A cholinergic crisis is an over-stimulation at a

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 ...

due to an excess 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 ...

(ACh), as a result of the inactivity of the AChE

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

, which normally breaks down acetylcholine.

Symptoms and diagnosis

As a result of cholinergic crisis, the muscles stop responding to the high synaptic levels of ACh, leading to

flaccid paralysis Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma). This abnormal condition may be caused by disease or by trauma affecting the nerves associa ...

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...

, and other signs and symptoms reminiscent of

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

poisoning. Other symptoms include increased sweating, salivation,

bronchial A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus ...

secretions along with miosis (constricted pupils). This crisis may be masked by the concomitant use of

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given ...

along with

cholinesterase inhibitor Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the syn ...

medication in order to prevent side effects. Flaccid paralysis resulting from cholinergic crisis can be distinguished from

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, ...

by the use of the drug edrophonium (Tensilon), as it only worsens the paralysis caused by cholinergic crisis but strengthens the muscle response in the case of myasthenia gravis. (Edrophonium is a cholinesterase inhibitor, hence increases the concentration of acetylcholine present). Some of the

symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

of increased

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...

stimulation include: *

Salivation 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 ...

: stimulation of the

salivary glands The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary gl ...

* Lacrimation: stimulation of the

lacrimal glands The lacrimal glands are paired exocrine glands, one for each eye, found in most terrestrial vertebrates and some marine mammals, that secrete the aqueous layer of the tear film. In humans, they are situated in the upper lateral region of each or ...

(tearing) *

Urination Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...

: relaxation of the

internal sphincter muscle of urethra The internal urethral sphincter is a urethral sphincter muscle which constricts the internal urethral orifice. It is located at the junction of the urethra with the urinary bladder and is continuous with the detrusor muscle, but anatomically and f ...

, and contraction of the detrusor muscles *

Defecation Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...

* Gastrointestinal distress:

Smooth muscle Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...

tone changes causing gastrointestinal problems, including cramping *

Emesis Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteriti ...

: Vomiting * Miosis constriction of the pupils of the eye via stimulation of the pupillary constrictor muscles *

Muscle spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle ...

: stimulation of

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...

(due to nicotinic acetylcholine receptor stimulation)

Cause

Cholinergic crisis, sometimes known by the

mnemonic A mnemonic ( ) device, or memory device, is any learning technique that aids information retention or retrieval (remembering) in the human memory for better understanding. Mnemonics make use of elaborative encoding, retrieval cues, and image ...

"SLUDGE syndrome" ( Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress and Emesis), can be a consequence of: * Contamination with - or excessive exposure to - certain chemicals including: **

nerve agent Nerve agents, sometimes also called nerve gases, are a class of organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (AChE), an enzyme that ...

s, (''e.g.''

sarin Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.VX, Novichok agents). ** organophosphorus insecticides (''e.g.''

parathion Parathion, also called parathion-ethyl or diethyl parathion and locally known as "Folidol", is an organophosphate insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, inclu ...

, aldicarb) ** nicotine poisoning can be thought of as a subset of cholinergic crisis, as it also involves excessive parasympathetic stimulation. * Ingestion of certain poisonous fungi (particularly the muscarine-containing members of the genera ''

Amanita The genus ''Amanita'' contains about 600 species of agarics, including some of the most toxic known mushrooms found worldwide, as well as some well-regarded edible species. This genus is responsible for approximately 95% of the fatalities resul ...

'', ''

Inocybe ''Inocybe'' is a large genus of mushroom-forming fungi with over 1400 species, including all forms and variations. Members of ''Inocybe'' are mycorrhizal, and some evidence shows that the high degree of speciation in the genus is due to adaptatio ...

'' and '' Clitocybe''). *In medicine, this is seen in patients with

who take too high a dose of medications such as

s, or seen following

general anaesthesia 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 ...

, when too high a dose of a

drug is given to reverse surgical muscle paralysis.

Treatment

Some elements of the cholinergic crisis can be reversed with antimuscarinic drugs like

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

, but the most dangerous effect - respiratory depression, cannot. The neuromuscular junction, where the brain communicates with muscles (like the

diaphragm Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...

, the main breathing muscle), works by acetylcholine activating nicotinic acetylcholine receptors and leading to muscle contraction. Atropine ''only'' blocks

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end- ...

s (a different receptor class than the nicotinic receptors at the

), so atropine will not improve the muscle strength and ability to breathe in someone with cholinergic crisis. Such a patient will require neuromuscular blocking drugs and

mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move a ...

until the crisis resolves on its own.

References

{{DEFAULTSORT:Cholinergic Crisis Toxicology Neurotransmitters Parasympathomimetics Medicinal chemistry Medical mnemonics

Symptoms and diagnosis

Cause

Treatment

See also

References