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{{Short description|Aminosteroid muscle relaxant}} |
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{{drugbox | |
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{{drugbox |
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| IUPAC_name = phenanthren-3-yl] acetate |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 413064551 |
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| IUPAC_name = phenanthren-3-yl] acetate |
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| image = Pancuronium.svg |
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| image = Pancuronium.svg |
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| image2 = Pancuronium-3D-sticks.png |
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| image2 = Pancuronium-3D-sticks.png |
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| drug_name = Pancuronium |
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| CAS_number = 16974-53-1 |
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| CAS_supplemental = <br>15500-66-0 (bromide) |
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<!--Clinical data--> |
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| ATC_prefix = M03 |
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| Drugs.com = {{drugs.com|monograph|pancuronium-bromide}} |
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| ATC_suffix = AC01 |
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| PubChem = 441289 |
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| DrugBank = DB01337 |
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| KEGG = D00492 |
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| C=35 | H=60 | N=2 | O=4 |
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| molecular_weight = 572.861 g/mol |
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| bioavailability = NA |
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| protein_bound = 77 to 91% |
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| metabolism = ] |
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| elimination_half-life = 1.5 to 2.7 hours |
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| excretion = ] and biliary |
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| pregnancy_AU = B2 |
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| pregnancy_AU = B2 |
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| pregnancy_US = C |
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| pregnancy_US = C |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 --> |
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| legal_AU = S4 |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| routes_of_administration = ] |
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| routes_of_administration = ] |
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}} |
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<!--Pharmacokinetic data--> |
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'''Pancuronium''' ('''Pavulon''') is a ] with various purposes. It is the second of three drugs administered during most ]s in the United States. |
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| bioavailability = NA |
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| protein_bound = 77 to 91% |
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| metabolism = ] |
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| elimination_half-life = 1.5 to 2.7 hours |
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| excretion = ] and biliary |
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<!--Identifiers--> |
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== Mode of action == |
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| index2_label = bromide |
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| CAS_number2_Ref = {{cascite|correct|CAS}} |
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| CAS_number2 = 15500-66-0 |
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| UNII2_Ref = {{fdacite|correct|FDA}} |
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| UNII2 = U9LY9Y75X2 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 16974-53-1 |
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| CAS_supplemental = |
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| ATC_prefix = M03 |
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| ATC_suffix = AC01 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 7908 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C35H60N2O4.2BrH/c1-24(38)40-32-21-26-13-14-27-28(35(26,4)23-31(32)37(6)19-11-8-12-20-37)15-16-34(3)29(27)22-30(33(34)41-25(2)39)36(5)17-9-7-10-18-36;;/h26-33H,7-23H2,1-6H3;2*1H/q+2;;/p-2/t26-,27+,28-,29-,30-,31-,32-,33-,34-,35-;;/m0../s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = NPIJXCQZLFKBMV-YTGGZNJNSA-L |
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| PubChem = 441289 |
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| IUPHAR_ligand = 4001 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01337 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 25453 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = J76UF062FS |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00492 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 185073 |
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<!--Chemical data--> |
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Pancuronium is a typical ] ]-mimetic ]. It acts as a ] ] ] on ]s, displacing acetylcholine (hence competitive) from its post-synaptic ]s. It is (unlike ]) a non-depolarizing agent, which means that it causes no spontaneous ]s upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle ]s upon administration. Despite being a ], pancuronium has no ] activity. It exerts slight ] activity (i.e. diminishing activity of the ]) and no ] (i.e. blocking ]s) activity. Pancuronium is a very potent muscle relaxant/curaremimetic. The ] (i.e. a dose causing a 95% reduction in muscle activity) is only 60 µg/kg body weight administered ]. Muscle relaxation suitable for ] sets in about 90–120 seconds after administration of the drug. Full muscle paralysis for major surgery is achieved about 2–4 minutes after 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 ]s, ]s, ]s). |
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| C=35 | H=60 | N=2 | O=4 |
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The effects of pancuronium can be at least partially reversed by ], such as ], ] and ]. |
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}} |
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==Development== |
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Pancuronium is designed to be like two molecules of ] with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance). |
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] and ] also have this same interonium distance. |
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'''Pancuronium''' (trademarked as '''Pavulon''') is an ] ] with various medical uses.<ref name="pmid30855929">{{cite book | vauthors = Das GN, Sharma P, Maani CV | chapter = Pancuronium | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK538346/ | date = January 2021 | pmid = 30855929 }}</ref> It is used in ] and is used in some states as the second of three drugs administered during ]s in the United States. |
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== Uses in medicine == |
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==Mechanism of action== |
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Pancuronium is used with ] in surgery for muscle relaxation and as an aid to ] or ventilation. It does not have ] or ] effects. |
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Pancuronium is a typical ] ]-mimetic ]. It ] the ] at the ] by blocking the binding of ]. It has slight ] activity, causing an increase in heart rate, but no ] (i.e., blocking ]s) activity. It is a very potent muscle relaxant drug, with an ] (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. |
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The effects of pancuronium can be at least partially reversed by ], such as ], ], and ]. |
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] include moderately raised ] and thereby ] and cardiac output, excessive ]tion, ] and ], ]es, ] and ]. 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. |
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==Development== |
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In ] and the ], pancuronium is recommended in the protocol for ]. After administering ] to induce coma, pancuronium is delivered in order to stop breathing.<ref></ref> |
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Workers at ] were inspired by the structure of the aminosteroid alkaloid ] to develop a series of aminosteroid neuromuscular blockers based on an ] nucleus, culminating in the development of pancuronium bromide.<ref>{{cite journal | vauthors = Lewis JJ, Martin-Smith M, Muir TC, Ross HH | title = Steroidal monoquaternary ammonium salts with non-depolarizing neuromuscular blocking activity | journal = The Journal of Pharmacy and Pharmacology | volume = 19 | issue = 8 | pages = 502–508 | date = August 1967 | pmid = 4382437 | doi = 10.1111/j.2042-7158.1967.tb09579.x | s2cid = 2938040 }}</ref><ref>{{cite journal | vauthors = Buckett WR, Hewett CL, Savage DS | title = Pancuronium bromide and other steroidal neuromuscular blocking agents containing acetylcholine fragments | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 10 | pages = 1116–1124 | date = October 1973 | pmid = 4356139 | doi = 10.1021/jm00268a011 }}</ref><ref>{{cite journal | vauthors = McKenzie AG | title = Prelude to pancuronium and vecuronium | journal = Anaesthesia | volume = 55 | issue = 6 | pages = 551–556 | date = June 2000 | pmid = 10866718 | doi = 10.1046/j.1365-2044.2000.01423.x | s2cid = 22476701 }}</ref> |
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Pancuronium is designed to mimic the action of two molecules of ] with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance). |
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In 2007, Dr Michael Munro, a Scottish ] at ] Maternity Hospital, was cleared of malpractice by the ] Fitness to Practice panel after giving 23 times the standard dose of pancuronium to two dying ]s. In the final minutes of life, each baby was suffering from ] and violent body spasms, which was highly distressing for the parents to witness. Dr Munro then administered pancuronium to the babies after advising the parents that this would ease their suffering, but could also hasten death.<ref>{{cite news| url=http://news.bbc.co.uk/1/hi/scotland/north_east/6291224.stm | work=BBC News | title=Baby doctor cleared of misconduct | date=2007-07-11 | accessdate=2010-05-21}}</ref><ref>{{cite news | publisher = ] | title = Doctor cleared over baby deaths | date = 11 July 2007}}</ref> It is on record that neither of the children's parents were unhappy with Dr Munro's treatment of their babies.<ref>{{cite news| url=http://news.bbc.co.uk/1/hi/scotland/north_east/6276900.stm | work=BBC News | title=Doctor felt babies were suffering | date=2007-07-09 | accessdate=2010-05-21}}</ref> |
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] and ] also have this same interonium distance. |
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== Uses in execution == |
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==Uses in medicine== |
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Pancuronium is used with ] in surgery for muscle relaxation and as an aid to ] or ventilation. It does not have ] or ] effects. |
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] include moderately raised ] and thereby ] and cardiac output, excessive ]tion, ] and ], ]es, ], and ].{{medcn|date=January 2016}} 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. |
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=== Procedure === |
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In ] and the ], pancuronium is recommended in the protocol for ]. After administering ] to induce coma, pancuronium is delivered in order to stop breathing.<ref>{{cite web |url = http://www.wweek.com/___ALL_OLD_HTML/euthanasics.html |title = Administration and Compounding Of Euthanasic Agents |access-date = 15 July 2008 |url-status = dead |archive-url = https://web.archive.org/web/20080607061147/http://wweek.com/___ALL_OLD_HTML/euthanasics.html |archive-date = 7 June 2008 | publisher = Royal Dutch Society for the Advancement of Pharmacy | location = The Hague | via = ERGO! }}</ref> |
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It is also used as one component of a ] in administration of the ] in some parts of the ].<ref> Small panel lists the chemicals used.</ref> |
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==Uses in execution and suicide== |
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=== Controversy === |
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===Procedure=== |
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Pancuronium bromide has no ] effects, and if the ] 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 ] in concert with normal dosages of pancuronium bromide. |
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Pancuronium is also used as one component of a ] in administration of the ] in some parts of the ].<ref>{{cite web | title = US court backs lethal injection | url = http://news.bbc.co.uk/1/hi/world/americas/7350982.stm | work = BBC News | date = 16 April 2008 }}</ref> |
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===Controversy=== |
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Largely echoing this sentiment, ] has objected to its use in lethal injections on the grounds that it "may mask the condemned prisoner's suffering during the execution"<ref></ref> and thereby lead observers to conclude that lethal injection is painless, or less ] than other forms of execution. |
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Like all non-depolarising muscle relaxants, pancuronium has no effect on level of consciousness. Therefore, if the ] 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. |
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In 2007, Michael Munro, a Scottish ] at ], was cleared of malpractice by the ] Fitness to Practice panel after giving 23 times the standard dose of pancuronium to two dying ]s. Terminally ill, both dying babies were suffering from ] and violent body spasms, which was highly distressing for the parents to witness. Munro then administered pancuronium to the babies after advising the parents that this would ease their suffering and could also hasten death.<ref>{{cite news| url=http://news.bbc.co.uk/1/hi/scotland/north_east/6291224.stm | work=BBC News | title=Baby doctor cleared of misconduct | date= 11 July 2007 | access-date=2010-05-21}}</ref><ref>{{cite news | work = ] | title = Doctor cleared over baby deaths | url = https://www.theguardian.com/society/2007/jul/11/health.medicineandhealth1 | date = 11 July 2007}}</ref> It was on record that neither of the children's parents were unhappy with Munro's treatment.<ref>{{cite news| url=http://news.bbc.co.uk/1/hi/scotland/north_east/6276900.stm | work=BBC News | title=Doctor felt babies were suffering | date= 9 July 2007 | access-date=2010-05-21}}</ref> |
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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 ] ] ban on cruel and unusual punishment.<ref>{{cite news|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 |archiveurl = http://web.archive.org/web/20080112055432/http://www.cnn.com/2007/US/law/09/25/scotus.roundup.ap/index.html#cnnSTCText <!-- Bot retrieved archive --> |archivedate = 2008-01-12}}</ref> On April 16, 2008, the court upheld the constitutionality of Kentucky's lethal injection practices.<ref>{{cite web| url=http://www.supremecourt.gov/opinions/07pdf/07-5439.pdf|format=PDF|title= US Supreme Court published opinions |year=2008 |publisher=US Supreme Court}}</ref> |
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] has objected to its use in lethal injections on the grounds that it "may mask the condemned prisoner's suffering during the execution,"<ref>{{cite web | title = UA 44/04 Death penalty | date = 6 February 2004 | url = http://web.amnesty.org/library/print/ENGAMR510242004 | publisher = Amnesty International| archive-url = https://web.archive.org/web/20040517064412/http://web.amnesty.org/library/print/ENGAMR510242004 | archive-date = 17 May 2004 }}</ref> thereby leading observers to conclude that lethal injection is painless, or less ] than other forms of execution. |
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== Uses in crime == |
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===Export limitations=== |
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Pancuronium was the compound used in ]'s killing spree.<ref></ref> It was also used by the ] to kill patients in the ] city of ]. 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. |
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The United Kingdom bans the export of pancuronium bromide to the United States due to its use in lethal injections, but not to the Netherlands or Belgium.<ref>{{cite web | title = Provisions supplementing "the torture Regulation" | work = Article 4A of Export Control Order 2008, UK Statutory Instruments 2008 No. 3231 PART 2 Article 9 | publisher = UK Legislation | url = https://www.legislation.gov.uk/uksi/2008/3231/article/9/made }}</ref> |
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==Uses in crime== |
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Pancuronium was used in ]'s killing spree.<ref>{{cite web | vauthors = Ramsland K | date = 9 April 2005 | title = Dark Rumors | url = http://www.crimelibrary.com/notorious_murders/angels/efren_saldivar/1.html?sect=9 | work = Crimelibrary | archive-url = https://web.archive.org/web/20050409164049/http://www.crimelibrary.com/notorious_murders/angels/efren_saldivar/1.html?sect=9 | archive-date=9 April 2005 }}</ref> It was also used by the ] to kill patients in the ] city of ]. Pavulon was also used by ] in 1987 to kill at least ten patients under his care at the ] in New York. |
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== References == |
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== References == |
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{{Reflist|2}} |
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{{Reflist|32em}} |
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== External links == |
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* {{fr icon}} {{cite web | title = Pavulon – ''Information professionnelle'' <nowiki></nowiki> | date = December 12, 2005 | url = http://www.kompendium.ch/Monographie.aspx?Id=bccca93b-f01e-45c2-9040-82d3b4655b0c&lang=fr&MonType=fi | publisher = ''Compendium Suisse des Médicaments'' | accessdate = 2011-01-23 | format = PDF}} |
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</div> |
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{{Muscle relaxants}} |
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{{Muscle relaxants}} |
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{{Nicotinic acetylcholine receptor modulators}} |
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{{Cholinergics}} |
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{{Muscarinic acetylcholine receptor modulators}} |
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