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|Systematic (IUPAC) name|
|Metabolism||By pseudocholinesterase, to succinylmonocholine and choline|
|Mol. mass||290.399 g/mol|
|(what is this?)|
Suxamethonium chloride (INN), also known as suxamethonium or succinylcholine, is a nicotinic acetylcholine receptor agonist, used to induce muscle relaxation and short-term paralysis, usually to facilitate tracheal intubation. Suxamethonium is sold under the trade names Anectine and Quelicin. It is sometimes used in combination with analgesics and sedatives for euthanasia and immobilization of horses. It is colloquially referred to as "sux" in hospital settings.
Suxamethonium acts as a depolarizing neuromuscular blocker. It acts on nicotinic receptors resulting in persistent depolarization of the motor end plate. It is degraded by butyrylcholinesterase, a plasma cholinesterase. This hydrolysis by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care, usually for facilitation of endotracheal intubation. Despite its adverse effects, including life-threatening malignant hyperthermia, hyperkalaemia, and anaphylaxis, it is perennially popular in emergency medicine because it has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the patient cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before hypoxaemia occurs.
Suxamethonium is quickly degraded by plasma butyrylcholinesterase and the duration of effect is usually in the range of a few minutes. When plasma levels of butyrylcholinesterase are greatly diminished or an atypical form is present (an otherwise harmless inherited disorder), paralysis may last much longer, as is this the case in liver failure or in neonates.
Side effects include malignant hyperthermia, muscle pains, acute rhabdomyolysis with hyperkalemia, transient ocular hypertension, constipation and changes in cardiac rhythm, including bradycardia, and cardiac arrest. In patients with neuromuscular disease or burns, a single injection of suxamethonium can lead to massive release of potassium from skeletal muscles, potentially resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced hyperkalaemia are burns, closed head injury, acidosis, Guillain–Barré syndrome, cerebral stroke, drowning, severe intra-abdominal sepsis, massive trauma, myopathy, and tetanus.
Suxamethonium does not produce unconsciousness or anesthesia, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. Therefore, administration of the drug to a conscious patient is contraindicated.
The side effect of hyperkalaemia may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per litre. The increase is transient in otherwise healthy patients. The normal range of potassium is 3.5 to 5 mEq per litre. Hyperkalaemia does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per litre. Therefore, the increase in serum potassium level is usually not catastrophic in otherwise healthy patients.
Malignant hyperthermia from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism. This overwhelms the body's capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.
Susceptibility to malignant hyperthermia (MH) is often inherited as an autosomal dominant disorder, for which there are at least six genetic loci of interest, the most prominent being the ryanodine receptor gene (RYR1). MH susceptibility is phenotype and genetically related to central core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is usually unmasked by anesthesia, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with dantrolene sodium is usually initiated; dantrolene and the avoidance of suxamethonium administration in susceptible people have markedly reduced the mortality from this condition.
The normal short duration of Suxamethonium is due to the rapid metabolism of the drug by non-specific plasma cholinesterases. However plasma cholinesterase activity is reduced in some people due to either genetic variation or acquired conditions, this results in a prolonged duration of neuromuscular block. Genetically ninety six percent of the population have a normal (Eu:Eu) genotype and block duration, however some people have abnormal genes (Ea, Es, Ef) which can be found in varying combinations with the Eu gene or other abnormal genes. All will result in a longer duration of block from 20 minutes up to several hours. Acquired factors that effect plasma cholinesterase activity include pregnancy, liver disease, renal failure, cardiac failure, thyrotoxicosis, cancer and a number of other drugs.
If unrecognised by a clinician it could lead to awareness if anaesthesia is discontinued whilst still paralysed or hypoxaemia (and potentially fatal consequences) if artificial ventilation is not maintained. Normal treatment is to maintain sedation and ventilate the patient on an intensive care unit until muscle function has returned. Blood testing for cholinesterase function can be performed.
Mivacurium, a non-depolarising neuromuscular blocking drug, is also metabolised via the same route with a similar clinical effect in patients deficient in plasma cholinesterase activity.
Suxamethonium is an odourless, white crystalline substance. Aqueous solutions have a pH of about 4. The dihydrate melts at 160 °C, whereas the anhydrous melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in alcohol (1 gram in about 350 mL), slightly soluble in chloroform, and practically insoluble in ether. Suxamethonium is a hygroscopic compound. The compound consists of two acetylcholine molecules that are linked by their acetyl groups.
Suxamethonium was first discovered in 1906 by Reid Hunt and René de M. Taveau. When studying the drug, animals were given curare and thus they missed the neuromuscular blocking properties of suxamethonium. Instead in 1949 an Italian group led by Daniel Bovet was first to describe succinylcholine induced paralysis. The clinical introduction of suxamethonium was described in 1951 by several groups. Papers published by Stephen Thesleff and Otto von Dardel in Sweden are important but also to be mentioned is work by Bruck, Mayrhofer and Hassfurther in Austria, Scurr and Bourne in UK, and Foldes in America.
There are two phases to the blocking effect of suxamethonium.
Phase 1 block
Phase 1 blocking has the principal paralytic effect. Binding of suxamethonium to the nicotinic acetylcholine receptor results in opening of the receptor's monovalent cation channel; a disorganized depolarization of the motor end-plate occurs and calcium is released from the sarcoplasmic reticulum.
Suxamethonium has a longer duration of effect than acetylcholine, and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor, it cannot cause further depolarization.
Calcium is removed from the muscle cell cytoplasm independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculation.
The results are membrane depolarization and transient fasciculations, followed by paralysis.
Phase 2 block
This phase is not abnormal and is a part of its mechanism of action. It is caused by the blood concentration of suxamethonium exceeding the therapeutic window. Desensitization occurs at the nerve terminal, and the myocyte becomes less sensitive to acetylcholine; the membrane repolarizes and cannot be depolarized again.
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- Rod J. Flower (25 March 2011). Rang and Dale's Pharmacology. Elsevier Science Health Science Division. ISBN 978-0-7020-3471-8.
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- "A Chettiyar Problem". The Times of India. 30 July 2006. Retrieved 2011-07-07.
- Pharmacology for Anaesthesia and Intensive Care. 2nd Edition. Peck, Hill & Williams
- Gennaro, Alfonso. Remington: The Science and Practice of Pharmacy, 20th ed. Lippincot, Wiliams and Wilkins, 2000:1336.
- Dorkins, HR (Apr 1982). "Suxamethonium-the development of a modern drug from 1906 to the present day.". Medical history 26 (2): 145–68. doi:10.1017/S0025727300041132. PMC 1139149. PMID 7047939.