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any of the salts of hydrobromic acid; formerly used as a sedative but now generally replaced by safer drugs

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〈U〉臭化物(鎮静剤・睡眠剤として用いる) / 〈C〉《話》陳腐なことば

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/08 20:09:38」(JST)

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

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.^{[medical citation needed]} 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

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 then administered pancuronium to the babies after advising the parents that this would ease their suffering, but 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.^[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

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

UpToDate Contents

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1. 重症患者における神経筋遮断剤の使用 use of neuromuscular blocking medications in critically ill patients
2. 小児に対する急速挿管法（RSI） rapid sequence intubation rsi in children
3. 成人における迅速導入気管挿管のための神経筋遮断剤（NMBA） neuromuscular blocking agents nmba for rapid sequence intubation in adults
4. 術後肺合併症を減少させるための戦略 strategies to reduce postoperative pulmonary complications
5. 周術期アナフィラキシー：再発反応の評価および予防 perioperative anaphylaxis evaluation and prevention of recurrent reactions

English Journal

The effect of defasciculating doses of pancuronium and atracurium on succinylcholine neuromuscular blockade.

Motamed C1, Philippe D2.
Anesthesiology and pain medicine.Anesth Pain Med.2014 Sep 2;4(4):e18488. doi: 10.5812/aapm.18488. eCollection 2014.
BACKGROUND: A defasciculating dose of non-depolarizing muscle relaxant administered prior succinylcholine decrease its side effects including fasciculations and postoperative myalgias; however it is believed that the dosage of succinylcholine should be increased when such a pre-treatment is used.OBJ
PMID 25337472

Haemodynamic differences between pancuronium and vecuronium in an experimental pig model.

Grong K1, Salminen PR, Stangeland L, Dahle GO.
Veterinary anaesthesia and analgesia.Vet Anaesth Analg.2014 Jul 2. doi: 10.1111/vaa.12198. [Epub ahead of print]
OBJECTIVE: To compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker.STUDY DESIGN: Retrospective, non-randomized comparison.ANIMALS: Norwegian Land Race pigs (Sus scrofa domesticus) weighing mean 42 ± SD 3 kg.METHODS: One h
PMID 24985148

Respiratory mechanics: comparison of Beagle dogs, Göttingen minipigs and Cynomolgus monkeys.

Truchetti G1, Troncy E2, Robichaud A3, Gold L3, Schuessler T3, Maghezzi S4, Bassett L5, Authier S6.
Journal of pharmacological and toxicological methods.J Pharmacol Toxicol Methods.2014 Jul-Aug;70(1):48-54. doi: 10.1016/j.vascn.2014.03.171. Epub 2014 Apr 1.
INTRODUCTION: When the no observed adverse effect level (NOAEL) is determined by respiratory safety pharmacology, follow-up studies are warranted and may include airway resistance and compliance. Respiratory mechanics in commonly used large animal species (Beagle dogs, Cynomolgus monkeys, and Götti
PMID 24704341

Japanese Journal

Flow Injection Potentiometric Determination of Pancuronium Bromide in Pharmaceutical Preparation and Urine Samples Using Modified Carbon Paste Electrodes

Chemical and Pharmaceutical Bulletin 59(2), 254-259, 2011
NAID 130000405524

ラットの末梢自然刺激による延髄後角の侵害受容細胞の応答に及ぼす扁桃体刺激の抑制効果

岩手医科大学歯学雑誌 = Dental journal of Iwate Medical University 33(3), 123-136, 2008-12-19
NAID 120005329198

ラットの末梢自然刺激による延髄後角の侵害受容細胞の応答に及ぼす扁桃体刺激の抑制効果

岩手医科大学歯学雑誌 33(3), 123-136, 2008-12-19
NAID 110007026784

「パンクロニウム」

Pancuronium
Systematic (IUPAC) name
	[(2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-17-Acetyloxy-10,13-dimethyl-2,16-bis(1-methyl-3,4,5,6-tetrahydro-2H-pyridin-1-yl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
Clinical data
AHFS/Drugs.com	Monograph
Pregnancy; category	AU: B2; US: C (Risk not ruled out); ;
Routes of; administration	Intravenous
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	NA
Protein binding	77 to 91%
Metabolism	Hepatic
Biological half-life	1.5 to 2.7 hours
Excretion	Renal and biliary
Identifiers
CAS Number	16974-53-1 ; 15500-66-0 (bromide)
ATC code	M03AC01 (WHO)
PubChem	CID 441289
IUPHAR/BPS	4001
DrugBank	DB01337
ChemSpider	25453
UNII	U9LY9Y75X2
KEGG	D00492
ChEBI	CHEBI:7908
ChEMBL	CHEMBL185073
Chemical data
Formula	C35H60N2O4
Molar mass	572.861 g/mol
	InChI InChI=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 ; Key:NPIJXCQZLFKBMV-YTGGZNJNSA-L ;
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