Pancuronium

drugbox
IUPAC_name = [(2"S",3"S",5"S",8"R",9"S",10"S",13"S",14"S",16"S",17"R")-
17-acetyloxy-10,13-dimethyl-2,16-bis(1-methyl-
3,4,5,6-tetrahydro-2"H"-pyridin-1-yl)-2,3,4,5,6,7,
8,9,11,12,14,15,16,17-tetradecahydro-1"H"-
cyclopenta ["a"] phenanthren-3-yl] acetate

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CAS_number = 16974-53-1
CAS_supplemental =
15500-66-0 (bromide)
ATC_prefix = M03
ATC_suffix = AC01
PubChem = 441289
DrugBank =
C=35 | H=60 | N=2 | O=4
molecular_weight = 572.861 g/mol
bioavailability = NA
protein_bound = 77 to 91%
metabolism = Hepatic
elimination_half-life = 1.5 to 2.7 hours
excretion = Renal and biliary
pregnancy_AU = B2
pregnancy_US = C
legal_AU =
legal_UK = POM
legal_US = Rx-only
routes_of_administration = Intravenous

Pancuronium is a chemical compound, used in medicine as the bromide salt pancuronium bromide. It has the brand name Pavulon (Organon International). It is a muscle relaxant with various purposes. It is one of the drugs administered during a lethal injection in the United States.

Mode of action

Pancuronium is a typical non-depolarizing curare-mimetic muscle relaxant. It acts as a competitive acetylcholine antagonist on neuromuscular junctions, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptors. It is (unlike suxamethonium) a non-depolarizing agent, which means that it causes no spontaneous depolarizations upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculations upon administration. Pancuronium has no hormonal activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve) and no ganglioplegic (i.e. blocking ganglions) activity. Pancuronium is a very potent muscle relaxant/curaremimetic. The ED95 (i.e. a dose causing a 95% reduction in muscle activity) is only 60 µg/kg body weight administered intravenously. Muscle relaxation suitable for intubation sets in about 90–120 seconds after administration of the drug. Full muscle paralysis for major surgery is achieved about 2–4 minutes post application. 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, but can be protracted to more hours in poor health subjects and when concomitantly administered with other long-acting anesthetics (e.g. some opioids, barbiturates, inhalation anesthetics).The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine, pyridostigmine and edrophonium.

Uses in medicine

Pancuronium is used with general anaesthesia 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. [ [http://www.wweek.com/html/euthanasics.html euthanasics ] ]

In 1997, Dr 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. Dr Munro administered 2,000 mg of pancuronium to the babies after advising the parents that this would ease their suffering, but could also hasten death. [http://news.bbc.co.uk/1/hi/scotland/north_east/6291224.stm] [cite news | publisher = The Guardian | title = Doctor cleared over baby deaths | date = 11 July 2007] It is on record that neither of the children's parents were unhappy with Dr Munro's treatment of their babies. [http://news.bbc.co.uk/1/hi/scotland/north_east/6276900.stm]

Uses in execution

Procedure

It is also used as one component of a lethal injection used in capital punishment in some parts of the USA. [ [http://news.bbc.co.uk/1/hi/world/americas/7350982.stm BBC article on lethal injection.] Small panel lists the chemicals used.]

Controversy

Pancuronium bromide has no hypnotic effects, and if the anaesthetic agent used in lethal injection is ineffective, an individual could conceivably never achieve unconsciousness, and thus be able to feel all of the pain associated with the procedure, but unable to cry out or move due to the pancuronium's complete paralytic action. There have also been several high-profile civil lawsuits alleging similar failures to achieve analgesia or unconsciousness prior to a general surgical procedures. These too have largely been blamed on improper or insufficient dosages of anaesthetic in concert with normal dosages of pancuronium bromide.

Largely echoing this sentiment, 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" [ [http://web.amnesty.org/library/print/ENGAMR510242004 Amnesty International ] ] and thereby lead observers to conclude that lethal injection is painless, or less cruel than other forms of execution.

In September 2007 the US Supreme Court agreed to hear their first case of whether or not the use of lethal injection does in fact violate the US Constitution's Eighth Amendment's ban on cruel and unusual punishment. [cite web|url=http://www.cnn.com/2007/US/law/09/25/scotus.roundup.ap/index.html#cnnSTCText |title=Court to decide lethal injection, voter ID cases |accessdate=2007-09-25 |year=2007 |publisher=CNN ] On April 16, 2008, the court upheld the constitutionality of Kentucky's lethal injection practices. [cite web| url=http://www.supremecourtus.gov/opinions/07pdf/07-5439.pdf|title= US Supreme Court published opinions |year=2008 |publisher=US Supreme Court]

Uses in crime

Pancuronium was the compound used in Efren Saldivar's killing spree. [ [http://www.crimelibrary.com/notorious_murders/angels/efren_saldivar/1.html?sect=9 Crimelibrary] ] It was also used by paramedics, the "Skin Hunters", to kill patients in the Polish city of Łódź.

Uses in TV crime

Used in a CSI-Miami episode to mimic respiratory failure by a serial killer doctor.

References

External links

*fr icon cite web | title = Pavulon – "Information professionnelle" [prescribing information] | date = December 12, 2005 | url = http://www.kompendium.ch/Monographie.aspx?Id=1c7987b9-38cc-481e-997d-9e23913c9ddf&lang=fr&MonType=fi | publisher = "Compendium Suisse des Médicaments" | accessdate = 2006-10-15 | format = PDF