Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mercury Pharmaceuticals Limited, Capital House, 85 King William Street, London EC4N 7BL, UK
Pharmacotherapeutic group: Peripherally acting muscle relaxants, choline derivatives,
ATC code: M03AB01
Short-acting depolarising neuromuscular blocking agent.
Suxamethonium, an analogue of acetylcholine, inhibits neuromuscular transmission by depolarising the motor end plates in skeletal muscle. The depolarisation may be observed as fasciculation. Subsequent neuromuscular transmission is inhibited as long as an adequate concentration of suxamethonium remains at the receptor site. Onset of flaccid paralysis occurs within 30-60 seconds of intravenous injection and with single administration persists for 2-6 minutes.
The paralysis following administration of suxamethonium is progressive, with differing sensitivities of different muscles. This initially involves consecutively the levator muscles of the face, muscles of the glottis and finally the intercostals and the diaphragm and all other skeletal muscles.
The short duration of suxamethonium is considered to be due to its rapid metabolism in the blood. Suxamethonium is rapidly hydrolysed by plasma cholinesterase to succinylcholine (which possesses clinically insignificant depolarising muscle relaxant properties) and then more slowly to succinic acid and choline.
Following intravenous administration, there is rapid hydrolysis by pseudocholinesterase with the initial metabolite being succinylmonocholine a weak neuro-muscular drug. The pharmacokinetics of a bolus dose of suxamethonium have been studied in anaesthetised adult patients using a high performance liquid chromatographic assay.
The pharmacokinetic parameters for suxamethonium 1mg/kg and 2mg/kg respectively are: apparent volume of distribution 16.4 ± 14.7ml/kg and 5.6 ± 6.8ml/kg; area under the plasma concentration-time curve 124.3 ± 163.2 and 695 ± 1008.9 minutes/microgram/ml.
The arterial blood suxamethonium concentration at 30 and 120 seconds following injection of suxamethonium 1mg/kg are 79.5 ± 108.4 and 3.3 ± 6.7 micrograms/ml, and following injection of 2mg/kg suxamethonium are 336.2 ± 512.5 and 7.2 ± 13.0 micrograms/ml, respectively.
Only a small fraction of suxamethonium reaches the neuromuscular junction. Its action is terminated by diffusion away from the end plate.
Succinylcholine does not readily cross the placenta.
Succinylmonocholine is metabolised to succinic acid with only a small amount excreted in the urine. The pharmacokinetic parameters for suxamethonium 1mg/kg and 2mg/kg respectively are: total body clearance 40.5 ± 38.7 and 15.0 ± 14.8 litre/min and elimination half-life 16.6 ± 4.8 and 11.7 ± 4.5 seconds.
No bacterial mutation assays have been conducted.
There are some data to suggest a weak clastogenic effect in mice, but not in patients who had received suxamethonium chloride.
Carcinogenicity studies have not been performed.
Animal reproduction studies have not been conducted with suxamethonium. It is also not known whether suxamethonium can affect reproductive capacity or cause foetal harm when administered to a pregnant woman.
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