Cisatracurium

Overdose with cisatracurium may result in neuromuscular blockade beyond the time needed for surgery and anesthesia. The primary treatment is maintaining sedation, a patent airway, and controlled ventilation until recovery of neuromuscular function is assured. There should be no attempt at reversal if there is evidence or suspicion of complete neuromuscular blockade.

M03AC11

M - Musculo-skeletal system

The dose required to produce 95% suppression of twitch response to nerve stimulation (ED₉₅) of cisatracurium is 0.05 mg/kg in adults receiving opioid/nitrous oxide/oxygen anesthesia. The degree and duration of the neuromuscular block produced by cisatracurium increases in a dose-dependent manner, while the time to maximum neuromuscular block decreases. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action. Cisatracurium acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine. The use of cisatracurium may lead to residual paralysis, as well as a higher risk of seizure. Medication errors increase the risk of death, and the use of certain drugs may potentiate the neuromuscular blocking action of cisatracurium.

Like other non-depolarising neuromuscular blocking agents, cisatracurium binds competitively to cholinergic receptors in motor end-plate neurons, blocking acetylcholine from accessing the receptors. Therefore, in the presence of cisatracurium, an end-plate potential cannot be developed. Ion channels remain closed, the cell does not depolarize, and an action potential is not transmitted.

The degradation of cisatracurium is largely independent of liver metabolism. Cisatracurium undergoes Hofmann elimination (a pH and temperature-dependent chemical process) to form laudanosine and the monoquaternary acrylate metabolite. Non-specific plasma esterases hydrolyze the monoquaternary acrylate metabolite to form the monoquaternary alcohol metabolite (MQA). The MQA can also undergo Hofmann elimination, but the rate of this process is slower than the one detected for cisatracurium. Laudanosine is further metabolized to desmethyl metabolites that are conjugated with glucuronic acid and excreted in the urine. Laudanosine may cause transient hypotension and, in higher doses, cerebral excitatory effects when administered to several animal species; however, the effects of laudanosine in humans have not been established.

QX62KLI41N

CISATRACURIUM

Physiologic Effects [PE] - Neuromuscular Nondepolarizing Blockade

Established Pharmacologic Class [EPC] - Nondepolarizing Neuromuscular Blocker

Cisatracurium is a Nondepolarizing Neuromuscular Blocker. The physiologic effect of cisatracurium is by means of Neuromuscular Nondepolarizing Blockade.

Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc.

The pharmacokinetics of cisatracurium follow a two-compartment open model. Cisatracurium is metabolized into laudanosine and monoquaternary alcohol metabolite (MQA). Following the IV infusion of cisatracurium, the Cmax of laudanosine and MQA were 6% and 11% of the parent compound, respectively. Compared to young patients, the volume of distribution of cisatracurium is slightly larger in elderly patients, which also leads to longer half-life values. The plasma clearance of cisatracurium was not affected by age. Patients with hepatic impairment have a slightly higher volume of distribution and plasma clearance values; however, these minor pharmacokinetic differences are not considered clinically significant. Additionally, the pharmacokinetic parameters of cisatracurium in patients with end-stage renal disease were similar to those detected in healthy adult patients.

The predominant elimination mechanism of cisatracurium is Hofmann elimination, a chemical process dependent on pH and temperature (approximately 80% in healthy surgical patients). The liver and kidney play a minor role in the elimination of cisatracurium (about 20%); however, they have a significant role in the metabolism of cisatracurium metabolites. In healthy male patients (n=6) given ¹⁴C-cisatracurium, 4% of the recovered dose was found in feces, and 95% was found in urine, mostly as conjugated metabolites. Less than 10% of the cisatracurium dose was excreted as the unchanged patent drug. In another group of patients with Foley catheters for surgical management given non-radiolabeled cisatracurium (n=12), 15% of the cisatracurium dose was excreted unchanged in urine.

Cisatracurium has a volume of distribution at steady state of 145 mL/kg. The volume of distribution of cisatracurium besylate is small due to its relatively large molecular weight and high polarity.

Cisatracurium has a plasma clearance of 4.57 mL/min/kg.