Chemical formula: C₆₅H₈₂N₂O₁₈S₂ Molecular mass: 1,242.5 g/mol PubChem compound: 47320
Atracurium besilate is a non-depolarising neuromuscular blocking agent with an intermediate duration of action, administered intravenously to produce skeletal muscle relaxation.
Non-depolarising neuromuscular blocking agents antagonise the action of the neurotransmitter acetylcholine by competitively binding with cholinergic receptor sites on the motor endplate of the myoneural junction. These effects may be inhibited or reversed by the administration of anticholinesterases such as neostigmine or pyridostigmine.
As with other non-depolarising neuromuscular blocking agents, the time to onset or paralysis is reduced, and the duration of maximum effect prolonged, with increasing atracurium doses.
Once recovery from atracurium’s neuromuscular blocking effect begins, it proceeds more rapidly than recovery from tubocurarine, alcuronium, and pancuronium. Regardless of the atracurium dose, the time from start of recovery (from complete block) to complete recovery (as measured by restoration of the tetanic response to 95% of normal) is approximately 30 minutes under balanced anaesthesia, and approximately 40 minutes under halothane, enflurane or isoflurane anaesthesia. Repeated doses have no cumulative effect on recovery rate.
With initial atracurium besilate doses up to 0.5 mg/kg, plasma histamine levels were shown to increase by 15% in a dose dependant way, but haemodynamic changes were minor within this dose range. Following the administration of 0.6 mg/kg of atracurium besilate, histamine levels were shown to increase by 92%, and were shown to correlate with a transient (5 minutes) decrease in blood pressure and a brief (2 to 3 minutes) episode of skin flushing. While these effects are of little clinical significance in most patients, the possibility of substantial histamine release at recommended doses must be considered in sensitive individuals, or in patients in whom substantial histamine release would be especially hazardous (e.g. patients with significant respiratory or cardiovascular disease).
Studies in malignant hyperthermia-susceptible pigs indicated that atracurium besilate does not trigger this syndrome. Clinical studies in patients with a history of malignant hyperthermia revealed the same results.
Atracurium besilate does not appear to affect intraocular pressure, therefore, it is a suitable agent for ophthalmic surgery.
The limited data in neonates from literature reports suggest variability in the time to onset and duration of action of atracurium in this population as compared to children.
The pharmacokinetics of atracurium besilate in humans are essentially linear within the dose range of 0.3 to 0.6 mg/kg. The elimination half-life is approximately 20 minutes. The protein binding of atracurium is approximately 82%. The volume of distribution of atracurium is 0.16 l/kg and plasma clearance of atracurium is about 6.5 ml/min/kg. Some placental transfer occurs in humans. The umbilical venous to maternal venous drug concentration ratios are between 0.03 and 0.33 (mean 0.12+/-0.04).
The duration of neuromuscular blockade produced by atracurium does not correlate with plasma pseudocholinesterase levels and is not altered by the absence of renal function. This is consistent with the results of in vitro studies which have shown that atracurium is inactivated in plasma via two non-oxidative pathways: ester hydrolysis, catalysed by non-specific esterases; and Hofmann elimination, a non-enzymatic chemical process which occurs at physiological pH and body temperature. The rate of Hofmann elimination, which is the principal route of elimination for atracurium, is increased at a higher pH or at higher temperatures, and reduced at a lower pH or lower temperatures.
Limited clinical experience on long term administration of atracurium besilate show only minimal effects of haemofiltration or haemodialysis on plasma levels of atracurium and its metabolites. The effects of haemoperfusion on plasma levels of atracurium and its metabolites are not known.
Carcinogenicity studies have not been performed. Atracurium yielded negative results for gene mutation in bacteria, and chromosomal damage in bone marrow of rats. A positive response in the mouse lymphoma assay was observed only at highly cytotoxic concentrations. This single positive response is not considered to be of clinical relevance.
Animal studies have indicated that atracurium has no adverse effect on foetal development.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
