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 to ...

due to an excess 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 ...

, as a result of the inactivity of the

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

, which normally breaks down acetylcholine.

Signs and symptoms

As a result of cholinergic crisis, the muscles stop responding to the high synaptic levels of acetylcholine, 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 associ ...

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 r ...

, and other signs and symptoms reminiscent of

organophosphate poisoning Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, m ...

. Other symptoms include increased sweating, salivation,

bronchial A bronchus ( ; : bronchi, ) is a passage or airway in the lower respiratory tract that conducts Atmosphere of Earth, air into the lungs. The first or primary bronchi to branch from the trachea at the Carina of trachea, carina are the right main b ...

secretions along with

miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

(constricted pupils). Some of the symptoms 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 cation ...

stimulation include: *

Salivation 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 DN ...

: stimulation of the

salivary glands The salivary glands in many vertebrates including mammals are exocrine glands that produce saliva through a system of Duct (anatomy), ducts. Humans have three paired major salivary glands (Parotid gland, parotid, Submandibular gland, submandibula ...

Lacrimation Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...

: 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 orb ...

(tearing) *

Urination Urination is the release of urine from the bladder through the urethra in Placentalia, placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, v ...

: 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 the necessary biological process by which organisms eliminate a solid, semisolid, or liquid metabolic waste, waste material known as feces (or faeces) from the digestive tract via the anus o ...

Gastrointestinal distress Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory organs of digestion, the liver, ...

Smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

tone changes causing

gastrointestinal problem Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory organs of digestion, the liver, ...

s, including cramping *

Emesis Vomiting (also known as emesis, puking and throwing up) is the 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, gastroenteritis, pregna ...

: Vomiting *

Miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...

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 musc ...

: stimulation of

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

(due to

nicotinic 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 ...

acetylcholine receptor stimulation)

Causes

Cholinergic crisis, sometimes known by the

mnemonic A mnemonic device ( ), memory trick or memory device is any learning technique that aids information retention or retrieval in the human memory, often by associating the information with something that is easier to remember. It makes use of e ...

"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 chemistry, organic chemicals that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of acetylcholinesterase (ACh ...

s, (e.g.,

sarin Sarin (NATO designation GB nerve_agent#G-series.html" ;"title="hort for nerve agent#G-series">G-series, "B" is an extremely toxic organophosphorus compound.VX,

Novichok agent Novichok () is a family of nerve agents, some of which are binary chemical weapons. The agents were developed at the GosNIIOKhT state chemical research institute by the Soviet Union and Russia between 1971 and 1993. Some Novichok agents are ...

s). ** organophosphorus insecticides (e.g.,

parathion Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans, so its use has been ...

aldicarb Aldicarb is a carbamate insecticide which is the active substance in the pesticide Temik. It is effective against thrips, aphids, spider mites, lygus, fleahoppers, and leafminers, but is primarily used as a nematicide. Aldicarb is a cholinest ...

) **

nicotine poisoning Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. Historically, most cases of nicot ...

can be thought of as a subset of cholinergic crisis, as it also involves excessive parasympathetic stimulation. * Ingestion of certain

poisonous fungi This is a compendium of poisonous fungi. See also mushroom poisoning. List of toxic mushroom species ''There are poisonous fungus species listed below.'' List of suspicious mushroom species See also *List of deadly fungi *List of poisonous a ...

(particularly the

muscarine Muscarine, L-(+)-muscarine, or muscarin is a Secondary metabolite, natural product found in certain mushrooms, particularly in ''Inocybe'' and ''Clitocybe'' species, such as the deadly ''Clitocybe dealbata, C. dealbata''. Mushrooms in the g ...

-containing members of the genera ''

Inocybe ''Inocybe'' is a genus of mushroom-forming fungi, with over 1,000 species. Its members are mycorrhizal, and some evidence shows that the high degree of speciation is due to adaptation to different trees and possibly also local habitats. Taxonomy ...

'' and ''

Clitocybe ''Clitocybe'' is a genus of mushrooms characterized by white, off-white, buff, cream, pink, or light-yellow spores, gills running down the stem, and pale white to brown or lilac coloration. They are primarily saprotrophic, decomposing forest grou ...

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

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, ...

who take too high a dose of medications such as

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

s, or seen following

general anaesthesia 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 analges ...

, 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

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 give ...

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

, 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 (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

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

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

neuromuscular-blocking drugs Neuromuscular-blocking drugs, or Neuromuscular blocking agents (NMBAs), block transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcho ...

and

mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...

until the crisis resolves on its own.

References

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