Pancuronium (trademarked as Pavulon) is an

aminosteroid Aminosteroids are a group of steroids with a similar structure based on an amino-substituted steroid nucleus. They are neuromuscular blocking agents, acting as competitive antagonists of the nicotinic acetylcholine receptor (nAChR), and block th ...

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therap ...

with various medical uses. It is used in

euthanasia Euthanasia (from el, εὐθανασία 'good death': εὖ, ''eu'' 'well, good' + θάνατος, ''thanatos'' 'death') is the practice of intentionally ending life to eliminate pain and suffering. Different countries have different eut ...

and is used in some states as the second of three drugs administered during

lethal injection Lethal injection is the practice of injecting one or more drugs into a person (typically a barbiturate, paralytic, and potassium solution) for the express purpose of causing rapid death. The main application for this procedure is capital puni ...

s in the United States.

Mechanism of action

Pancuronium is a typical non-depolarizing

curare Curare ( /kʊˈrɑːri/ or /kjʊˈrɑːri/; ''koo-rah-ree'' or ''kyoo-rah-ree'') is a common name for various alkaloid arrow poisons originating from plant extracts. Used as a paralyzing agent by indigenous peoples in Central and South ...

-mimetic

. It competitively inhibits the

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

at the

neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation ...

by blocking the binding of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

. It has slight vagolytic activity, causing an increase in heart rate, but no ganglioplegic (i.e., blocking

ganglion A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympathe ...

s) 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 Neostigmine, sold under the brand name Bloxiverz, among others, is a medication used to treat myasthenia gravis, Ogilvie syndrome, and urinary retention without the presence of a blockage. It is also used in anaesthesia to end the effects of n ...

pyridostigmine Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth ...

, and edrophonium.

Development

Workers at

Organon The ''Organon'' ( grc, Ὄργανον, meaning "instrument, tool, organ") is the standard collection of Aristotle's six works on logical analysis and dialectic. The name ''Organon'' was given by Aristotle's followers, the Peripatetics. The six ...

were inspired by the structure of the aminosteroid alkaloid malouetine to develop a series of aminosteroid neuromuscular blockers based on an

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...

nucleus, culminating in the development of pancuronium bromide. 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). Decamethonium and suxamethonium also have this same interonium distance.

Uses in medicine

Pancuronium is used with

general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

in surgery for muscle relaxation and as an aid to

intubation Intubation (sometimes entubation) is a medical procedure involving the insertion of a tube into the body. Patients are generally anesthetized beforehand. Examples include tracheal intubation, and the balloon tamponade with a Sengstaken-Blake ...

or ventilation. It does not have

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but ...

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

effects. Side-effects include moderately raised

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

and thereby

arterial pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" ...

and cardiac output, excessive

saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can ...

tion,

apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ma ...

and

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapni ...

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

es,

flushing Flushing may refer to: Places * Flushing, Cornwall, a village in the United Kingdom * Flushing, Queens, New York City ** Flushing Bay, a bay off the north shore of Queens ** Flushing Chinatown (法拉盛華埠), a community in Queens ** Flushin ...

, and

sweating Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distri ...

. 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 Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to ...

and the

Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...

, pancuronium is recommended in the protocol for

. After administering sodium thiopental to induce coma, pancuronium is delivered in order to stop breathing.

Uses in execution and suicide

Procedure

Pancuronium is also used as one component of a

in administration of the

death penalty Capital punishment, also known as the death penalty, is the state-sanctioned practice of deliberately killing a person as a punishment for an actual or supposed crime, usually following an authorized, rule-governed process to conclude that ...

in some parts of the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

Controversy

Like all non-depolarising muscle relaxants, pancuronium has no effect on level of consciousness. Therefore, if the

anaesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

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

in concert with normal dosages of muscle relaxants such as pancuronium. In 2007, Michael Munro, a Scottish

neonatologist Neonatology is a subspecialty of pediatrics that consists of the medical care of newborn infants, especially the ill or premature newborn. It is a hospital-based specialty, and is usually practised in neonatal intensive care units (NICUs). The ...

Aberdeen Maternity Hospital Aberdeen Maternity Hospital (AMH) is a specialist maternity hospital in Aberdeen, Scotland. Between 4,000 and 5,000 babies are born at AMH each year. The hospital is located in the Foresterhill area of Aberdeen and serves the region of Grampian ...

, was cleared of malpractice by the GMC Fitness to Practice panel after giving 23 times the standard dose of pancuronium to two dying

neonate An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

s. Terminally ill, both dying babies were 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 and could also hasten death. It is on record that neither of the children's parents were unhappy with Dr Munro's treatment of their babies.

Amnesty International Amnesty International (also referred to as Amnesty or AI) is an international non-governmental organization focused on human rights, with its headquarters in the United Kingdom. The organization says it has more than ten million members and s ...

has objected to its use in lethal injections on the grounds that it "may mask the condemned prisoner's suffering during the execution," thereby leading observers to conclude that lethal injection is painless, or less

cruel Cruelty is the pleasure in inflicting suffering or inaction towards another's suffering when a clear remedy is readily available. Sadism can also be related to this form of action or concept. Cruel ways of inflicting suffering may involve viol ...

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, but not to the Netherlands or Belgium.

Uses in crime

Pancuronium was used in

Efren Saldivar Efren Saldivar (born September 30, 1969) is an American serial killer who murdered patients while working as a respiratory therapist at Adventist Health Glendale, named at that time Glendale Adventist Medical Center in Glendale, California. Ear ...

's killing spree. It was also used by the Skin Hunters to kill patients in the Polish city of

Łódź Łódź, also rendered in English as Lodz, is a city in central Poland and a former industrial centre. It is the capital of Łódź Voivodeship, and is located approximately south-west of Warsaw. The city's coat of arms is an example of ca ...

. Pavulon was also used by

Richard Angelo Richard Angelo (born August 29, 1962) is an American serial killer who operated within Long Island and West Islip, New York. In 1989, he was convicted of murdering several of his patients and sentenced to 61 years to life in prison. Early life ...

in 1987 to kill at least 10 patients under his care at the Good Samaritan Hospital in New York.

References

{{Nicotinic acetylcholine receptor modulators Acetate esters Androstanes Bromides Schering-Plough brands Lethal injection components Muscle relaxants Nicotinic antagonists Piperidines Quaternary ammonium compounds Neuromuscular blockers no:Curare