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Pharmacology: Pharmacodynamics: Atracurium is a competitive nondepolarising neuromuscular-blocking agent which acts by competing with acetylcholine for occupancy of receptors on the post-synaptic membrane. Thus, the receptors sites are blocked by Atracurium resulting in failure of contraction and eventual flaccid paralysis.
Pharmacokinetics: The pharmacokinetics of Atracurium in man are essentially linear with the 0.3-0.6 mg/kg dose range. The elimination half-life is approximately 20 minutes, and the volume of distribution is 0.16 L/kg. Atracurium is 82% bound to plasma proteins.
Atracurium is degraded spontaneously mainly by a non-enzymatic decomposition process (Hofmann elimination) which occurs at plasma pH and at body temperature and produces breakdown products which are inactive. Degradation also occurs by ester hydrolysis catalysed by non-specific esterases. Elimination of atracurium is not dependent on kidney or liver function.
The main breakdown products are laudanosine and a monoquaternary alcohol which have no neuromuscular blocking activity. The monoquaternary alcohol is degraded spontaneously by hofmann elimination and excreted by the kidney. Laudanosine is excreted by the kidney and metabolised by the liver. The half-life of laudanosine ranges from 3-6 hours in patients with normal kidney and liver function. It is about 15 hours in renal failure and is about 40 hours in renal and hepatic failure. Peak plasma levels of laudanosine are highest in patients without kidney or liver function and average 4 μg/ml with wide variation.
Concentration of metabolites are higher in ICU patients with abnormal renal and/or hepatic function. These metabolites do not contribute to neuromuscular block.
