Suxamethonium chloride

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Suxamethonium chloride
Clinical data
Pronunciation/ˌsʌksɪnɪlˈkoʊliːn/
Trade namesQuelicin, Anectine, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: A
intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNA
MetabolismBy pseudocholinesterase, to succinylmonocholine and choline
Onset of action30–60 sec (IV), 2–3 min (IM)
Duration of action< 10 min (IV), 10–30 min (IM)
ExcretionKidney (10%)
Identifiers
  • 2,2'-[(1,4-dioxobutane-1,4-diyl)bis(oxy)]bis
    (N,N,N-trimethylethanaminium)
JSmol)
SMILES
  • [Cl-].[Cl-].O=C(OCC[N+](C)(C)C)CCC(=O)OCC[N+](C)(C)C
  • 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 checkY
  • Key:YOEWQQVKRJEPAE-UHFFFAOYSA-L checkY
 ☒NcheckY (what is this?)  (verify)

Suxamethonium chloride (brand names Scoline and Sucostrin, among others), also known as suxamethonium or succinylcholine, or simply sux in medical abbreviation,

into 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 include

allergic reactions.[8][9] It is not recommended in people who are at risk of high blood potassium or a history of myopathy.[6] Use during pregnancy appears to be safe for the baby.[10]

Suxamethonium is in the

skeletal muscles.[7]

Suxamethonium was described as early as 1906 and came into medical use in 1951.

generic medication.[7]

Medical uses

A vial of suxamethonium chloride

Succinylcholine chloride injection is indicated, 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 in

rocuronium in people without contraindications due to its faster onset of action and shorter duration of action.[12]

Suxamethonium is also commonly used as the sole muscle relaxant during electroconvulsive therapy, favoured for its short duration of action.[13]

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 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

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.[medical citation needed]

Hyperkalemia

The side effect of high blood potassium may occur because the acetylcholine

mEq 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 in cardiac electrophysiology, which, if severe, can result in arrhythmias and even cardiac arrest.[18][19]

Malignant hyperthermia

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 is often inherited as an

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.

Apnea

See also: Pseudocholinesterase deficiency

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 (see

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 of aversion 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]

Mechanism of action

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

motor end-plate occurs and calcium is released from the sarcoplasmic reticulum leading to initial muscle contraction and fasciculations.[24]

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.[24]

Suxamethonium is not hydrolyzed by acetylcholinesterase. By remaining bound to the acetylcholine receptor and maintaining the membrane 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 cell

flaccidity.[25][26]

The results are membrane depolarization and transient fasciculations, followed by flaccid paralysis.

Phase 2 block

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]

Chemistry

Suxamethonium is an odorless, white

acetyl groups. It can also be viewed as a central moiety of succinic acid with two choline
moieties, one on each end.

History

Suxamethonium was first discovered in 1906 by Reid Hunt and René de M. Taveau.[28] 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.[29]

Abuse

assassination of Mahmoud Al-Mabhouh, a Hamas operative, was carried out on their soil by Mossad 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]

Brand names

It is available in German-speaking countries under the trade name Lysthenon among others.[32]

Use in animals

It is sometimes used in combination with pain medications and sedatives for euthanasia and immobilization of horses.[citation needed]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  3. ^ "Anectine- succinylcholine chloride injection, solution". DailyMed. U.S. National Library of Medicine. 17 September 2018. Retrieved 23 November 2020.
  4. ^ a b "Quelicin- succinylcholine chloride injection, solution". DailyMed. U.S. National Library of Medicine. 15 February 2019. Retrieved 23 November 2020.
  5. ^
    PMID 19272538
    .
  6. ^
    ISBN 9789241547659
    .
  7. ^ a b c d e f "Succinylcholine Chloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  8. ^ "Anectine Injection - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 12 January 2016. Archived from the original on 20 December 2016. Retrieved 16 December 2016.
  9. ^ a b "Coronavirus (COVID-19) Update: December 22, 2020". U.S. Food and Drug Administration (Press release). 22 December 2020. Retrieved 23 December 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  10. ^ "Prescribing medicines in pregnancy database". Therapeutic Goods Administration (TGA). 16 December 2016. Archived from the original on 20 December 2016. Retrieved 16 December 2016.
  11. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  12. PMID 26512948
    .
  13. PMID 19222434
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  14. ^
    ISBN 978-0-7020-3471-8. Archived
    from the original on 10 September 2017.
  15. PMID 26787804
    .
  16. ^ "Guidelines for the Storage of Essential Medicines and Other Health Commodities: 3. Maintaining the Quality of Your Products: Controlling temperature". apps.who.int. World Health Organization. Archived from the original on May 25, 2011. Retrieved 2020-03-10.
  17. ^ DiPiro JT, Talbert RL, Yee GC (2005). Matzke Pharmacotherapy: A Pathophysiologicḣ Approach (6th ed.). McGraw-Hill. p. 685.
  18. PMID 29763160
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  19. S2CID 4556150
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  20. ISBN 1-84110-166-4
    .
  21. ^ Reimringer MJ, Morgan SW, Bramwell PF (1970). "Succinylcholine as a modifier of acting-out behavior". Clinical Medicine. 77 (7): 28.
  22. ^ von Hoffman N (5 April 1972). "A Bit of 'Clockwork Orange,' California-Style". Washington Post.
  23. ISBN 0-88405-118-8
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  24. ^
    doi:10.1093/bjaceaccp/mkh002
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  25. PMID 39198449
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  26. PMID 5477644
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  27. ^ Gennaro A (2000). The Science and Practice of Pharmacy (20th ed.). Remington: Lippincott Williams & Wilkins. p. 1336.
  28. ^ Hunt R, De M Taveau R (22 December 1906). "On the physiological action of certain cholin derivatives and new methods for detecting cholin". The British Medical Journal: 1788–1791.
  29. PMID 7047939
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  30. ^ "Dubai Hit: Police Say They Know How Mahmoud al-Mabhouh Was Killed". ABC News.
  31. ^ "Succinylcholine, A Perfect Poison, Makes Appearance in the Dubai Killing". Medgadget. 8 March 2010.
  32. ^ Compendium.ch: LYSTHENON 2% Inj Lös 100 mg/5ml[permanent dead link‍] (in German)
  33. ISBN 978-0-7020-7448-6. Archived from the original
    on 2021-05-18. Retrieved 2021-05-18.
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