Cisatracurium Atracurium

C20H25NO4 73074-37-2) see Atracurium besilate (/t)-tetrabydropapaverine 7V-acetyl-L-leucinate (C2gH4(,N207 141109-12-8) see Cisatracurium besylate ( )-tetrabydropapaverine bydrocbloride (C20H26CINO4 6429-04-5) see Cisatracurium besylate [ -( , 5 )]-2,3,4,9-tetrabydro-7V-(l-phenylethyt)-lff-carbazol-3-amine sulfate (1 1)... 

Cisatracurium or atracurium in the presence of renal and/or hepatic dysfunction... 

Up to 30-min time to recovery with an intermediate-acting neuromuscular blocker (i.e., atracurium, cisatracurium, rocuronium, and vecuronium)... 

Agent Tubocuranine Pancuronium Vecuronium Atracurium Rocuronium Cisatracurium Mivacurium Cis-trans isomer Trans-trans isomer C/s-c/s isomer... 

The duration of clinical relaxation with cisatracurium is slightly longer than following equipotent doses of atracurium and ranges from about 35-65 minutes with doses of... 

The major metabolic pathway for cisatracurium is Hofmann elimination, although renal and other organ clearance accounts for some elimination. The pharmacokinetics of cisatracurium are independent of dose in healthy adult patients up to doses of 0.2 mg-kg-1 and its elimination half-life is similar to that of atracurium (Table 6.4). In contrast to atracurium, the clearance of cisatracurium is slightly reduced and recoveiy slightly slower in patients with renal failure. Much less laudanosine is produced as a metabolite of cisatracurium as compared with atracurium even when the drug is given by continuous infusion over a prolonged period of time. 

Atracurium has several stereoisomers, and the potent isomer cisatracurium has become one of the most commonly used muscle relaxants in clinical practice. Although cisatracurium resembles atracurium, it has less dependence on hepatic inactivation, produces less laudanosine, and is less likely to release histamine. From the clinical perspective, cisatracurium has all the advantages of atracurium with fewer side effects. Therefore, cisatracurium has largely replaced atracurium in clinical practice. 

Cisatracurium Similar to tubocurarine Like tubocurarine but lacks histamine release and antimuscarinic effects Prolonged relaxation of surgical procedures relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit Not dependent on renal or hepatic function duration, 25-45 min Toxicities Prolonged apnea but less toxic than atracurium... 

By competition with acetylcholine (atracurium, cisatracurium, mivacurium, pancuronium, rocuro-nium, vecuronium). These drugs are competitive antagonists of acetylcholine. They do not cause depolarisation themselves but protect the endplate from depolarisation by acetylcholine. The result is a flaccid paralysis. 

Cisatracurium is a stereoisomer of atracurium it is less prone to cause histamine release. 

Cisatracurium is one of the ten isomers of atracurium. With an ED95 of 0.05 mg/kg it is about three times more potent than atracurium (1-3). The duration of action of cisatracurium tends to be slightly longer than that of atracurium. Less cisatracurium is required to achieve a given degree of neuromuscular blockade and so less lau-danosine is produced. 

Cisatracurium and atracurium share the same metabolic pathways, but Hofmann elimination may have a greater role in the elimination of cisatracurium than in atracurium (2,4-7). Spontaneous in vivo degradation accounts for 77 % of total body clearance of cisatracurium (6). Organ clearance is 23% of total body clearance. Major metabolites of cisatracurium are laudanosine and a monoquaternary acrylate. 

Welch RM, Brown A, Ravitch J, Dahl R. The in vitro degradation of cisatracurium, the R, cis-R -isomer of atracurium, in human and rat plasma. Clin Pharmacol Ther 1995 58(2) 132-42. 

Schramm WM, Papousek A, Michalek-Sauberer A, Czech T, lUievich U. The cerebral and cardiovascular effects of cisatracurium and atracurium in neurosurgical patients. Anesth Analg 1998 86(l) 123-7. 

Clinically important, potentially hazardous interactions with aminophylline, atracurium, cisatracurium, doxacurium, epinephrine, ergometrine, mivacurium, non-depolarizing muscle relaxants, oxprenolol, oxytocin, pancuronium, rapacuronium, rifampin, vecuronium, xanthines... 

NMBAs are further differentiated by their duration of action during anesthesia. Succinylcholine and mivacurium are common ultra-short-acting competitive NMBAs (5-10 min). An intermediate duration of action (30-45 min) is maintained with the use of atracurium, cisatracurium, rocuronium and vecuronium. A long-lasting duration of action (90-100 min) is observed with d-tubocurarine, doxacurium, metocurine, pancuronium and pipecuronium. 

Spontaneous or plasma ChE, intermediate-short duration Atracurium Cisatracurium Mivacurium... 

C. Known hypersensitivity or anaphylactic reaction (non-dose-related) to agent or presenrative (eg, benzyl alcohol). Succinylcholine is most commonly implicated, but anaphylaxis has been reported with rocuronium, atracurium, mi-vacurium, and cisatracurium. 

A reduced recovery time from atracurium-induced neuromuscular blockade was found in one study in patients taking long-term antiepileptics including phenytoin but other studies have reported a minimal effect, see (e) below. For a report of reduced recovery time, increased clearance of cisatracurium and increased resistance to its actions in the presence of phenytoin, see (a) above. 

Kim KS, Chun YS, Choi SU, Suh IK. Neuromuscular intemction between cisatracurium and mivacurium, atracurium, vecurcnium or rocuronium administered in combination. Anaesthesia (1998) 53, 872-8. 

Laudanosine or Af-methyltetrahydropapaverine is a recognized metabolite of atracurium and cisatracurium. Laudanosine decreases the seizure threshold, and thus, it can induce seizures if present at sufficient threshold concentrations however, such concentrations are unlikely to be produced consequent to chemodegradable metabolism of clinically admiiustered doses of cisatracurium or atracurium. Laudanosine also occurs naturally in minute amounts (0.1 %) in opium, from which it was first isolated in 1871. Partial dehydrogenation of laudanosine will lead to papaverine, the alkaloid found in the opium poppy plant (Papaver somniferum). Laudanosine is a benzyltetrahydroisoquinoline alkaloid. It has been shown to interact with GABA receptors, opioid receptors, and ificotinic acetylcholine receptors, but not benzodiazepinergic or muscarinic receptors which are also involved in epilepsy and other types of seizures. 

Nondepolarizing muscle relaxants are highly dependent on renal elimination if not inactivated otherwise. Degradation pathways of the relaxants atracurium or cisatracurium bypass renal function, making them preferable in renal insufficiency. Rocuronium has an increased elimination half-life in renal failure, but its action is swiftly and reliably terminated by i.v. administration of sugamma-dex. 

To counter the problems produced by laudanosine, the stereoisomers of atracurium were isolated in order to allow a dose reduction. Cisatracurium (Fig. 16.24) is an... 

R-cis R-cis isomer of atracurium. It is degraded by Hofmann elimination just like atracurium. However, plasma concentrations of laudanosine do not reach such high levels as in the case of atracurium, leading to fewer cardiac side effects. Cisatracurium also releases less histamine from tissue stores. The potency and duration of action are similar in both drugs. Cisatracurium besilate is provided in sterile injections with a concentration equivalent to 2 mg/mL of cisatracurium in 5- or 10-mL vials, or 10 mg/mL of cisatracurium in 20-mL vials intended for use in ICUs only. 

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