Suxamethonium

As GA: NOT an anaesthetic, but is used as adjunct in general anaesthesia. Neuromuscular blocking drug causes muscle relaxation, blocking reflex movements that would otherwise occur during noxious procedures. Suxamethonium binds to nAChRs at muscle end plate where it acts as an agonist to cause depolarization. It is not hydrolyzed to by AChE and so causes prolonged depolarization of the end plate, leading to conformational changes in the receptor that allow sodium channel closure.

As neuromuscular blocking agent: Suxamethonium results in sustained neuromuscular depolarization preventing further transmission. This leads to short-lasting (normally) muscle relaxation (muscle paralysis) which is of clinical benefit during initiation of a general anaesthetic or during electroconvulsive therapy (ECT). Suxamethonium is the only depolarizing blocker that is still used clinically.

As GA: A very prolonged paralysis occurs in about 1:2000 individuals, who have genetic deficiency of plasma psuudocholinesterase - the enzyme that metabolizes the drug (i.e. NOT the enzyme acetylcholinesterase which is sited at end plate). See pharmacogenetics.

As neuromuscular blocking agent: Bradycardia - direct muscarinic action of ACh. Potassium release - motor endplates have increased cation permeability, hence potassium loss from muscle and increased plasma concentrations which may cause arrhythmias. Increased intraocular pressure - extraocular muscles contract, causing pressure on the eyeball. Prolonged paralysis - in individuals with low plasma cholinesterase levels (1:2000 individuals, who have genetic deficiency of plasma psuudocholinesterase - the enzyme that metabolizes the drug - not the enzyme acetylcholinesterase which is sited at end plate) or in those receiving anti-cholinesterase drugs. Activation then block of nAChR can lead to muscle damage or painful sensation from muscles on recovery.

As GA: With high and repeated doses, suxamethonium produces a complex "dual block". This is caused by the development of a non-depolarising block following the initial depolarising block.

As neuromuscular blocking agent: The main difference is in the reversal of these two types of neuromuscular-blocking drugs. Note the difference between the non-depolarizing (e.g. atracurium) and depolarizing blockers or neuromuscular transmission. The former are reversed by anticholinesterase inhibitor drugs because they are competitive antagonists at the nAChR receptor so can be reversed by increases in ACh. The depolarizing blockers already have ACh-like actions, so these agents will have prolonged effect under the influence of anticholinesterase inhibitors. Depolarizing blockers will initially exhibit fasciculations (a sudden twitch just before paralysis occurs) due to the depolarization of the muscle and there is often post-operative muscle pain. These are not features of the non-depolarising blockers. OTHER MUSCLE RELAXANTS. Dantrolene sodium is a muscle relaxant that is currently the only specific and effective treatment for malignant hyperthermia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis) and ecstasy intoxication.