Vecuronium bromide

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Vecuronium bromide
Vecuronium bromide.svg
Clinical data
Trade names Norcuron, others
AHFS/Drugs.com Monograph
License data
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 100% (IV)
Metabolism liver 30%
Onset of action < 1 min [2]
Elimination half-life 51–80 minutes (longer with kidney failure)
Duration of action 15–30 min [3]
Excretion Fecal (40–75%) and kidney (30% as unchanged drug and metabolites)
Identifiers
  • [(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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.549 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C34H57BrN2O4
Molar mass 637.744 g·mol−1
3D model (JSmol)
  • 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=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 X mark.svgN
  • Key:VEPSYABRBFXYIB-PWXDFCLTSA-M X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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. [2] It is also used to help with endotracheal intubation; however, agents such as suxamethonium (succinylcholine) or rocuronium are generally preferred if this needs to be done quickly. [2] It is given by injection into a vein. [2] Effects are greatest at about 4 minutes and last for up to an hour. [2]

Contents

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. [2]

Vecuronium is in the aminosteroid neuromuscular-blocker family of medications and is of the non-depolarizing type. [2] It works by competitively blocking the action of acetylcholine on skeletal muscles. [2] The effects may be reversed with sugammadex or a combination of neostigmine and glycopyrrolate. To minimize residual blockade, reversal should only be attempted if some degree of spontaneous recovery has been achieved. [2]

Vecuronium was approved for medical use in the United States in 1984 [2] and is available as a generic medication. [2] It is on the World Health Organization's List of Essential Medicines. [6] [7]

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.[ medical citation needed ] 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.[ medical citation needed ] The neuromuscular blocking action of vecuronium is slightly enhanced in the presence of potent inhalation anesthetics.[ medical citation needed ] 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%.[ medical citation needed ]

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. [2]

Reversal of vecuronium can be accomplished by administration of sugammadex which is a γ-cyclodextrin which encapsulates vecuronium preventing it from binding to receptors. [8] Reversal can also be accomplished with neostigmine or other cholinesterase inhibitors, but their efficacy is lower than that of sugammadex. [9]

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. [10] It is probable that the plant was Malouetia nitida or Malouetia schomburgki. [11]

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 recognized, but the following year Woodson described a second: Malouetia bequaertiana, from the Belgian Congo. [11]

In 1960, scientists reported the isolation of malouetine from the roots and bark of Malouetia bequaertiana Woodson by means of an ion exchange technique. Optimization of the aminosteroid nucleus led to a sequence of synthesized derivatives, ultimately leading to pancuronium bromide in 1964. The name was derived from p(iperidino)an(drostane)cur(arising)-onium. [11]

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. [11]

Society and culture

Vecuronium bromide has been used as part of a drug cocktail that prisons in the United States use for execution by lethal injection. 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. [12]

In 2001, Japanese nurse Daisuke Mori was reported to have murdered 10 patients using vecuronium bromide. [13] He was convicted of murder and was sentenced to life imprisonment. [14]

In 2022, Vanderbilt University Medical Center nurse RaDonda Vaught was convicted of two felony charges in the death of a patient who was mistakenly administered vecuronium bromide, rather than the sedative midazolam, also known as Versed. [15]

Related Research Articles

<span class="mw-page-title-main">Sodium thiopental</span> Barbiturate general anesthetic

Sodium thiopental, also known as Sodium Pentothal, thiopental, thiopentone, or Trapanal, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines, but was supplanted by propofol. Despite this, thiopental is listed as an acceptable alternative to propofol, depending on local availability and cost of these agents. It was the first of three drugs administered during most lethal injections in the United States until the US division of Hospira objected and stopped manufacturing the drug in 2011, and the European Union banned the export of the drug for this purpose. Although thiopental abuse carries a dependency risk, its recreational use is rare.

<span class="mw-page-title-main">Lethal injection</span> Form of execution involving injection of chemicals into the bloodstream

Lethal injection is the practice of injecting one or more drugs into a person for the express purpose of causing rapid death. The main application for this procedure is capital punishment, but the term may also be applied in a broader sense to include euthanasia and other forms of suicide. The drugs cause the person to become unconscious, stops their breathing, and causes a heart arrhythmia, in that order.

<span class="mw-page-title-main">Suxamethonium chloride</span> Chemical compound

Suxamethonium chloride, also known as suxamethonium or succinylcholine, or simply sux in medical abbreviation, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal intubation or electroconvulsive therapy. It is administered by injection, either into a vein or into a muscle. When used in a vein, onset of action is generally within one minute and effects last for up to 10 minutes.

<span class="mw-page-title-main">Pancuronium bromide</span> Aminosteroid muscle relaxant

Pancuronium is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and is used in some states as the second of three drugs administered during lethal injections in the United States.

<span class="mw-page-title-main">Edrophonium</span>

Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction. It is sold under the trade names Tensilon and Enlon.

<span class="mw-page-title-main">Neostigmine</span> Anti-full body paralysis drug treatment

Neostigmine, sold under the brand name Bloxiverz, among others, is a medication used to treat myasthenia gravis, Ogilvie syndrome, and urinary retention without the presence of a blockage. It is also used in anaesthesia to end the effects of non-depolarising neuromuscular blocking medication. It is given by injection either into a vein, muscle, or under the skin. After injection effects are generally greatest within 30 minutes and last up to 4 hours.

<span class="mw-page-title-main">Pyridostigmine</span> Medication used to treat myasthenia gravis and chronic Orthostatic Hypotension

Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.

In anaesthesia and advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration. It differs from other techniques for inducing general anesthesia in that several extra precautions are taken to minimize the time between giving the induction drugs and securing the tube, during which period the patient's airway is essentially unprotected.

<span class="mw-page-title-main">Glycopyrronium bromide</span> Chemical compound

Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is given by mouth, via intravenous injection, on the skin, and via inhalation. It is a synthetic quaternary ammonium compound. The cation, which is the active moiety, is called glycopyrronium (INN) or glycopyrrolate (USAN).

<span class="mw-page-title-main">Neuromuscular-blocking drug</span> Type of paralyzing anesthetic including lepto- and pachycurares

Neuromuscular-blocking drugs, or Neuromuscular blocking agents (NMBAs), block transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.

<span class="mw-page-title-main">Rocuronium bromide</span> Non-depolarizing neuromuscular blocker

Rocuronium bromide is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia to facilitate tracheal intubation by providing skeletal muscle relaxation, most commonly required for surgery or mechanical ventilation. It is used for standard endotracheal intubation, as well as for rapid sequence induction (RSI).

<span class="mw-page-title-main">Atracurium besilate</span> Chemical compound

Atracurium besilate, also known as atracurium besylate, is a medication used in addition to other medications to provide skeletal muscle relaxation during surgery or mechanical ventilation. It can also be used to help with endotracheal intubation but suxamethonium (succinylcholine) is generally preferred if this needs to be done quickly. It is given by injection into a vein. Effects are greatest at about 4 minutes and last for up to an hour.

<span class="mw-page-title-main">Sugammadex</span> Selective relaxant binding agent

Sugammadex, sold under the brand name Bridion, is a medication for the reversal of neuromuscular blockade induced by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA). It is marketed by Merck.

Selective relaxant binding agents (SRBAs) are a new class of drugs that selectively encapsulates and binds neuromuscular blocking agents (NMBAs). The first drug introduction of an SRBA is sugammadex.. SRBAs exert a chelating action that effectively terminates an NMBA ability to bind to nicotinic receptors.

<span class="mw-page-title-main">Gantacurium chloride</span> Chemical compound

Gantacurium chloride is a new experimental neuromuscular blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in surgical anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. Gantacurium is not yet available for widespread clinical use: it is currently undergoing Phase III clinical development.

<span class="mw-page-title-main">Candocuronium iodide</span> Chemical compound

Candocuronium iodide is a aminosteroid neuromuscular-blocking drug. Its use within anesthesia for endotracheal intubation and for providing skeletal muscle relaxation during surgery or mechanical ventilation was briefly evaluated in clinical studies in India, though further development was discontinued due to attendant cardiovascular effects, primarily tachycardia that was about the same as the clinically established pancuronium bromide. Candocuronium demonstrated a short duration in the body, but a rapid onset of action. It had little to no ganglion blocking activity, with a greater potency than pancuronium.

<span class="mw-page-title-main">Postoperative residual curarization</span> Medical condition

Postoperative residual curarization (PORC) or residual neuromuscular blockade (RNMB) is a residual paresis after emergence from general anesthesia that may occur with the use of neuromuscular-blocking drugs. Today residual neuromuscular blockade is defined as a train of four ratio of less than 0.9 when measuring the response to ulnar nerve stimulation at the adductor pollicis muscle using mechanomyography or electromyography. A meta-analysis reported that the incidence of residual neuromuscular paralysis was 41% in patients receiving intermediate neuromuscular blocking agents during anaesthesia. It is possible that > 100,000 patients annually in the USA alone, are at risk of adverse events associated with undetected residual neuromuscular blockade. Neuromuscular function monitoring and the use of the appropriate dosage of sugammadex to reverse blockade produced by rocuronium can reduce the incidence of postoperative residual curarization. In this study, with usual care group receiving reversal with neostigmine resulted in a residual blockade rate of 43%.

<span class="mw-page-title-main">Malouetine</span> Chemical compound

Malouetine is an aminosteroid neuromuscular blocking agent and antinicotinic alkaloid isolated from Malouetia spp.

Neostigmine/glycopyrronium bromide, sold under the brand name Prevduo , is a fixed-dose combination medication used for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. It contains neostigmine as the methylsulfate, a cholinesterase inhibitor, and glycopyrronium bromide, an antimuscarinic agent.

<span class="mw-page-title-main">Neuromuscular drug</span>

Neuromuscular drugs are chemical agents that are used to alter the transmission of nerve impulses to muscles, causing effects such as temporary paralysis of targeted skeletal muscles. Most neuromuscular drugs are available as quaternary ammonium compounds which are derived from acetylcholine (ACh). This allows neuromuscular drugs to act on multiple sites at neuromuscular junctions, mainly as antagonists or agonists of post-junctional nicotinic receptors. Neuromuscular drugs are classified into four main groups, depolarizing neuromuscular blockers, non-depolarizing neuromuscular blockers, acetylcholinesterase inhibitors, and butyrylcholinesterase inhibitors.

References

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  3. Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 23. ISBN   9781284057560.
  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. World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  8. U.S. Food and Drug Administration. "Bridion (sugammadex) Injection" (PDF). Retrieved 1 December 2019.
  9. Carron M, Zarantonello F, Tellaroli P, Ori C (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. PMID   27871504.
  10. Páez R (1 January 1862). 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
  11. 1 2 3 4 McKenzie AG (June 2000). "Prelude to pancuronium and vecuronium". Anaesthesia. 55 (6): 551–556. doi:10.1046/j.1365-2044.2000.01423.x. PMID   10866718. S2CID   22476701.
  12. "One Execution Botched, Oklahoma Delays the Next". The New York Times. 29 April 2014. Archived from the original on 2 May 2014.
  13. "Japanese nurse kills 10 patients, says wanted to trouble hospital". The Indian Express. 10 January 2001. Archived from the original on 9 March 2012. Retrieved 22 March 2008.
  14. "Nurse gets life for patient slaying". The Japan Times Weekly. 10 April 2004. Archived from the original on 1 April 2010. Retrieved 26 October 2011.
  15. "Former nurse found guilty in accidental injection death of 75-year-old patient". NPR. 25 March 2022.