Suxamethonium chloride
Encyclopedia
Suxamethonium chloride (INN
), also known as suxamethonium or succinylcholine, is a paralytic drug used to induce muscle relaxation and short-term paralysis, usually to facilitate tracheal intubation
. Suxamethonium is sold under the trade name
s Anectine, Quelicin, and Scoline. It is used as a paralytic agent for euthanasia/immobilization of horses. It is commonly known as "succs" in hospital
(emergency department) settings.
Suxamethonium acts as a depolarizing neuromuscular blocker
. It inhibits the action of acetylcholine
at the neuromuscular junction
, acting non-competitively on muscle-type nicotinic receptors. It is degraded by butyrylcholinesterase
, a plasma cholinesterase. This hydrolysis
by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase
.
, hyperkalaemia, and anaphylaxis, it is perennially popular in emergency medicine because it arguably has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the patient cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before hypoxaemia occurs.
Suxamethonium is also commonly used as the sole muscle relaxant during electroconvulsive therapy
, favoured for its short duration of action.
Suxamethonium is quickly degraded by plasma butyrylcholinesterase
and the duration of effect is usually in the range of a few minutes. When plasma levels of butyrylcholinesterase are greatly diminished or an atypical form is present (an otherwise harmless inherited disorder), paralysis may last much longer.
include malignant hyperthermia
, muscle pains, acute rhabdomyolysis
with hyperkalemia
, transient ocular hypertension
, constipation
and changes in cardiac rhythm including bradycardia
, cardiac arrest
, and ventricular dysrhythmia
s. In patients with neuromuscular disease or burn
s, a single injection of suxamethonium can lead to massive release of potassium
from skeletal muscles, potentially resulting cardiac arrest
. Conditions having susceptibility to suxamethonium-induced hyperkalaemia are burns, closed head injury
, acidosis, Guillain–Barré syndrome, cerebral stroke
, drowning
, severe intraabdominal sepsis
, massive trauma
, myopathy
, and tetanus
.
Suxamethonium does not produce unconsciousness
or anesthesia
, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. For these reasons, administration of the drug to a conscious patient is contraindicated, except in necessary emergency situations.
In Tamil Nadu
anaesthetists ask patients for their caste because many members of the Arya Vaisya Chettiyar
clan, are fatally allergic to Suxamethonium.
. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per litre, whereas the normal range of potassium is 3.5 to 5 mEq per litre. The increase is transient in normal patients. Hyperkalaemia does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per litre.
Severe hyperkalemia
will cause changes in cardiac electrophysiology
, which, if severe, can result in asystole.
Susceptibility to MH is often inherited as an autosomal dominant disorder, for which there are at least 6 genetic loci of interest,[1] most prominent one being the ryanodine receptor gene (RYR1). MH susceptibility is phenotypically and genetically related to central core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is usually unmasked by anesthesia, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with dantrolene sodium is usually initiated; dantrolene and the avoidance of succinylcholine administration in susceptible people have markedly reduced the mortality from this condition.
, although pancuronium bromide is the preferred agent today because of its longer duration of effect and its absence of fasciculation
s as a side-effect. It has also been used for murder by Dr. Carl Coppolino. Suxamethonium was the drug used to murder Nevada State Controller Kathy Augustine
, and was used by surgical technician Kim Hricko in the 1998 murder of her husband Steve. According to Dubai
authorities, Mahmoud al-Mabhouh
was injected with succinylcholine by his attackers before being suffocated
.
line substance. Aqueous solutions have a pH
of about 4. The dihydrate melts at 160 °C, whereas the anhydrous
melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in alcohol
(1 gram in about 350 mL), slightly soluble in chloroform
, and practically insoluble in ether
. Suxamethonium is a hygroscopic compound. The compound consists of two acetylcholine
molecules that are linked by their acetyl
groups.
in Vienna, Austria.
of the motor end-plate occurs and calcium
is released from the sarcoplasmic reticulum.
In normal skeletal muscle, following depolarization, acetylcholine dissociates from the receptor and is rapidly hydrolyzed by acetylcholinesterase and the muscle cell is ready for the next signal.
Suxamethonium has a longer duration of effect than acetylcholine and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential
above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor it cannot cause further depolarization.
Calcium is removed from the muscle cell cytoplasm
independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculation.
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
), also known as suxamethonium or succinylcholine, is a paralytic drug used to induce muscle relaxation and short-term paralysis, usually to facilitate tracheal intubation
Tracheal 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...
. Suxamethonium is sold under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
s Anectine, Quelicin, and Scoline. It is used as a paralytic agent for euthanasia/immobilization of horses. It is commonly known as "succs" in hospital
Hospital
A hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....
(emergency department) settings.
Suxamethonium acts as a depolarizing neuromuscular blocker
Neuromuscular-blocking drugs
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by acting presynaptically via the inhibition of acetylcholine synthesis or release or by acting postsynaptically at the...
. It inhibits the action of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
at the 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...
, acting non-competitively on muscle-type nicotinic receptors. It is degraded by butyrylcholinesterase
Butyrylcholinesterase
Butyrylcholinesterase is a non-specific cholinesterase enzyme that hydrolyses many different choline esters...
, a plasma cholinesterase. This hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
.
Medical uses
Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care, usually for facilitation of endotracheal intubation. Despite its adverse effects, including life threatening malignant hyperthermiaMalignant hyperthermia
Malignant hyperthermia or malignant hyperpyrexia is a rare life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia; specifically, the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine...
, hyperkalaemia, and anaphylaxis, it is perennially popular in emergency medicine because it arguably has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the patient cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before hypoxaemia occurs.
Suxamethonium is also commonly used as the sole muscle relaxant during electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...
, favoured for its short duration of action.
Suxamethonium is quickly degraded by plasma butyrylcholinesterase
Butyrylcholinesterase
Butyrylcholinesterase is a non-specific cholinesterase enzyme that hydrolyses many different choline esters...
and the duration of effect is usually in the range of a few minutes. When plasma levels of butyrylcholinesterase are greatly diminished or an atypical form is present (an otherwise harmless inherited disorder), paralysis may last much longer.
Adverse effects
Side-effectsAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
include malignant hyperthermia
Malignant hyperthermia
Malignant hyperthermia or malignant hyperpyrexia is a rare life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia; specifically, the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine...
, muscle pains, acute rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
with hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
, transient ocular hypertension
Ocular hypertension
Ocular hypertension is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss.Current consensus in ophthalmology defines normal introcular pressure as that between 10 mmHg and 21 mmHg...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and changes in cardiac rhythm including bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
, and ventricular dysrhythmia
Ventricular fibrillation
Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
s. In patients with neuromuscular disease or burn
Burn
A burn is an injury to flesh caused by heat, electricity, chemicals, light, radiation, or friction.Burn may also refer to:*Combustion*Burn , type of watercourses so named in Scotland and north-eastern England...
s, a single injection of suxamethonium can lead to massive release of potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
from skeletal muscles, potentially resulting cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
. Conditions having susceptibility to suxamethonium-induced hyperkalaemia are burns, closed head injury
Closed head injury
Closed head injuries are a type of Traumatic Brain Injury in which the skull and dura mater remain intact. Closed head injuries are the leading cause of death in children under 4 years old and the most common cause of physical disability and cognitive impairment in young people...
, acidosis, Guillain–Barré syndrome, cerebral stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, drowning
Drowning
Drowning is death from asphyxia due to suffocation caused by water entering the lungs and preventing the absorption of oxygen leading to cerebral hypoxia....
, severe intraabdominal sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, massive trauma
Trauma (medicine)
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
, myopathy
Myopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
, and tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
.
Suxamethonium does not produce unconsciousness
Unconsciousness
Unconsciousness is the condition of being not conscious—in a mental state that involves complete or near-complete lack of responsiveness to people and other environmental stimuli. Being in a comatose state or coma is a type of unconsciousness. Fainting due to a drop in blood pressure and a...
or anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. For these reasons, administration of the drug to a conscious patient is contraindicated, except in necessary emergency situations.
In Tamil Nadu
Tamil Nadu
Tamil Nadu is one of the 28 states of India. Its capital and largest city is Chennai. Tamil Nadu lies in the southernmost part of the Indian Peninsula and is bordered by the union territory of Pondicherry, and the states of Kerala, Karnataka, and Andhra Pradesh...
anaesthetists ask patients for their caste because many members of the Arya Vaisya Chettiyar
Chettiar
Chettiar , also spelled Chetty, is a title used by various castes in South India especially in Tamil Nadu. In Kannada, it appears as Setty, Shettar and Shettigar, who are Padmashalis in Andhra Pradesh....
clan, are fatally allergic to Suxamethonium.
Hyperkalemia
The side-effect of hyperkalaemia happens because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluidExtracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...
. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per litre, whereas the normal range of potassium is 3.5 to 5 mEq per litre. The increase is transient in normal patients. Hyperkalaemia does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per litre.
Severe hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
will cause changes in cardiac electrophysiology
Cardiac electrophysiology
Cardiac electrophysiology is the science of elucidating, diagnosing, and treating the electrical activities of the heart. The term is usually used to describe studies of such phenomena by invasive catheter recording of spontaneous activity as well as of cardiac responses to programmed electrical...
, which, if severe, can result in asystole.
Malignant hyperthermia
This side-effect can result from succinylcholine administration in which a drastic and uncontrolled increase in skeletal muscleoxidative metabolism. This overwhelms the body's capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.Susceptibility to MH is often inherited as an autosomal dominant disorder, for which there are at least 6 genetic loci of interest,[1] most prominent one being the ryanodine receptor gene (RYR1). MH susceptibility is phenotypically and genetically related to central core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is usually unmasked by anesthesia, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with dantrolene sodium is usually initiated; dantrolene and the avoidance of succinylcholine administration in susceptible people have markedly reduced the mortality from this condition.
Death
This drug has occasionally been used as a paralyzing agent for executions by 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...
, although pancuronium bromide is the preferred agent today because of its longer duration of effect and its absence of 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 as a side-effect. It has also been used for murder by Dr. Carl Coppolino. Suxamethonium was the drug used to murder Nevada State Controller Kathy Augustine
Kathy Augustine
Kathy Marie Alfano Augustine was a U.S. Republican Party politician from Nevada. She served in the Nevada Assembly and in the Nevada Senate...
, and was used by surgical technician Kim Hricko in the 1998 murder of her husband Steve. According to Dubai
Dubai
Dubai is a city and emirate in the United Arab Emirates . The emirate is located south of the Persian Gulf on the Arabian Peninsula and has the largest population with the second-largest land territory by area of all the emirates, after Abu Dhabi...
authorities, Mahmoud al-Mabhouh
Mahmoud al-Mabhouh
Mahmoud Abdel Rauf al-Mabhouh was a senior Hamas military commander and one of the founders of the Izz ad-Din al-Qassam Brigades, the military affiliate of Hamas...
was injected with succinylcholine by his attackers before being suffocated
Suffocation
Suffocation is the process of Asphyxia.Suffocation may also refer to:* Suffocation , an American death metal band* "Suffocation", a song on Morbid Angel's debut album, Altars of Madness...
.
Chemistry
Suxamethonium is an odourless, white crystalCrystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
line substance. Aqueous solutions have a pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of about 4. The dihydrate melts at 160 °C, whereas the anhydrous
Anhydrous
As a general term, a substance is said to be anhydrous if it contains no water. The way of achieving the anhydrous form differs from one substance to another...
melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
(1 gram in about 350 mL), slightly soluble in chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
, and practically insoluble in ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
. Suxamethonium is a hygroscopic compound. The compound consists of two acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
molecules that are linked by their acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
groups.
History
It has been in use since the pharmacological properties of succinylcholine were discovered around 1950 by K.H. Ginzel, H Klupp, and Gerhard WernerGerhard Werner
Gerhard Werner is a medical doctor and scholar active in research covering areas of pharmacology, psychiatry, cognitive neuroscience, especially neurodynamics, artificial intelligence, and complexity theory...
in Vienna, Austria.
Effects
There are two phases to the blocking effect of suxamethonium; Phase 1 block is the principal paralytic effect.Phase 1 block
Binding of suxamethonium to the nicotinic acetylcholine receptor results in opening of the receptor's monovalent cation channel; a disorganized depolarizationDepolarization
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...
of the motor end-plate occurs and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
is released from the sarcoplasmic reticulum.
In normal skeletal muscle, following depolarization, acetylcholine dissociates from the receptor and is rapidly hydrolyzed by acetylcholinesterase and the muscle cell is ready for the next signal.
Suxamethonium has a longer duration of effect than acetylcholine and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor it cannot cause further depolarization.
Calcium is removed from the muscle cell cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculation.