Suxamethonium chloride
175719
224732606
2008-07-10T04:40:31Z
Teflon Don
196900
/* Medical uses */
{{drugbox
| IUPAC_name = 2,2'-[(1,4-dioxobutane-1,4-diyl)bis(oxy)]bis<br>(''N'',''N'',''N''-trimethylethanaminium)
| image = Suxamethonium-chloride-2D-skeletal.svg
| CAS_number = 306-40-1
| ATC_prefix = M03
| ATC_suffix = AB01
| ATC_supplemental =
| PubChem = 5314
| DrugBank = APRD00159
| C = 14 | H = 30 | N = 2 | O = 4
| molecular_weight = 290.399 g/mol
| bioavailability = NA
| protein_bound =
| metabolism = By [[pseudocholinesterase]], to [[succinylmonocholine]] and [[choline]]
| elimination_half-life =
| excretion = [[Kidney|Renal]] (10%)
| pregnancy_AU = A
| pregnancy_US = C
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular]]
}}
'''Suxamethonium chloride''' (also known as '''succinylcholine''', '''scoline''', or colloquially as '''sux''') is a medication widely used in [[emergency medicine]] and [[anesthesia]] to induce muscle relaxation, usually to make [[endotracheal intubation]] possible. Suxamethonium is sold under several [[trade name]]s such as '''Anectine''', and may be referred to as "sux" for short.
Suxamethonium acts as a depolarizing [[neuromuscular-blocking drugs|neuromuscular blocker]]. It imitates the action of [[acetylcholine]] at the [[neuromuscular junction]], acting on [[muscle type nicotinic receptor]]s, but it is not degraded by [[acetylcholinesterase]] but by [[butyrylcholinesterase]], a plasma cholinesterase. This hydrolysis by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase.
==Chemistry==
Suxamethonium is a white crystalline substance, it is odourless; solutions have a [[pH]] of about 4, the [[dihydrate]] melts about 160 °C, the [[anhydrous]] melts at about 190 °C; it is highly soluble in water (1 gram in about 1 mL), soluble in [[ethanol|alcohol]] (1 gram in about 350 mL), slightly soluble in [[chloroform]], and practically insoluble in [[diethyl ether|ether]]. Suxamethonium is a [[hygroscopic]] compound.<ref>Gennaro, Alfonso. Remington: The Science and Practice of Pharmacy, 20th ed. Lippincot, Wiliams and Wilkins, 2000:1336.</ref> The compound consists of two [[acetylcholine]] molecules that are linked by their [[acetyl]] groups.
==Effects==
There are two phases to the blocking effect of suxamethonium; Phase 1 block is the principal paralytic effect.
===Phase 1 block===
Binding of suxamethonium to the nicotinic [[acetylcholine receptor]] results in opening of the receptor's nicotinic sodium channel; sodium moves into the cell, a disorganised depolarisation of the motor end plate occurs and calcium is released from the sarcoplasmic reticulum. This results in [[fasciculation]].
In the normal muscle, following depolarisation, [[acetylcholine]] is rapidly hydrolysed by [[acetylcholinesterase]] and the muscle cell is able to 'reset' ready for the next signal.
Suxamethonium has a longer duration of effect than acetylcholine and is not hydrolysed by acetylcholinesterase. It does not allow the muscle cell to 'reset' and keeps the 'new' resting membrane potential below threshold. When [[acetylcholine]] binds to an already depolarised receptor it cannot cause further depolarisation.
Calcium is removed from the muscle cell cytosol independent of repolarisation (depolarisation signalling 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.
===Phase 2 block===
Following infusion or repeated doses of suxamethonium, phase 2 block may occur. The receptor blockade takes on characteristics of a non-depolarising neuromuscular block (ie. [[fade]] in response to nerve stimulation, block can be antagonised by reversal agents and longer duration of blockade).
==Medical uses==
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.
The recent arrival of the cyclodextrin [[sugammadex]] may well render suxamethonium obsolete. [[Sugammadex]] can be used to 'instantly' reverse the effects of longer-acting muscle relaxants, particularly [[rocuronium]]. This means that rocuronium can be given in sufficiently high dose to work quickly, and then reliably reversed when necessary, all without the unwelcome side effects of suxamethonium.
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.
==Side effects==
[[Adverse drug reaction|Side effect]]s include muscle pains, acute [[rhabdomyolysis]] with [[hyperkalemia]], transient [[ocular hypertension]], [[constipation]]<ref>DiPiro, Joseph, et al. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. McGraw-Hill, 2005:685.</ref> and changes in cardiac rhythm including [[bradycardia]], [[cardiac arrest]], and [[Ventricular fibrillation|ventricular dysrhythmia]]s. In patients with neuromuscular disease or burns, a single injection of suxamethonium can lead to massive release of potassium from skeletal muscles with cardiac arrest.
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. For these reasons, administration of the drug to a conscious patient is strongly contraindicated, except in necessary emergency situations.
===Hyperkalemia===
The side effect of [[hyperkalaemia]] is 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 mmol 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 mmol per litre.
Severe [[hyperkalemia]] will causes changes in cardiac electrophysiology, which, if severe, can result in asystole.
===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. William Sybers<ref>{{cite web |url=http://i-mass.com/msmm0401.html |title=i-mass.com : international mass spectrometry web resource |accessdate=2007-08-14 |format= |work=}}</ref> and Dr. Carl Coppolino.<ref>http://www.time.com/time/magazine/article/0,9171,899480,00.html</ref> Suxamethonium was the drug used to murder Nevada State Controller [[Kathy Augustine]].<ref>{{cite news | url = http://seattletimes.nwsource.com/html/nationworld/2003768941_ndig30.html | title = Official's husband gets life for her murder| date = June 30, 2007 | accessdate = 2008-05-15 | publisher = [[Seattle Times]]}}</ref>
==See also==
*[[Malignant hyperthermia]], a rare and potentially fatal side effect of suxamethonium.
*[[Anesthetics]]
==References==
<references/>
==External links==
{{Muscle relaxants}}
<!--Categories-->
[[Category:Anesthetics]]
[[Category:Lethal injection components]]
[[Category:Muscle relaxants]]
[[Category:Nicotinic agonists]]
[[Category:Quaternary ammonium compounds]]
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[[de:Suxamethonium]]
[[es:Succinilcolina]]
[[fr:Suxaméthonium]]
[[it:Succinilcolina]]
[[nl:Succinylcholine]]
[[ja:スキサメトニウム]]
[[pl:Chlorek suksametonium]]
[[ro:Suxametoniu]]