Pancuronium: Difference between revisions

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{{drugbox |
| IUPAC_name = [(2''S'',3''S'',5''S'',8''R'',9''S'',10''S'',13''S'',14''S'',16''S'',17''R'')-<br>17-acetyloxy-10,13-dimethyl-2,16-bis(1-methyl-<br>3,4,5,6-tetrahydro-2''H''-pyridin-1-yl)-2,3,4,5,6,7,<br>8,9,11,12,14,15,16,17-tetradecahydro-1''H''-<br>cyclopenta[''a'']phenanthren-3-yl] acetate
| image = Pancuronium.svg
| image2 = Pancuronium-3D-vdW.png
| CAS_number = 15500-66-0
| 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 = [[Liver|Hepatic]]
| elimination_half-life = 1.5 to 2.7 hours
| excretion = [[Kidney|Renal]] and biliary
| pregnancy_AU = B2
| pregnancy_US = C
| legal_AU =      <!-- Unscheduled / S2 / S3 / S4  / S8 -->
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = [[Intravenous therapy|Intravenous]]
}}


==Overview==
'''Pancuronium bromide''' is a [[chemical compound]], used in medicine with 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]].
==Mode of action==
Pancuronium is a typical [[depolarisation|non-depolarising]] [[curare]]-mimetic [[muscle relaxant]]. It acts as a [[competitive]] [[acetylcholine]] [[receptor antagonist|antagonist]] on [[neuromuscular junction]]s, displacing acetylcholine (hence competitive) from its post-synaptic [[nicotinic acetylcholine receptor]]s. It is, unlike [[suxamethonium]], a non-depolarising agent, which means, that it causes no spontaneous [[depolarisation]]s upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle [[fasciculation]]s upon administration. Pancuronium has no [[hormone|hormonal]] activity. It exerts slight [[vagolytic]] activity (i.e. diminishing activity of the [[vagus nerve]]) and no [[ganglioplegic]] (i.e., blocking [[ganglion]]s) activity. Pancuronium is a very potent muscle relaxant/curaremimetic, the [[Effective dose|ED95]] (i.e. a dose causing a 95% reduction in muscle activity) being only 60 µg/kg body weight administered [[intravenous therapy|intravenously]]. Usual doses for anesthesiologic muscle relaxation (e.g. for intubation and major surgery) are about 100 µg/kg IV (0.1 mg/kg IV); 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 [[opioid]]s, [[barbiturate]]s, [[inhalation anesthetic]]s).
The effects of pancuronium can be at least partially reversed by [[cholinesterase inhibitor|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.
[[Adverse effect (medicine)|Side effects]] include moderately raised [[heart rate]] and thereby [[arterial pressure]] and cardiac output, excessive [[saliva]]tion, [[apnea]] and [[respiratory depression]], [[rash]]es, [[Flushing (physiology)|flushing]] and [[sweating]]. The muscular relaxation can be dangerous in the seriously ill and it can accumulate leading to extended weakness.
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.<ref>http://www.wweek.com/html/euthanasics.html]</ref>
A consultant neonatologist, Dr Munro, was recently cleared of malpractise by the GMC Fitness to Practise panel after giving 23 times the standard dose of Pancuronium to two neonates. Dr Munro administered 2,000mg of Pancuronium to the babies, who were suffering from Agonal Gasping, after consulting the parents that this would ease pain but hasten death.<ref>{{cite news | publisher = [[The Guardian]] | title = Doctor cleared over baby deaths | date = 11 July 2007 | url = http://www.guardian.co.uk/uklatest/story/0,,-6770960,00.html}}</ref>
==Uses in execution==
===Procedure===
It is also used as one component of a [[lethal injection]] used in [[capital punishment]] in some parts of the [[United States of America|USA]].  If improperly administered it can cause [[sodium thiopental]], commonly used as the anesthetic in the [[Lethal injection|lethal injection process]], to [[precipitate]] and become ineffective.
===Controversy===
Pancuronium bromide has no [[analgesic]] effects, and if this precipitation renders the [[painkiller]] agent 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 blamed improper or insufficient dosages of [[painkiller]] 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"<ref>http://web.amnesty.org/library/print/ENGAMR510242004</ref> and thereby lead observers to conclude that lethal injection is painless, or less [[cruel and unusual punishment|cruel]] than other forms of execution.
It wasn't until September 2007 that 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|US Constitution's]] [[Eighth_Amendment_to_the_United_States_Constitution|Eighth Amendment's]] ban on cruel and unusual punishment<ref>{{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 = September 25, 2007 12:34 a.m. |year= 2007 |publisher= CNN}}</ref>.
==Uses in crime==
Pavulon® was the compound used in "Angel of Death" [[Efren Saldivar]]'s killing spree.<ref>http://www.crimelibrary.com/notorious_murders/angels/efren_saldivar/1.html?sect=9</ref>
==References==
<div class="references-small">
<references/>
*{{fr icon}} {{cite web | title = Pavulon® &ndash; ''Information professionnelle'' <nowiki>[prescribing information]</nowiki> | 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}}
</div>

Revision as of 22:26, 2 July 2014