Suxamethonium Metoclopramide

METOCLOPRAMIDE SUXAMETHONIUM Possible t efficacy of suxamethonium Uncertain Be aware and monitor effects of suxamethonium closely... 

Metoclopramide is structurally related to orthoclopramide, a procaine derivative, and it can prolong the action of suxamethonium because of competition for cholinesterase. However, its common side effects are similar to those seen with phenothiazine derivatives. In high doses, a range of extrapyramidal symptoms may develop. The anti-emetic effects of metoclopramide are due to two main actions. Centrally, it blocks dopamine in the CTZ and peripherally, it hastens gastric emptying, abolishes irregular intestinal contractions, and increases... 

Metoclopramide inhibits the activity of plasma cholinesterase and can prolong the action of suxamethonium (SEDA-14, 115) (320-322). 

Kao YJ, Tellez J, Turner DR. Dose-dependent effect of metoclopramide on cholinesterases and suxamethonium metabolism. Br J Anaesth 1990 65(2) 220-4. 

Not understood. Studies with human plasma failed to find any evidence that cimetidine in therapeutic concentrations inhibits the metabolism of suxamethonium. However, metoclopramide may do and therefore is possibly the drug responsible for any interaction seen. In vitro studies with very high cimetidine concentrations found inhibition of plasma cholinesterase (pseudocholinesterase) activity. The cimetidine/vecuro-nium interaction is not understood, but it has been suggested that cimetidine may reduce the hepatic metabolism of vecuronium. ... 

Information seems to be limited to the reports cited. The most likely explanation for the discord between the cimetidine/suxamethonium results is that in the one study reporting increased suxamethonium effects some of the patients were also given metoclopramide, which can inhibit plasma cholinesterase and prolong the effects of suxamethonium (see also Neuromuscular blockers + Metoclopramide , p.l27). In four other studies, cimetidine and other H2-receptor antagonists did not alter suxamethonium effects. Therefore, it seems unlikely that an interaction exists. There is some evidence that cimetidine may slightly prolong the effects of vecuronium, but ranitidine appears not to interact. Atracurium and rocuro-nium appear not to be affected. Overall these possible interactions seem to be of little clinical significance. 

Turner DR, Kao YJ, BivonaC. Neuromuscular block by suxamethonium following treatment with histamine type 2 antagonists or metoclopramide. BrJ Anaesth (1989) 63, 348-50. 

The neuromuscular blocking effects of suxamethonium (succinylcholine) and mivacurium can be increased and prolonged in patients taking metoclopramide. 

Metoclopramide is postulated to reduce the activity of plasma cholinesterase, which is responsible for the metabolism of suxamethonium and mivacurium. One in vitro study found that a metoclopramide level of 800 nanograms/mL inhibited plasma cholinesterase aetivity by 50%. However, a 10-mg dose of metoclopramide in adult patients weighing 50 to 70 kg produces peak plasma levels five times less than this (140 nanograms/mL). Further, in an in vivo study, metoclopramide had only minimal inhibitory effects on plasma cholinesterase, and there was no difference in plasma cholinesterase levels in patients who had received metoclopramide and those who had not. ... 

The interaction between metoclopramide and suxamethonium is an established but not extensively documented interaction of only moderate or minor clinical importance. However anaesthetists should be aware that some enhancement of blockade can occur. The interaction between metoelopra-mide and mivacurium has only more recently been demonstrated. Metoclopramide appears to allow a reduction in the infusion rate of mivaeurium and it causes a significant delay in recovery from neuromuscular block. Care is recommended during combined use. The authors of the suxamethonium reports also point out that plasma cholinesterase activity is reduced in pregnancy and so suxamethonium sensitivity is more likely in obstetric patients. Ester-type local anaesthetics also depend on plasma... 

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