Vecuronium bromide

Vecuronium bromide
Names
Trade namesNorcuron, others
IUPAC name
  • [(2S,3S,5S,8R,9S,10S,13S,14S,16S,17S)-17-Acetyloxy-10,13-dimethyl-16-(1-methyl-3,4,5,6-tetrahydro-2H-pyridin-1-yl)-2-(1-piperidyl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate bromide
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    use    		Intravenous
    Onset of action< 1 min[1]
    Duration of action15 - 30 min[2]
    Defined daily dosenot established[3]
    External links
    AHFS/Drugs.comMonograph
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability100% (IV)
    Metabolismliver 30%
    Elimination half-life51–80 minutes (longer with kidney failure)
    ExcretionFecal (40–75%) and kidney (30% as unchanged drug and metabolites)
    Chemical and physical data
    FormulaC34H57BrN2O4
    Molar mass637.744 g·mol−1
    3D model (JSmol)
    SMILES
    • CC(=O)O[C@H]1C[C@@H]2CC[C@@H]3[C@@H]([C@]2(C[C@@H]1N4CCCCC4)C)CC[C@]5([C@H]3C[C@@H]([C@@H]5OC(=O)C)[N+]6(CCCCC6)C)C.[Br-]
    InChI
    • InChI=1S/C34H57N2O4.BrH/c1-23(37)39-31-20-25-12-13-26-27(34(25,4)22-29(31)35-16-8-6-9-17-35)14-15-33(3)28(26)21-30(32(33)40-24(2)38)36(5)18-10-7-11-19-36;/h25-32H,6-22H2,1-5H3;1H/q+1;/p-1/t25-,26+,27-,28-,29-,30-,31-,32-,33-,34-;/m0./s1 ☒N
    • Key:VEPSYABRBFXYIB-PWXDFCLTSA-M ☒N

    Vecuronium bromide, sold under the brand name Norcuron among others, is a medication used as part of general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation.[1] It is also used to help with endotracheal intubation; however, suxamethonium (succinylcholine) is generally preferred if this needs to be done quickly.[1] It is given by injection into a vein.[1] Effects are greatest at about 4 minutes and last for up to an hour.[1]

    Side effects may include low blood pressure and prolonged paralysis.[4] Allergic reactions are rare.[5] It is unclear if use in pregnancy is safe for the baby.[1] Vecuronium is in the aminosteroid neuromuscular-blocker family of medications and is of the non-depolarizing type.[1] It works by blocking the action of acetylcholine on skeletal muscles.[1]

    Vecuronium was approved for medical use in the United States in 1984.[1] It is on the World Health Organization's List of Essential Medicines.[6] Vecuronium is available as a generic medication.[1] In the United States it is less than US$25 a dose.[2] The effects may be reversed with a combination of neostigmine and atropine.[1]

    Medical uses

    Dosage

    The defined daily dose is not established.[3]

    Mechanism of action

    Vecuronium operates by competing for the cholinoceptors at the motor end plate, thereby exerting its muscle-relaxing properties, which are used adjunctively to general anesthesia. Under balanced anesthesia, the time to recovery to 25% of control (clinical duration) is approximately 25 to 40 minutes after injection and recovery is usually 95% complete approximately 45 to 65 minutes after injection of an intubating dose. The neuromuscular blocking action of vecuronium is slightly enhanced in the presence of potent inhalation anesthetics. If vecuronium is first administered more than 5 minutes after the start of the inhalation of enflurane, isoflurane, or halothane, or when a steady state has been achieved, the intubating dose of vecuronium may be decreased by approximately 15%.

    Vecuronium has an active metabolite, 3-desacetyl-vecuronium, that has 80% of the effect of vecuronium. Accumulation of this metabolite, which is cleared by the kidneys, can prolong the duration of action of the drug, particularly when an infusion is used in a person with kidney failure.[1]

    Reversal of vecuronium can be accomplished by administration of sugammadex which is a γ-cyclodextrin which encapsulates vecuronium preventing it from binding to receptors.[7] Reversal can also be accomplished with neostigmine or other cholinesterase inhibitors, but their efficacy is lower than that of sugammadex.[8]

    History

    As long ago as 1862, adventurer Don Ramon Paez described a Venezuelan poison, guachamaca, which the indigenous peoples used to lace sardines as bait for herons and cranes. If the head and neck of a bird so killed was cut off, the remainder of the flesh could be eaten safely. Paez also described the attempt of a Llanero woman to murder a rival to her lover's affections with guachamaca and unintentionally killed 10 other people when her husband shared his food with their guests.[9] It is probable that the plant was Malouetia nitida or Malouetia schomburgki.[10]

    The genus Malouetia (Family Apocynaceae) is found in both South America and Africa. The botanist Robert E. Woodson Jr comprehensively classified the American species of Malouetia in 1935. At that time, only one African species of Malouetia was recognised, but the following year Woodson described a second: Malouetia bequaertiana, from the Belgian Congo.[10]

    It was in 1960 that scientists reported the isolation of malouetine from the roots and bark of Malouetia bequaertiana Woodson by means of an ion exchange technique. A pure form of the substance was first synthesised in 1964, and was named pancuronium bromide. The name was derived from p(iperidino)an(drostane)cur(arising)-onium.[10]

    A paper published in 1973 discussed the structure-activity relationships of a series of aminosteroid muscle relaxants, including the mono-quaternary analogue of pancuronium, later called vecuronium.[10]

    Society and culture

    It is commercially available as ampoules containing 4 or 10 mg of the drug in powder form which needs to be dissolved in distilled water prior to being given.

    Non-medical use

    Vecuronium bromide has been used as part of a drug cocktail that prisons in the United States use as a means to put a condemned prisoner to death. Vecuronium is used to paralyze the prisoner and stop his or her breathing, in conjunction with a sedative and potassium chloride to stop the prisoner's heart. Injections of vecuronium bromide without proper sedation allow the person to be fully awake but unable to move in response to pain.[11]

    In 2001, Japanese nurse Daisuke Mori was reported to have murdered 10 patients using vecuronium bromide.[12] He was convicted of murder and was sentenced to life imprisonment.[13]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 "Vecuronium Bromide". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
    2. 1 2 Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 23. ISBN 9781284057560.
    3. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 19 September 2020.
    4. ↑ "NORCURON 10mg - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 4 August 2000. Archived from the original on 20 December 2016. Retrieved 16 December 2016.
    5. ↑ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 431. hdl:10665/44053. ISBN 9789241547659.
    6. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    7. ↑ U.S. Food and Drug Administration. "Bridion (sugammadex) Injection" (PDF). Archived (PDF) from the original on 2021-04-02. Retrieved 2019-12-01.
    8. ↑ Carron, Michele; Zarantonello, Francesco; Tellaroli, Paola; Ori, Carlo (December 2016). "Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials". Journal of Clinical Anesthesia. 35: 1–12. doi:10.1016/j.jclinane.2016.06.018. ISSN 1873-4529. PMID 27871504.
    9. ↑ Páez, Ramón (1862-01-01). Wild Scenes in South America, Or, Life in the Llanos of Venezuela. C. Scribner. pp. 206–208. A dreadful case of poisoning by means of this plant had just occurred at Nutrias soon after our arrival on the Apure which created for a time great excitement even amidst that scattered population
    10. 1 2 3 4 McKenzie, A. G. (2000-06-15). "Prelude to pancuronium and vecuronium". Anaesthesia. 55 (6): 551–556. doi:10.1046/j.1365-2044.2000.01423.x. ISSN 1365-2044. PMID 10866718.
    11. ↑ "One Execution Botched, Oklahoma Delays the Next". The New York Times. April 29, 2014. Archived from the original on 2 May 2014.
    12. ↑ "Japanese nurse kills 10 patients, says wanted to trouble hospital". The Indian Express. 2001-01-10. Archived from the original on 2012-03-09. Retrieved 2008-03-22.
    13. ↑ "Nurse gets life for patient slaying". The Japan Times Weekly. April 10, 2004. Archived from the original on April 1, 2010. Retrieved October 26, 2011.
    Identifiers:
    • "Vecuronium Bromide". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2021-01-15. Retrieved 2020-05-17.
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