Pancuronium
Encyclopedia
Pancuronium is a muscle relaxant
with various purposes. It is the second of three drugs administered during most lethal injection
s in the United States.
curare
-mimetic muscle relaxant
. It acts as a competitive acetylcholine
antagonist
on neuromuscular junction
s, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptor
s. It is (unlike suxamethonium) a non-depolarizing agent, which means that it causes no spontaneous depolarization
s upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculation
s upon administration. Despite being a steroid
, pancuronium has no 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 ED95
(i.e. a dose causing a 95% reduction in muscle activity) is only 60 µg/kg body weight administered intravenously
. 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 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 opioid
s, barbiturate
s, inhalation anesthetics).
The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine
, pyridostigmine
, and edrophonium
.
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.
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 saliva
tion, apnea
and respiratory depression, rash
es, flushing
, and sweating
. 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.
In 2007, Dr 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. Dr Munro then administered pancuronium to the babies after advising the parents that this would ease their suffering, but could also hasten death. It is on record that neither of the children's parents was unhappy with Dr Munro's treatment of their babies.
in administration of the death penalty in some parts of the United States.
effects, and, if the anaesthetic agent used in lethal injection is ineffective, an individual could, it is presumed, 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 been blamed largely on improper or insufficient dosages of anaesthetic in concert with normal dosages of pancuronium bromide.
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," thereby leading observers to conclude that lethal injection is painless, or less cruel
than other forms of execution.
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 US Constitution's Eighth Amendment's
ban on cruel and unusual punishment. On April 16, 2008, the court upheld the constitutionality of Kentucky's lethal injection practices.
's killing spree. 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.
Muscle relaxant
A muscle relaxant is a drug which 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 therapeutic groups: neuromuscular blockers and spasmolytics...
with various purposes. It is the second of three drugs administered during most lethal injection
Lethal injection
Lethal injection is the practice of injecting a person with a fatal dose of drugs for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide...
s in the United States.
Mode of action
Pancuronium is a typical non-depolarizingDepolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
curare
Curare
Curare is a common name for various arrow poisons originating from South America. The three main types of curare are:* tubocurare...
-mimetic muscle relaxant
Muscle relaxant
A muscle relaxant is a drug which 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 therapeutic groups: neuromuscular blockers and spasmolytics...
. It acts as a competitive acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
on neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
s, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
s. It is (unlike suxamethonium) a non-depolarizing agent, which means that it causes no spontaneous depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
s upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculation
Fasciculation
A fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
s upon administration. Despite being a steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
, pancuronium has no hormonal
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
) and no ganglioplegic (i.e. blocking ganglion
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
s) activity. Pancuronium is a very potent muscle relaxant/curaremimetic. The ED95
Effective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
(i.e. a dose causing a 95% reduction in muscle activity) is only 60 µg/kg body weight administered intravenously
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
. Muscle relaxation suitable for intubation
Intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...
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 opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s, barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
s, inhalation anesthetics).
The effects of pancuronium can be at least partially reversed by anticholinesterasics, such as neostigmine
Neostigmine
Neostigmine is a parasympathomimetic that acts as a reversible acetylcholinesterase inhibitor.- Synthesis :Neostigmine was first synthesized by Aeschlimann and Reinert in 1931....
, pyridostigmine
Pyridostigmine
Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and does not cross the blood-brain barrier, except possibly in stressful conditions.-Mode of action:...
, and edrophonium
Edrophonium
Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction...
.
Development
Pancuronium is designed to be like two molecules of acetylcholineAcetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
with the quaternary nitrogen atoms spaced rigidly apart by the steroid rings at a distance of ten atoms (interonium distance).
Decamethonium
Decamethonium
Decamethonium is a depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralysis.- Pharmacology :...
and suxamethonium also have this same interonium distance.
Uses in medicine
Pancuronium is used with general anaesthesiaGeneral anaesthesia
General anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...
in surgery for muscle relaxation and as an aid to intubation
Intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...
or ventilation. It does not have sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
or analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
effects.
Side-effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
include moderately raised heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
and thereby arterial pressure and cardiac output, excessive saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
tion, apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
and respiratory depression, rash
Rash
A rash is a change of the 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, cracked or blistered, swell and may be painful. The causes, and...
es, flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
, and sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
. 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
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
and the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
, pancuronium is recommended in the protocol for euthanasia
Euthanasia
Euthanasia refers to the practice of intentionally ending a life in order to relieve pain and suffering....
. After administering sodium thiopental
Sodium thiopental
Sodium thiopental, better known as Sodium Pentothal , thiopental, thiopentone sodium, or Trapanal , is a rapid-onset short-acting barbiturate general anaesthetic...
to induce coma, pancuronium is delivered in order to stop breathing.
In 2007, Dr Michael Munro, a Scottish neonatologist at Aberdeen
Aberdeen
Aberdeen is Scotland's third most populous city, one of Scotland's 32 local government council areas and the United Kingdom's 25th most populous city, with an official population estimate of ....
Maternity Hospital, was cleared of malpractice by the GMC
General Medical Council
The General Medical Council registers and regulates doctors practising in the United Kingdom. It has the power to revoke or restrict a doctor's registration if it deems them unfit to practise...
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
Agonal respiration
Agonal respiration is an abnormal pattern of breathing characterized by gasping, labored breathing, accompanied by strange vocalizations and myoclonus. Possible causes include cerebral ischemia, extreme hypoxia or even anoxia...
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. It is on record that neither of the children's parents was unhappy with Dr Munro's treatment of their babies.
Procedure
It is also used as one component of a lethal injectionLethal injection
Lethal injection is the practice of injecting a person with a fatal dose of drugs for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide...
in administration of the death penalty in some parts of the United States.
Controversy
Pancuronium bromide has no hypnoticHypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
effects, and, if the anaesthetic agent used in lethal injection is ineffective, an individual could, it is presumed, 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 been blamed largely on improper or insufficient dosages of anaesthetic in concert with normal dosages of pancuronium bromide.
Echoing this sentiment, Amnesty International
Amnesty International
Amnesty International is an international non-governmental organisation whose stated mission is "to conduct research and generate action to prevent and end grave abuses of human rights, and to demand justice for those whose rights have been violated."Following a publication of Peter Benenson'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
Cruel and unusual punishment
Cruel and unusual punishment is a phrase describing criminal punishment which is considered unacceptable due to the suffering or humiliation it inflicts on the condemned person...
than other forms of execution.
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 US Constitution's Eighth Amendment's
Eighth Amendment to the United States Constitution
The Eighth Amendment to the United States Constitution is the part of the United States Bill of Rights which prohibits the federal government from imposing excessive bail, excessive fines or cruel and unusual punishments. The U.S. Supreme Court has ruled that this amendment's Cruel and Unusual...
ban on cruel and unusual punishment. On April 16, 2008, the court upheld the constitutionality of Kentucky's lethal injection practices.
Uses in crime
Pancuronium is the compound that was used in Efren SaldivarEfren Saldivar
Efren Saldivar is an American serial killer who murdered patients while working as a respiratory therapist.-Early life:...
's killing spree. It was also used by the Skin Hunters
Skin Hunters
The "Skin Hunters" is the media nickname for four hospital casualty workers from the Polish city of Łódź, who were convicted of murdering at least five patients and selling information regarding their deaths to funeral homes. They were apprehended in 2002...
to kill patients in the Polish
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
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.