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| Pronunciation | /ˌsʌksɪnɪlˈkoʊliːn/ |
| Trade names | Quelicin, Anectine, others |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | Intravenous,intramuscular |
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| Bioavailability | NA |
| Metabolism | Bypseudocholinesterase, tosuccinylmonocholine andcholine |
| Onset of action | 30–60 sec (IV), 2–3 min (IM) |
| Duration of action | < 10 min (IV), 10–30 min (IM) |
| Excretion | Kidney (10%) |
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| Chemical and physical data | |
| Formula | C14H30Cl2N2O4 |
| Molar mass | 361.30 g·mol−1 |
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Suxamethonium chloride (brand namesScoline andSucostrin, among others), also known assuxamethonium orsuccinylcholine, or simplysux in medical abbreviation,[5] is a medication used to cause short-termparalysis as part ofgeneral anesthesia.[6] This is done to help withtracheal intubation orelectroconvulsive therapy.[6] It is administered by injection, eitherinto a vein orinto a muscle.[7] When used in a vein, onset of action is generally within one minute and effects last for up to 10 minutes.[7]
Common side effects includelow blood pressure, increasedsaliva production,muscle pain, and rash.[7] Serious side effects includemalignant hyperthermia,hyperkalemia andallergic reactions.[8][9] It is not recommended in people who are at risk of high blood potassium or a history ofmyopathy.[6] Use duringpregnancy appears to be safe for the baby.[10]
Suxamethonium is in theneuromuscular blocker family of medications and is of thedepolarizing type.[7] It works by blocking the action ofacetylcholine onskeletal muscles.[7]
Suxamethonium was described as early as 1906 and came into medical use in 1951.[5] It is on theWorld Health Organization's List of Essential Medicines.[11] Suxamethonium is available as ageneric medication.[7]
Succinylcholine chloride injection isindicated, in addition to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.[9]
Its medical uses are limited to short-term muscle relaxation inanesthesia and intensive care, usually for facilitation ofendotracheal intubation. It is popular in emergency medicine due to its rapid onset and brief duration of action. The former is a major point of consideration in the context oftrauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the person cannot beventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing beforelow blood oxygen levels occurs. It may be better thanrocuronium in people without contraindications due to its faster onset of action and shorter duration of action.[12]
Suxamethonium is also commonly used as the solemuscle relaxant duringelectroconvulsive therapy, favoured for its short duration of action.[13]
Suxamethonium is quickly degraded by plasmabutyrylcholinesterase 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 the case in liver failure or in neonates.[14]
The vials are usually stored at a temperature between 2–8 °C, but issues have been reported with lower storage temperatures.[15] The multi-dose vials are stable for up to 14 days at room temperature without significant loss of potency.[4] Unless otherwise indicated in the prescribing information, room temperature for storage of medications is 15–25 °C (59–77 °F).[16]
Side effects includemalignant hyperthermia, muscle pains, acuterhabdomyolysis withhigh blood levels of potassium,[14] transientocular hypertension,constipation[17] and changes in cardiac rhythm, includingslow heart rate, andcardiac arrest. In people with neuromuscular disease orburns, an injection of suxamethonium can lead to a large release ofpotassium fromskeletal muscles, potentially resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns,closed head injury,acidosis,Guillain–Barré syndrome, cerebralstroke,drowning, severe intra-abdominalsepsis, massivetrauma,myopathy, andtetanus.
Suxamethonium does not produceunconsciousness oranesthesia, 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.[medical citation needed]
The side effect of high blood potassium may occur because the acetylcholinereceptor is propped open, allowing continued flow of potassium ions into theextracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol perliter.The increase is transient in otherwise healthy patients. The normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not generally result in adverse effects below a concentration of 6.5 to 7mEq per liter. Therefore, the increase in serum potassium level is usually not catastrophic in otherwise healthy patients. Severely high blood levels of potassium can cause changes incardiac electrophysiology, which, if severe, can result inarrhythmias and evencardiac arrest.[18][19]
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Malignant hyperthermia (MH) from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscleoxidative metabolism. This overwhelms the body's capacity to supplyoxygen, removecarbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.
Susceptibility to malignant hyperthermia is often inherited as anautosomal dominant disorder, for which there are at least sixgenetic loci of interest, the most prominent being theryanodine receptor gene (RYR1). MH susceptibility isphenotype and genetically related tocentral core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and bymyopathy. MH is usually unmasked byanesthesia, 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 withdantrolene 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 action 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, which 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 atypical genes (Ea, Es, Ef) which can be found in varying combinations with the Eu gene, or other atypical genes (seePseudocholinesterase deficiency). Such genes will result in a longer duration of action of the drug, ranging from 20 minutes up to several hours. Acquired factors that affect plasma cholinesterase activity include pregnancy, liver disease, kidney failure,heart failure,thyrotoxicosis, and cancer, as well as a number of other drugs.[20]
If unrecognized by a clinician it could lead to awareness if anesthesia is discontinued whilst still paralyzed or hypoxemia (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.[medical citation needed]
Mivacurium, a non-depolarizing neuromuscular blocking drug, is also metabolized via the same route with a similar clinical effect in patients deficient in plasma cholinesterase activity.[medical citation needed]
Deliberate induction of conscious apnea using this drug led to its use as a form ofaversion therapy in the 1960s and 1970s in some prison and institutional settings.[21][22][23] This use was discontinued after negative publicity concerning the terrifying effects on subjects of this treatment and ethical questions about the punitive use of painful aversion.[citation needed]
There are two phases to the blocking effect of suxamethonium.
Phase 1 blocking has the principal paralytic effect. Binding of suxamethonium to thenicotinic acetylcholine receptor results in opening of the receptor'sion channel; adepolarization of themotor end-plate occurs andcalcium is released from thesarcoplasmic reticulum leading to initial muscle contration andfasciculations.[24]
In normal skeletal muscle,acetylcholine dissociates from the receptor following depolarization and is rapidly hydrolyzed byacetylcholinesterase. The muscle cell is then ready for the next signal.[24]
Suxamethonium is not hydrolyzed by acetylcholinesterase. By remaining bound to the acetylcholine receptor and maintaining themembrane potential above threshold, it does not allow the muscle cell to completely repolarize. This results in the inability for the voltage gated sodium channels to reset and instead are held in an inactive state leading to an inability to form further action potentials.[24]
Voltage gated calcium channels likely close as the partially depolarised membrane potential remains between -30mV and -60mV, which is below the opening of the voltage gated calcium channel, approximately -10mV. Subsequently calcium is removed from the muscle cellcytoplasm . As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes resulting in muscleflaccidity.[25][26]
The results are membrane depolarization and transient fasciculations, followed by flaccid paralysis.
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While this phase is not abnormal and is a part of its mechanism of action, it is undesirable during surgery[citation needed], due to the inability to depolarize the cell again.[24] Often, patients must be on a ventilator for hours if Phase 2 block occurs.[citation needed] It generally occurs when suxamethonium is administered multiple times, or during an infusion occurring over too much time, but can also occur during an initial bolus if the plasma cholinesterase is abnormal[24] Desensitization may occur at the nerve terminal causing the myocyte to become less sensitive to acetylcholine, resulting in the membrane repolarizing and being unable be depolarized again for a period of time.[24]
Suxamethonium is an odorless, whitecrystalline substance. Aqueous solutions have apH of about 4. Thedihydrate melts at 160 °C, whereas theanhydrous melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble inethyl alcohol (1 gram in about 350 mL), slightly soluble inchloroform, and practically insoluble inether. Suxamethonium is ahygroscopic compound.[27] The compound consists of twoacetylcholine molecules that are linked by theiracetyl groups. It can also be viewed as a centralmoiety ofsuccinic acid with twocholine moieties, one on each end.
Suxamethonium was first discovered in 1906 byReid Hunt and René de M. Taveau.[28] When studying the drug, animals were givencurare and thus they missed the neuromuscular blocking properties of suxamethonium. Instead in 1949 an Italian group led byDaniel 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.[29]
Dubai authorities declared that theassassination of Mahmoud Al-Mabhouh, aHamas operative, was carried out on their soil byMossad agents with the use of suxamethonium chloride injection. Entering Dubai under false passports in 2010, the Mossad agents found al-Mabhouh at a hotel, immobilized him with the drug, electrocuted him, and suffocated him with a pillow. A high concentration of suxamethonium chloride was found in al-Mabhouh's body post-mortem. The incident triggered significant diplomatic crises in the Middle East, Europe, and Australia.[30][31]
It is available in German-speaking countries under the trade name Lysthenon among others.[32]
It is sometimes used in combination withpain medications andsedatives foreuthanasia and immobilization of horses.[citation needed]
This article incorporates text from this source, which is in thepublic domain.
