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Pancuronium (trademarked as Pavulon) is an aminosteroid
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 therapeu ...
with various medical uses. It is used in
euthanasia Euthanasia (from : + ) is the practice of intentionally ending life to eliminate pain and suffering. Different countries have different Legality of euthanasia, euthanasia laws. The British House of Lords Select committee (United Kingdom), se ...
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) for the express purpose of causing death. The main application for this procedure is capital punishment, but t ...
s in the United States.


Mechanism of action

Pancuronium is a typical non-depolarizing curare-mimetic
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 therapeu ...
. It competitively inhibits the
nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...
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 to ...
by blocking the binding of
acetylcholine Acetylcholine (ACh) is an organic compound 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 (: ganglia) 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 ...
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, pyridostigmine, and edrophonium.


Development

Workers at
Organon The ''Organon'' (, 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, who maintained against the ...
were inspired by the structure of the aminosteroid alkaloid malouetine to develop a series of aminosteroid neuromuscular blockers based on an androstane nucleus, culminating in the development of pancuronium bromide. Pancuronium is designed to mimic the action of two molecules of
acetylcholine Acetylcholine (ACh) is an organic compound 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 ...
with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance).
Decamethonium Decamethonium (Syncurine) is a depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralytic, paralysis. Pharmacology Decamethonium, which has a short action time, is similar to acetylcholine and ...
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 medically induced loss of consciousness that renders a patient unarousable even by painful stimuli. It is achieved through medications, which can be injected or inhaled, often with an analgesi ...
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. Most commonly, intubation refers to tracheal intubation, a procedure during which an endotracheal tube is inserted into the trachea to supp ...
or ventilation. It does not have
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
or
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
effects.
Side-effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...
include moderately raised
heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
and thereby arterial pressure and cardiac output, excessive
saliva Saliva (commonly referred as spit or drool) 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 ...
tion,
apnea Apnea (also spelled apnoea in British English) is the temporary 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 ...
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 skin that 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, cracke ...
es, flushing, and
sweating Perspiration, also known as sweat, is the fluid secreted by 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 distributed over much of the ...
. 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, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...
and the
Netherlands , Terminology of the Low Countries, informally Holland, is a country in Northwestern Europe, with Caribbean Netherlands, overseas territories in the Caribbean. It is the largest of the four constituent countries of the Kingdom of the Nether ...
, pancuronium is recommended in the protocol for
euthanasia Euthanasia (from : + ) is the practice of intentionally ending life to eliminate pain and suffering. Different countries have different Legality of euthanasia, euthanasia laws. The British House of Lords Select committee (United Kingdom), se ...
. After administering
sodium thiopental Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of ...
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
lethal injection Lethal injection is the practice of injecting one or more drugs into a person (typically a barbiturate, paralytic, and potassium) for the express purpose of causing death. The main application for this procedure is capital punishment, but t ...
in administration of the
death penalty Capital punishment, also known as the death penalty and formerly called judicial homicide, is the state-sanctioned killing of a person as punishment for actual or supposed misconduct. The sentence ordering that an offender be punished in s ...
in some parts of the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
.


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 t ...
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
General Medical Council The General Medical Council (GMC) is a public body that maintains the official register of physician, medical practitioners within the United Kingdom. Its chief responsibility is to "protect, promote and maintain the health and safety of the pu ...
Fitness to Practice panel after giving 23 times the standard dose of pancuronium to two dying
neonate In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...
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 was on record that neither of the children's parents were unhappy with Munro's treatment.
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 that it has more than ten million members a ...
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 not painless, or less
cruel Cruelty is the intentional infliction of suffering or the 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 involv ...
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's killing spree. It was also used by the Skin Hunters to kill patients in the Polish city of
Łódź Łódź is a city in central Poland and a former industrial centre. It is the capital of Łódź Voivodeship, and is located south-west of Warsaw. Łódź has a population of 655,279, making it the country's List of cities and towns in Polan ...
. Pavulon was also used by Richard Angelo in 1987 to kill at least ten patients under his care at the Good Samaritan Hospital in New York.


See also

* Malouetine


References

{{Muscarinic acetylcholine receptor modulators Acetate esters Androstanes Bromides Drugs developed by Schering-Plough Lethal injection components M2 receptor antagonists Muscle relaxants Neuromuscular blockers Nicotinic antagonists Piperidines Quaternary ammonium compounds no:Curare