking agents and there is often a potentiation of the neuromuscular effect. This is of clinical importance in the case of antibiotics, inhalational anaesthetics, lithium and cyclosporin. Difficulty in reversing the block may occur with calcium channel blockers and polymyxin. However, some drugs, such as phenytoin, carbamazepine and lithium, may cause resistance to neuromuscular blocking agents. Furthermore, clinically important interactions exist between individual neuromuscular blocking drugs. Precurarisation with a non-depolarising drug prolongs the onset of succinylcholine, and conversely a prolonged effect of non-depolarising drugs is seen following succinylcholine. The effect of succinylcholine is markedly prolonged if the drug is administered during recovery from pancuronium blockade or following neostigmine for reversal. Succinylcholine is hydrolysed by plasma cholinesterase, and drugs which decrease the activity of this enzyme may produce a prolonged block, i.e. contraceptive pills, cyclophosphamide, echothiopate and organophosphate.
 ...
PMID:Adverse reactions and interactions of the neuromuscular blocking drugs. 268 31

Succinylcholine 2-5 mg or atracurium 10-15 mg were given on five separate occasions to a 24-year-old, 64 kg woman homozygous for atypical plasma cholinesterase who was undergoing electroconvulsive therapy (ECT). Atracurium blockade was reversed with atropine, 0.6 mg and edrophonium, 35 mg. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis muscle was recorded. Doses producing 90 per cent first twitch blockade were 2.5 and 15 mg for succinylcholine and atracurium respectively. The onset of action was 6 min for both relaxants, and time to 90 per cent first twitch recovery was 20 min for succinylcholine and 16 min for the atracurium-edrophonium combination. It is concluded that the use of atracurium in these patients does not offer marked advantages over small doses of succinylcholine.
 ...
PMID:Comparison of atracurium and succinylcholine for electroconvulsive therapy in a patient with atypical plasma cholinesterase. 358 97

The use of atracurium during anaesthesia for abdominal hysterectomy in a 37-year-old patient with homozygous plasma cholinesterase [EsEs] deficiency is described. Intubation was achieved utilizing 0.47 mg X kg-1 of atracurium. Subsequent doses of 0.08 mg X kg-1, 0.12 mg X kg-1 and 0.12 mg X kg-1 were given 34, 57 and 78 minutes respectively after the initial dose. At the time of reversal of the residual effects of neuromuscular blockade, 26 minutes after the last dose, spontaneous respiration had resumed. The duration of action of the drug was not different from that described in normal patients. Atracurium would appear to be a safe drug to provide neuromuscular relaxation in patients with plasma cholinesterase deficiency, where surgical procedures of intermediate duration are being undertaken.
 ...
PMID:Use of atracurium in a patient with plasma cholinesterase deficiency. 382 87

Atracurium, a new non-depolarizing neuromuscular blocking agent, was studied in 70 patients anesthetized with fentanyl, thiopental, and nitrous oxide-oxygen. The dose found to produce 95% twitch inhibition (ED95) was 0.2 mg/kg. The onset time from injection to maximum depression of twitch was 4.0 minutes at this dose; the duration to 95% recovery was 44.1 minutes. Twice the ED95 dose (0.4 mg/kg) had an onset time of 1.7 minutes and a duration of 63.5 minutes. No cardiovascular effects were observed in this dosage range. At higher doses (0.5 and 0.6 mg/kg) arterial pressure decreased 13% and 20% and heart rate increased 5% and 8%, respectively. Sixteen patients received at least four successive doses of atracurium. No clinically significant cumulative effect could be shown when recovery from 25% to 75% of control twitch height was compared for initial and final doses in the series. Atracurium spontaneously decomposes at physiologic pH via the Hofmann elimination reaction and may also undergo ester hydrolysis independent of plasma cholinesterase. These proposed pathways of inactivation may explain the lack of cumulative effect and the drug's intermediate duration of action. Based on the results of this study, atracurium offers several clinical advantages and should undergo more extensive clinical trials.
 ...
PMID:Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. 621 81

Atracurium, a new competitive neuromuscular blocking agent, is broken down in the body by two mechanisms, Hofmann elimination and ester hydrolysis. Chemical breakdown by Hofmann elimination is rapid at physiological pH and temperature, whereas ester hydrolysis is enzyme-catalysed but by enzymes other than pseudocholinesterase. The products of these reactions have been shown to lack neuromuscular or cardiovascular activity at the concentrations occurring after therapeutic doses of atracurium. Studies with radiolabelled drug in anaesthetized cats have shown that atracurium and its metabolites are readily excreted in bile and urine. Plasma kinetics are unaltered if renal function is negated by bilateral ligation of all renal blood vessels. Preliminary studies have indicated that atracurium does not cross the placenta to a significant extent and that the drug can be used safety in Caesarean section.
 ...
PMID:Metabolism and kinetics of atracurium: an overview. 668 12

Atracurium is a potent competitive neuromuscular blocking agent in anesthetized man with no cardiovascular effects at doses required for paralysis. Endotracheal intubation can be accomplished after i.v. doses of 0.6 and 0.3 mg kg-1, within 1 and 2 min respectively. Paralysis is readily antagonized by neostigmine and is enhanced by halothane. The consistent response in terms of block and recovery which emerged when the drug was given as increments of 0.05 or 0.1 mg kg-1 indicates the absence of cumulative effects. The course of action of atracurium was appreciably shorter than that of other recognized competitive blocking agents. Doses of 0.3--0.6 mg kg-1 i.v. provided adequate relaxation during surgical intervention for 15--45 min; spontaneous recovery without the use of neostigmine was observed in some patients. In addition to the non-enzymic decomposition by "Hofmann Elimination", atracurium may also undergo an enzymic ester hydrolysis but, unlike suxamethonium, it may not be destroyed by pseudocholinesterase.
 ...
PMID:Evaluation of atracurium in anaesthetized man. 745 85

Mivacurium is a short-acting nondepolarising muscle relaxant of the benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With 2.5 fold ED95, tracheal intubation can be accomplished within 2-3 min following injection. The ensuing DUR 25% (i.e. time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine and about half as long as with equipotent doses of atracurium and vecuronium. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to a moderate histamine release following doses of 3-4 times the ED95. In patients with end stage liver or renal disease as well as in patients with atypical plasma cholinesterase the duration of action of mivacurium is prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking agent chemically related to vecuronium. Compared with the latter, rocuronium is less potent, has a shorter onset of action, and no cumulative effects. Adequate intubating conditions are achieved within 60 to 90 s after i.v. injection of twice the ED95. Its elimination from the blood occurs primarily via liver uptake, while renal elimination is about 10 to 30%. Slight vagolytic effects are reported following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis-atracurium, is five times as potent as the chiral mixture while having a similar pharmacodynamic and kinetic profile. It does not cause significant histamine release or clinically relevant cardiovascular effects at doses up to 8 times the ED95. Laudanosine release seems to be less with cis-atracurium than with atracurium.
 ...
PMID:[New muscle relaxants]. 886 25

Present administration of electroconvulsive therapy (ECT) is safe for most patients. Succinylcholine is used and tolerated as one of several pharmacologic agents in the routine protocol. Relatively rare medical conditions, including pseudocholinesterase deficiency, cholinesterase inhibition, and severe neuromuscular disease, may complicate the use of succinylcholine. This article presents three cases in which the standard protocol was altered, using atracurium in place of succinylcholine to provide brief and well-controlled muscle relaxation. Atracurium is an alternative medication for ECT in those cases in which succinylcholine use is problematic.
 ...
PMID:ECT Modified by Atracurium. 1194 Aug 91