Pancuronium bromide

Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and was originally the second of three drugs administered during lethal injections in the United States.

Pancuronium
Clinical data
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
    Routes of
    administration    		Intravenous
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only)
    • US: ℞-only
    Pharmacokinetic data
    BioavailabilityNA
    Protein binding77 to 91%
    MetabolismHepatic
    Elimination half-life1.5 to 2.7 hours
    ExcretionRenal and biliary
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.035.923
    Chemical and physical data
    FormulaC35H60N2O4
    Molar mass572.861 g/mol g·mol−1
     NY (what is this?)  (verify)

    Mechanism of action

    Pancuronium is a typical non-depolarizing curare-mimetic muscle relaxant. It competitively inhibits the nicotinic acetylcholine receptor at the neuromuscular junction by blocking the binding of acetylcholine. It has slight vagolytic activity, causing an increase in heart rate, but no ganglioplegic (i.e., blocking ganglions) activity. It is a very potent muscle relaxant drug, with an ED95 (i.e., the dose that causes 95% depression of muscle twitch response) of only 60 µg/kg body weight. Onset of action is relatively slow compared to other similar drugs, in part due to its low dose - an intubating dose takes 3–6 minutes for full effect. Clinical effects (muscle activity lower than 25% of physiological) last for about 100 minutes. The time needed for full (over 90% muscle activity) recovery after single administration is about 120–180 minutes in healthy adults. The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine, pyridostigmine, and edrophonium.

    Development

    Pancuronium is designed to mimic the action of two molecules of acetylcholine with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance). Decamethonium and suxamethonium also have this same interonium distance.

    Uses in medicine

    Pancuronium is used with general anesthesia in surgery for muscle relaxation and as an aid to intubation or ventilation. It does not have sedative or analgesic effects.

    Side-effects include moderately raised heart rate and thereby arterial pressure and cardiac output, excessive salivation, apnea and respiratory depression, rashes, flushing, and sweating. The muscular relaxation can be dangerous in the seriously ill and it can accumulate leading to extended weakness. Pancuronium is not preferable in long-term use in ICU-ventilated patients.

    In Belgium and the Netherlands, pancuronium is recommended in the protocol for euthanasia. After administering sodium thiopental to induce coma, pancuronium is delivered in order to stop breathing.[1]

    Uses in execution and suicide

    Procedure

    It is also used as one component of a lethal injection in administration of the death penalty in some parts of the United States.[2]

    Controversy

    Like all non-depolarising muscle relaxants, pancuronium has no effect on level of consciousness. Therefore, if the anaesthetic used is insufficient, the individual may be awake but unable to cry out or move due to the effect of the pancuronium. There have been several civil lawsuits alleging similar failures of adequate anaesthesia during general surgical procedures. These have been largely due to improper or insufficient dosages of anaesthetic in concert with normal dosages of muscle relaxants such as pancuronium.

    In 2007, Michael Munro, a Scottish neonatologist at Aberdeen Maternity Hospital, was cleared of malpractice by the GMC Fitness to Practice panel after giving 23 times the standard dose of pancuronium to two dying neonates. In the final minutes of life, each baby was suffering from agonal gasping and violent body spasms, which was highly distressing for the parents to witness. Munro administered pancuronium to the babies after advising the parents that this would ease their suffering and could also hasten death.[3][4] It is on record that neither of the children's parents was unhappy with Dr Munro's treatment of their babies.[5]

    Amnesty International has objected to its use in lethal injections on the grounds that it "may mask the condemned prisoner's suffering during the execution,"[6] thereby leading observers to conclude that lethal injection is painless, or less cruel than other forms of execution.

    Export limitations

    The United Kingdom bans the export of pancuronium bromide to the United States due to its use in lethal injections.[7]

    Uses in crime

    Pancuronium was used in Efren Saldivar's killing spree.[8] It was also used by the Skin Hunters to kill patients in the Polish city of Łódź. Pavulon was also used by Richard Angelo in 1987 to kill at least 10 patients under his care at the Good Samaritan Hospital in New York.

    References
    1. "Administration and Compounding Of Euthanasic Agents". Archived from the original on 7 June 2008. Retrieved 15 July 2008.
    2. BBC article on lethal injection. Small panel lists the chemicals used.
    3. "Baby doctor cleared of misconduct". BBC News. 2007-07-11. Retrieved 2010-05-21.
    4. "Doctor cleared over baby deaths". The Guardian. 11 July 2007.
    5. "Doctor felt babies were suffering". BBC News. 2007-07-09. Retrieved 2010-05-21.
    6. Amnesty International Archived May 17, 2004, at the Wayback Machine
    7. Article 4A of Export Control Order 2008 - provisions supplementing "the torture Regulation"
    8. Crimelibrary Archived 2005-04-09 at the Wayback Machine
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