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11 Muscle relaxants and anticholinesterasesaltered potency. Elimination is independent of metabolism with 70% excreted in
the urine and 30% in bile as unchanged drug. It accumulates in patients with renal
failure in whom a greater proportion is excreted in the bile.Atracurium
Atracurium is a benzylisoquinolinium compound that is formulated as a mixture of
10 stereoisomers, resulting from the presence of 4 chiral centres.Presentation and uses
Atracurium is presented as a colourless solution containing 10 mg.ml−^1 in 2.5, 5 and
25 ml vials and should be stored at 4◦C. At 0.5 mg.kg−^1 intubating conditions are
reached within 90–120 seconds.Other effects
Cardiorespiratory – following rapid administration it may precipitate the release
of histamine, which may be localized to the site of injection but may be gener-
alized resulting in bronchospasm and hypotension. Slow intravenous injection
minimizes these effects.
Myopathy – in a manner similar to that of vecuronium, atracurium is associated
with critical illness myopathy.Kinetics
Atracurium has a unique metabolic pathway, undergoing ester hydrolysis and Hof-
mann elimination.
Ester hydrolysis – non-specific esterases unrelated to plasma cholinesterase are
responsible for hydrolysis and account for 60% of atracurium’s metabolism. The
breakdown products are a quaternary alcohol, a quaternary acid and laudanosine.
Unlike Hofmann elimination, acidic conditions accelerate this metabolic pathway.
However, pH changes in the clinical range probably do not alter the rate of ester
hydrolysis of atracurium.
Hofmann elimination – while atracurium is stable at pH 4 and at 4◦C, Hofmann
elimination describes its spontaneous breakdown to laudanosine and a quaternary
monoacrylate when placed at normal body temperature and pH. Acidosis and
hypothermia will slow the process. Both breakdown products have been shown to
have potentially serious side effects (i.e. seizures), but at concentrations in excess
of those encountered clinically. Laudanosine, while being a glycine antagonist, has
no neuromuscular-blocking properties and is cleared by the kidneys.
These metabolic pathways result in a drug whose elimination is independent of
hepatic or renal function, which in certain clinical situations is advantageous.Cis-atracurium
Cis-atracurium is one of the ten stereoisomers present in atracurium.