suxamethonium

スキサメトニウム

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/12 20:47:35」(JST)

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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 cat.	A (AU) C (US)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
Routes	Intravenous, Intramuscular
Pharmacokinetic data
Bioavailability	NA
Metabolism	By pseudocholinesterase, to succinylmonocholine and choline
Excretion	Renal (10%)
Identifiers
CAS number	306-40-1 Y
ATC code	M03AB01
PubChem	CID 22475
IUPHAR ligand	4004
DrugBank	DB00202
ChemSpider	21080 Y
UNII	J2R869A8YF Y
KEGG	D00766 Y
ChEBI	CHEBI:61219 Y
ChEMBL	CHEMBL983 Y
Chemical data
Formula	C14H30N2O4
Mol. 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 Y Key:YOEWQQVKRJEPAE-UHFFFAOYSA-L Y
N (what is this?)  (verify)

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 used as a paralytic agent for euthanasia/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.

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 arguably 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 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.

Adverse effects

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.

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.

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, whereas the normal range of potassium is 3.5 to 5 mEq per litre. The increase is transient in normal patients. Hyperkalaemia does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per litre.

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 Apnoea

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.

Death

This drug has occasionally been used as a paralyzing agent for executions by lethal injection, although pancuronium bromide is the preferred agent today because of its longer duration of effect and its absence of fasciculations as a side effect. It has also been used for murder by Dr. Carl Coppolino and Arnfinn Nesset. Suxamethonium was the drug used to murder Nevada State Controller Kathy Augustine, and was used by surgical technician Kim Hricko in the 1998 murder of her husband Steve. According to Dubai authorities, Mahmoud al-Mabhouh was injected with suxamethonium by his attackers before being suffocated. and also used by Genene Jones to murder Chelsea McClellan—just 15 months old and quite possibly many more infants and toddlers.

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. 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.

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.

References

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. 成人における確定診断を得られていない低血圧やショックの評価および初期アプローチ evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
• 3. Rapid sequence induction and intubation (RSII) for anesthesia
• 4. 成人における選択的脊椎手術のための麻酔 anesthesia for elective spine surgery in adults
• 5. 全身麻酔の導入 induction of general anesthesia

English Journal

• Impact of Rocuronium and Succinylcholine on Sedation Initiation After Rapid Sequence Intubation.

• Johnson EG1, Meier A1, Shirakbari A1, Weant K1, Baker Justice S1.
• The Journal of emergency medicine.J Emerg Med.2015 Jul;49(1):43-9. doi: 10.1016/j.jemermed.2014.12.028. Epub 2015 Mar 19.
• BACKGROUND: Rapid sequence intubation (RSI) involves a rapidly acting sedative plus a neuromuscular blocking agent (NMBA) to facilitate endotracheal intubation. Rocuronium and succinylcholine are NMBAs commonly used in RSI with drastically different durations of action.OBJECTIVES: Evaluate whether p
• PMID 25797938
• PMID 25826120

• Effects of adding remifentanil to propofol anesthesia on systemic hemodynamics, cardiac output, and middle cerebral artery flow velocity during electroconvulsive therapy: a pilot study.

• Kadoi Y1, Saito S.
• The journal of ECT.J ECT.2015 Jun;31(2):98-100. doi: 10.1097/YCT.0000000000000202.
• PURPOSE: The purpose of this study was to examine the effects of adding remifentanil to propofol anesthesia on systemic hemodynamics, cardiac output, and middle cerebral artery (MCA) blood flow velocity during electroconvulsive therapy (ECT).METHODS: Twelve patients undergoing ECT were enrolled in t
• PMID 25517395

Japanese Journal

• A randomized trial to identify optimal precurarizing dose of rocuronium to avoid precurarization-induced neuromuscular block

• FUKANO Naoko,SUZUKI Takahiro,ISHIKAWA Kiyoko,MIZUTANI Hitoshi,SAEKI Shigeru,OGAWA Setsuro
• Journal of anesthesia 25(2), 200-204, 2011-04-20
• NAID 10029022389

• がん終末期の幻覚妄想状態に電気痙攣療法が有効であった症例

• 新田 リヱ,平 俊浩,西岡 真美,古口 契児
• Palliative Care Research 6(1), 336-339, 2011
• 【目的】緩和ケア病棟において増悪した幻覚妄想状態に電気痙攣療法(electroconvulsive therapy; ECT)が有効であった症例を経験したので報告する. 【症例】30歳代, 女性. 上行結腸がん再発, 肺転移. 緩和ケア病棟入院18日目に, 幻覚妄想を伴う強い緊張病症状を呈した. 消化管閉塞のため, 内服加療は積極的に行えず, ハロペリドールの点滴加療は奏効しなかった. 患者の苦痛 …
• NAID 130000858769

• ベクロニウムとスキサメトニウムは捨てがたい

• 武田 純三
• 日本臨床麻酔学会誌 = The Journal of Japan Society for Clinical Anesthesia 30(3), 438-445, 2010-05-14
• NAID 10026353655

Related Links

• Suxamethonium - LITFL

Suxamethonium [1 vial $1.90] ADMINISTRATION ROUTES: IV ALTERNATIVE NAMES: aka Succinyl Choline ICU INDICATIONS: 1. Muscle Relaxant (for rapid sequence induction) PRESENTATION AND ADMINISTRATION: IV:

• 「suxamethonium」のプロフィール [pixiv]

pixivに登録すると、suxamethoniumさんの作品に対し評価やコメントをつけたり、メッセージを送り交流することができます。 ... 2014.2.2更新 私はｸｫｰﾀｰﾋﾞｭｰ好きなﾄﾞｯﾀｰで､素人ﾌﾟﾛｸﾞﾗﾏで､医療関係の者です｡甘い ...

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★リンクテーブル★

リンク元	「薬理学」「神経筋接合部」「スキサメトニウム」「脱分極性筋弛緩薬」「脱分極性遮断薬」
拡張検索	「suxamethonium apnea」「suxamethonium poisoning」

「薬理学」

　　[★]

英

pharmacology

関

drug entries

定義

• 生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)

生物系と薬の相互作用

• 薬の生物系に対する相互作用：薬理作用 <-化学の視点
• 生物系の薬に対する相互作用：薬物動態 <-生物の視点

関連分野

• 薬物学 materia medica
• 生薬学
• 実験薬理学
• 臨床薬理学
• 動物薬理学
• 人体薬理学
• 比較薬理学
• 薬理作用学(薬力学)
• 薬物動態学
• 中毒学、毒科学
• 薬物治療学
• 処方学

薬品の命名

Ending of the drug name	Category	Example
～afil	Erectile dysfunction	sildenafil
～ane	Inhalatinal general anesthetic	halothane
～azepam	Benzodiaizepine	diazepam
～azine	Phenothiazine (neuroleptic, antiemetic)	chlorpromazine
～azole	Ailtifungal	ketoconazole
～barbital	Barbiturate	phenobarbital
～caine	Local anesthetic	lidocaine
～cillin	Penicillin	methicillin
～cycline	Antibiotic, protein syntlesis inhibitor	tetracycline
～ipramine	TCA	iimipramine
～navir	Protease inhibitor	saquinavir
～olol	β-antagonist	propranolol
～operidol	Butyrophenone ( neuroleptic )	haloperidol
～oxin	Cardiac glycoside ( inotropic agent )	digoxin
～phylline	Methylxanthine	theophylline
～pril	ACE inhibitor	captopril
～terol	β2 agonist	albuterol
～tidine	H2 antagonist	cimtidine
～triptyline	TCA	amitriptyline
～tropine	Pituitary hormone	somatotropine
～zosin	a1 antagonist	prazosin

薬一覧

神経筋接合部遮断薬(筋弛緩薬)

• 非脱分極性筋弛緩薬 競合的筋弛緩薬

• ベクロニウム vecuronium
• パンクロニウム pancuronium
• アトラクリウム atracurium
• d-ツボクラリン tubocurarine

• 脱分極性筋弛緩薬

• スキサメトニウム suxamethonium
• デカメトニウム decamethonium

交感神経作動薬

→アドレナリン受容体

交感神経遮断薬

→アドレナリン受容体

副交感神経作動薬

→アセチルコリン受容体

副交感神経遮断薬

→アセチルコリン受容体

甲状腺関連物質

• 甲状腺ホルモン製剤

• レボチロキシン levothyroxine
• リオチニシン liothyronine

• 抗甲状腺薬

• プロピルチオウラシル propylthiouracil
• チアマゾール thiamazole

痛風治療薬

• 痛風発作予防薬

• コルヒチン colchicine

• 尿酸排泄促進薬

• ベンズブロマロン benzbromarone
• プロベネシド probenecid

• 尿酸生成抑制薬

• アロプリノール allopurinol

「神経筋接合部」

　　[★]

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。

神経筋接合部に作用する薬物 (GPC.225)

	＋	－
神経活動電位発生		tetrodotoxin
		batrachotoxin
アセチルコリン放出	excess of Ca2+	hemicholinium
		botulinus toxin
		procaine
		Mg2+
		4-aminopyridine
		lack of Ca2+
終板電位発生	succinylcholine(suxamethonium)	curare alkaloids
	decamethonium	α-toxins
アセチルコリン加水分解	cholinesterase inhibitors
筋活動電位発生	veratridine	quinine
		tetrodotoxin
筋収縮		procaine
		dantrolene

「スキサメトニウム」

　　[★]

英

suxamethonium

同

サクシニルコリン succinylcholine、塩化サクシニルコリン succinylcholine chloride, SCC

化

塩化スキサメトニウム　suxamethonium chloride

商

サクシン、レラキシン、Anectin

関

薬理学

[show details]

スキサメトニウム : 約 4,120 件
サクシニルコリン : 約 1,860 件

分類

• 筋弛緩薬

• 脱分極性筋弛緩薬

作用機序

• アセチルコリン受容体に結合してシナプス後膜を脱分極したままにし、興奮伝達を遮断する。

動態

• 血漿中及び肝臓のpseudocholine esterase(偽ChE)によって分解されるので、持続時間が5分と短い

適応

• 麻酔時の筋弛緩

気管内挿管時・骨折脱臼の整復時・喉頭痙攣の筋弛緩

精神神経科における電撃療法の際の筋弛緩

腹部腫瘤診断時

副作用

SAN.71改変

• 1. 筋肉痛：強い攣縮が起こるために筋痛をきたす。

• a) 外眼筋攣縮：眼圧亢進を来たし、緑内障を生ずることがある。この眼圧亢進は投与後1-6分で5-10mmHgほど上昇
• b) 脳圧亢進
• c) 腹筋の攣縮：胃内圧亢進を来たす。　

• 2. 副交感神経刺激：アセチルコリンと同様の作用を有する　→　ムスカリン作用が強く出現し、徐脈、不整脈を起こしやすい
• 3. 高カルシウム血症
• 4. 悪性過高熱(malignant hyperthermia, 悪性高熱)

治療：ダントロレン：筋小胞体からのカルシウム遊離を阻害

「脱分極性筋弛緩薬」

　　[★]

英

depolarizing muscle relaxant

同

脱分極性神経筋遮断薬 depolarizing neuromuscular blocker、脱分極性神経筋接合部遮断薬 depolarizing neuromuscular junction blockingagent

非競合的筋弛緩薬、非競合的神経筋遮断薬、脱分極性神経筋遮断薬　←この使われ方は一般的ではない

関

競合的筋弛緩薬

• スキサメトニウム suxamethonium
• デカメトニウム decamethonium

「脱分極性遮断薬」

　　[★]

英

depolarizing blocking drugs

関

非脱分極性遮断薬、神経筋接合部遮断薬

• スキサメトニウム suxamethonium(サクシニルコリン succinylcholine)

効きが早く、持続時間が長い

• デカメトニウム decamethonium

• 1-2分程度の筋攣縮がおき、Na⁺チャネルが不活化される (第I相遮断)

「suxamethonium apnea」

　　[★] スキサメトニウム無呼吸症

「suxamethonium poisoning」

　　[★] スキサメトニウム中毒