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a muscle relaxant for striated muscle that is used as an adjunct to anesthesia during certain surgical procedures

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/25 15:48:09」(JST)

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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.^[1]

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.^[2]

Medical uses

A vial of suxamethonium chloride

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 hypoxemia occurs.

Suxamethonium is also commonly used as the sole muscle relaxant during electroconvulsive therapy, favoured for its short duration of action.

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.^[3]

Effects

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.

In normal skeletal muscle, acetylcholine dissociates from the receptor following depolarization and is rapidly hydrolyzed by acetylcholinesterase. The muscle cell is then ready for the next signal.

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.

Adverse effects

Side effects include malignant hyperthermia, muscle pains, acute rhabdomyolysis with hyperkalemia,^[3] transient ocular hypertension, constipation^[4] 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.

In Tamil Nadu, India, it is reported that anaesthetists ask patients for their caste because some members of the Chettiar clan are rumored to be fatally allergic to suxamethonium.^[5]^{[dubious – discuss]}

Hyperkalemia

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.

Severe hyperkalemia will cause changes in cardiac electrophysiology, which, if severe, can result in asystole.

Malignant hyperthermia

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.

Suxamethonium Apnea

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 (see Pseudocholinesterase deficiency). 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.^[6]

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.

Deliberate induction of conscious apnea using this drug led to its use as a form of aversion therapy in the 1960s and 1970s in some prison and institutional settings.^[7]^[8]^[9] This use was discontinued after negative publicity concerning the terrifying effects on subjects of this treatment and ethical questions about use the of punitive use of painful aversion.^{[citation needed]}

Chemistry

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.^[10] The compound consists of two acetylcholine molecules that are linked by their acetyl groups.

History

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.^[11]

References

^ Lee, C; Katz R. (2009). "Clinical implications of new neuromuscular concepts and agents: So long, neostigmine! So long, sux!". J Crit Care 24 (1): 43–9. doi:10.1016/j.jcrc.2008.08.009. PMID 19272538.
^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
^ ^a ^b Rod J. Flower (25 March 2011). Rang and Dale's Pharmacology. Elsevier Science Health Science Division. ISBN 978-0-7020-3471-8.
^ DiPiro, Joseph, et al. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. McGraw-Hill, 2005:685.
^ "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
^ Reimring MJ, Morgan SW, and Bramwell PF. (1970) Succinylcholine as a modifier of acting-out behavior. Clinical Medicine 77(7):28.
^ von Hoffman, Nicholas (1972) "A Bit of 'Clockwork Orange,' California-Style." Washington Post April 5, 1972. mirror
^ Sansweet RJ. (1975) The Punishment Cure. New York: Mason/Charter. ISBN 0-88405-118-8.
^ 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.

UpToDate Contents

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1. 成人における迅速導入気管挿管のための神経筋遮断剤（NMBA） neuromuscular blocking agents nmba for rapid sequence intubation in adults
2. 小児に対する急速挿管法（RSI） rapid sequence intubation rsi in children
3. 成人における双極性障害：薬物治療の催奇形性および出生後のリスク bipolar disorder in adults teratogenic and postnatal risks of pharmacotherapy
4. 出産後女性における双極性障害：治療 bipolar disorder in postpartum women treatment
5. 悪性高熱症：臨床診断および急性期のマネージメント malignant hyperthermia clinical diagnosis and management of acute crisis

English Journal

Sugammadex and rocuronium-induced anaphylaxis.

Takazawa T1, Mitsuhata H2, Mertes PM3.
Journal of anesthesia.J Anesth.2015 Dec 8. [Epub ahead of print]
Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically
PMID 26646837

Succinylcholine resistance.

Ammundsen HB1, Sørensen MK2, Gätke MR2.
British journal of anaesthesia.Br J Anaesth.2015 Dec;115(6):818-21. doi: 10.1093/bja/aev228. Epub 2015 Jul 16.
PMID 26183168

PharmGKB summary: succinylcholine pathway, pharmacokinetics/pharmacodynamics.

Alvarellos ML1, McDonagh EM, Patel S, McLeod HL, Altman RB, Klein TE.
Pharmacogenetics and genomics.Pharmacogenet Genomics.2015 Dec;25(12):622-30. doi: 10.1097/FPC.0000000000000170.
PMID 26398623

Japanese Journal

電気けいれん療法施行中に筋弛緩薬変更を要した悪性症候群の１例

北川寛,伊東あかね,三宅高文,三上敦大,高田秀樹,下舘勇樹
2013-10
… 脱分極性筋弛緩薬であるsuccinylcholineによるNMSの悪化を疑い、４回目の治療から非脱分極性筋弛緩薬のrocuroniumに変更したところ、以後はNMSの悪化なくm-ECTを継続することができた。 …
NAID 120005467298

The Emerging Role of Human Esterases

FUKAMI Tatsuki,YOKOI Tsuyoshi
Drug Metabolism and Pharmacokinetics 27(5), 466-477, 2012
… Paraoxonase and butyrylcholinesterase hydrolyze pirocarpine/simvastatin and succinylcholine/bambuterol, respectively. …
NAID 130004463283

Comparison of recovery times from rocuronium-induced muscle relaxation after reversal with three different doses of sugammadex and succinylcholine during electroconvulsive therapy

KADOI Yuji,HOSHI Hiroko,NISHIDA Akiko,SAITO Shigeru
Journal of anesthesia 25(6), 855-859, 2011-12-20
NAID 10030448788

Related Pictures

★リンクテーブル★

リンク元	「神経筋接合部」「スキサメトニウム」「脱分極性遮断薬」
拡張検索	「succinylcholine apnea」「succinylcholine poisoning」

「神経筋接合部」

Succinylcholine
Systematic (IUPAC) name
	2,2'-[(1,4-dioxobutane-1,4-diyl)bis(oxy)]bis; (N,N,N-trimethylethanaminium)
Clinical data
Trade names	Quelicin
AHFS/Drugs.com	monograph
Pregnancy; category	AU: A; US: C;
Legal status	AU: Prescription Only (S4); UK: POM; US: ℞-only;
Routes of; administration	Intravenous, Intramuscular
Pharmacokinetic data
Bioavailability	NA
Metabolism	By pseudocholinesterase, to succinylmonocholine and choline
Excretion	Renal (10%)
Identifiers
CAS Registry Number	306-40-1
ATC code	M03AB01
PubChem	CID 22475
IUPHAR ligand	4004
DrugBank	DB00202
ChemSpider	21080
UNII	J2R869A8YF
KEGG	D00766
ChEBI	CHEBI:61219
ChEMBL	CHEMBL983
Chemical data
Formula	C14H30N2O4
Molecular mass	290.399 g/mol
	SMILES [Cl-].[Cl-].O=C(OCC[N+](C)(C)C)CCC(=O)OCC[N+](C)(C)C;
	InChI InChI=1S/C14H30N2O4.2ClH/c1-15(2,3)9-11-19-13(17)7-8-14(18)20-12-10-16(4,5)6;;/h7-12H2,1-6H3;2*1H/q+2;;/p-2 ; Key:YOEWQQVKRJEPAE-UHFFFAOYSA-L ;
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　　[★]

英: neuromuscular junction (K)
同: 神経筋シナプス neuromuscular synapse

神経筋接合部は軸索終末，シナプス間隙，筋細胞膜から構成される。