Anticholinergic Medication
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Anticholinergics (anticholinergic agents) are substances that block the action of the
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 ...
(ACh)
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
at
synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...
s in the central and
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...
. These agents inhibit the
parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...
by selectively blocking the binding of ACh to its receptor in
nerve cell A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...
s. The
nerve fiber An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...
s of the parasympathetic system are responsible for the involuntary movement of
smooth muscles 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 becau ...
present in the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
,
urinary tract The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...
,
lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
,
sweat gland Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial s ...
s, and many other parts of the body. In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central and peripheral nervous system and at the neuromuscular junction:
antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...
agents and antinicotinic agents (
ganglionic blockers A ganglionic blocker (or ganglioplegic) is a type of medication that inhibits transmission between preganglionic and postganglionic neurons in the autonomic nervous system, often by acting as a nicotinic receptor antagonist. Nicotinic acetylcholi ...
,
neuromuscular blockers 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 ...
). The term "anticholinergic" is typically used to refer to antimuscarinics that competitively inhibit the binding of ACh to
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; such agents do not antagonize the binding at
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 ...
s 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 ...
, although the term is sometimes used to refer to agents that do so.


Medical uses

Anticholinergic drugs are used to treat a variety of conditions: *
Dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...
(including
vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...
and
motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...
-related symptoms) *
Extrapyramidal symptoms Extrapyramidal symptoms (EPS) are signs and symptoms, symptoms that are wikt:archetypical, archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they ...
, a potential side-effect of antipsychotic medications * Gastrointestinal disorders (e.g.,
peptic ulcers Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...
,
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, pyloro
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 ...
,
diverticulitis Diverticulitis, also called colonic diverticulitis, is a gastrointestinal disease characterized by inflammation of abnormal pouches—Diverticulum, diverticula—that can develop in the wall of the large intestine. Symptoms typically include lo ...
,
ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
, and
vomiting 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, pre ...
) * Genitourinary disorders (e.g.,
cystitis A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (py ...
,
urethritis Urethritis is the inflammation of the urethra. The most common symptoms include painful or difficult urination and urethral discharge. It is a commonly treatable condition usually caused by infection with bacteria. This bacterial infection is ...
, and
prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...
) *
Insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
, although usually only on a short-term basis * Respiratory disorders (e.g.,
asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
,
chronic bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
, and
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
OPD OPD may refer to: Police departments * Oakland Police Department, a U.S. law enforcement agency in California * Omaha Police Department, a U.S. law enforcement agency in Nebraska * Orlando Police Department, a U.S. law enforcement agency in Florida ...
*
Sinus bradycardia Sinus bradycardia is a sinus rhythm with a reduced rate of electrical discharge from the sinoatrial node, resulting in a bradycardia, a heart rate that is lower than the normal range (60–100 beats per minute for adult humans). Signs and sympt ...
due to a hypersensitive
vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
*
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 ...
based
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 ...
poisoning Poisoning is the harmful effect which occurs when Toxicity, toxic substances are introduced into the body. The term "poisoning" is a derivative of poison, a term describing any chemical substance that may harm or kill a living organism upon ...
, such as VX,
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.tabun, and
soman Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...
(atropine is favoured in conjunction with an oxime, usually
pralidoxime Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosph ...
) Anticholinergics generally have
antisialagogue Antisialagogues are drugs or substances that decrease the flow rate of saliva and their effect is opposite to that of sialagogues. Their origin may be both natural and synthetic. Anticholinergics generally have antisialagogue effects, and most pr ...
effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures. Until the beginning of the 20th century, anticholinergic drugs were widely used to treat psychiatric disorders.


Physiological effects

Effects of anticholinergic drugs include: *
Delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
(often with
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s and
delusion A delusion is a fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some other m ...
s indistinguishable from reality) *Ocular symptoms (from
eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...
s):
mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...
, pupil dilation, and
acute angle-closure glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
in those with shallow
anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, ...
*
Anhidrosis Hypohidrosis is a medical condition in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidr ...
, dry mouth, dry skin *
Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
*
Constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
*
Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
*
Urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...
*
Cutaneous Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different d ...
vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
Clinically the most significant feature is
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
, particularly in the elderly, who are most likely to be affected by the
toxidrome A toxidrome (a portmanteau of ''toxic'' and ''syndrome'', coined in 1970 by Mofenson and Greensher) is a syndrome caused by a dangerous level of toxins in the body. It is often the consequence of a drug overdose. Common symptoms include dizziness, ...
.


Cognitive and physical decline

Long-term use may increase the risk of both cognitive and physical decline. It is unclear whether they affect the risk of death generally. However, in older adults they do appear to increase the risk of death. The anticholinergic burden (ACB) approach examines this risk.


Side effects

Possible effects of anticholinergics include: * Poor coordination *
Dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
* Decreased mucus production in the nose and
throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains the Human pharynx, pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the t ...
; consequent dry, sore throat *
Dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...
with possible acceleration of
dental caries Tooth decay, also known as caries,The word 'caries' is a mass noun, and is not a plural of 'carie'.'' is the breakdown of teeth due to acids produced by bacteria. The resulting cavities may be a number of different colors, from yellow to black ...
* Cessation of
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 ...
; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin * Increased
body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...
* Pupil dilation; consequent sensitivity to bright light (
photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...
) * Loss of accommodation (loss of focusing ability, blurred vision –
cycloplegia Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation. Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on nearby objects. This results in ...
) *
Double vision Diplopia is the simultaneous perception of two images of a single object that may be displaced in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often voluntary. However, when occ ...
* Increased heart rate * Tendency to be easily startled *
Urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...
*
Urinary incontinence Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a significant effect on quality of life. Urinary incontinence is common in older women ...
while sleeping * Diminished bowel movement, sometimes
ileus Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction. The word 'ileus' derives . The term 'subileus' refers to a partial obstruction. Signs and symptoms S ...
(decreases motility via the
vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
) * Increased
intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...
; dangerous for people with narrow-angle
glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
Possible effects in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
resemble those associated with
delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...
, and may include: * Confusion * Disorientation * Agitation *
Euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
or
dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and uneas ...
* Respiratory depression * Memory problems * Inability to concentrate * Wandering thoughts; inability to sustain a
train of thought The train of thought or track of thought refers to the interconnection in the sequence of ideas expressed during a connected discourse or thought, as well as the sequence itself, especially in discussion how this sequence leads from one idea to ...
* Incoherent speech * Irritability * Mental confusion (brain fog) * Wakeful myoclonic jerking * Unusual sensitivity to sudden sounds * Illogical thinking *
Photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...
* Visual disturbances ** Periodic flashes of light ** Periodic changes in visual field **
Visual snow Visual snow syndrome (VSS) is an uncommon neurological condition in which the primary symptom is visual snow, a persistent flickering white, black, transparent, or colored dots across the whole visual field. It is distinct from the ''symptom'' ...
** Restricted or "tunnel vision" * Visual, auditory, or other sensory
hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s ** Warping or waving of surfaces and edges ** Textured surfaces ** "Dancing" lines; "spiders", insects;
form constants A form constant is one of several Pattern, geometric patterns which are recurringly observed during hypnagogia, hallucinations and altered states of consciousness. History In 1926, Heinrich Klüver systematically studied the effects of mescalin ...
** Lifelike objects indistinguishable from reality ** Phantom smoking ** Hallucinated presence of people not actually there (e.g.
shadow people A shadow person (also known as a shadow figure or black mass) is a popular subject in circles of the paranormal and supernatural detailing beings resembling animate human shadows, sometimes interpreted as the presence of a spirit. History and ...
) * Rarely: seizures, coma, and death *
Orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...
(severe drop in systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population Older patients are at a higher risk of experiencing CNS side effects. The link possible between anticholinergic medication use and cognitive decline/dementia has been noted in weaker observational studies. Although there is no strong evidence from randomized controlled trials to suggest that these medications should be avoided, clinical guidelines suggest that a consideration be made to decrease the use of these medications if safe to do so and the use of these medications be carefully considered to reduce any possible adverse effects including cognitive decline.


Toxicity

An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible
acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...
agents such as
physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...
can be used as an antidote in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine. Asystole has occurred after physostigmine administration for tricyclic antidepressant overdose, so a conduction delay (QRS > 0.10 second) or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.


Dementia

A recent study carried out by experts from the University of Nottingham and funded by the National Institute for Health Research (NIHR) has shown there to be an increased risk of up to 50% of patients developing Dementia due to some of these medications and cautions have been advised with their use. The study findings showed increased risks of dementia for anticholinergic drugs overall and specifically for the anticholinergic antidepressants, antipsychotic drugs, antiparkinsons drugs, bladder drugs and epilepsy drugs after accounting for other risk factors for dementia. However, in a March 2025 article published in the ''
American Journal of Epidemiology The American Journal of Epidemiology (''AJE'') is a peer-reviewed journal for empirical research findings, opinion pieces, and methodological developments in the field of epidemiological research. The current editor-in-chief is Enrique Schisterma ...
'', Aguado and colleagues reported that anticholinergic
antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...
medications reduced individuals' 10-year
risk In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environ ...
of
incident The Incident Command System (ICS) is a standardized approach to the command, control, and coordination of emergency response providing a common hierarchy within which responders from multiple agencies can be effective. ICS was initially develope ...
vascular dementia Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dement ...
by 31% when used for ≥6 years compared to 3–6 years (
risk ratio The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
, 0.69; 95% CI, 0.54–0.90); the comparative risk of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
was reduced, as well, but not to a
statistically significant In statistical hypothesis testing, a result has statistical significance when a result at least as "extreme" would be very infrequent if the null hypothesis were true. More precisely, a study's defined significance level, denoted by \alpha, is the ...
degree (risk ratio, 0.91; 95% CI, 0.77–1.10).


Pharmacology

Anticholinergics are classified according to the receptors that are affected: * ''
Antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...
'' agents operate on the
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. The majority of anticholinergic drugs are antimuscarinics. * '' Antinicotinic'' agents operate on 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 ...
s. The majority of these are non-depolarising
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 ...
relaxants for surgical use that are structurally related to
curare Curare ( or ; or ) is a common name for various alkaloid arrow poisons originating from plant extracts. Used as a paralyzing agent by indigenous peoples in Central and South America for hunting and for therapeutic purposes, curare only ...
. Several are depolarizing agents.


Examples

Examples of common anticholinergics: * Antimuscarinic agents **
Antipsychotics Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizo ...
(
clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...
,
quetiapine Quetiapine ( ), sold under the brand name Seroquel among others, is an atypical antipsychotic medication used in the treatment of schizophrenia, bipolar disorder, bipolar depression, and major depressive disorder. Despite being widely prescri ...
) **
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 ...
**
Benztropine Benzatropine ( INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is ...
**
Biperiden Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease, certain drug-induced movement disorders and Tourette Syndrome. It is not recommended for tardive dyskinesias. It is taken by mouth, in ...
**
Chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken orally (by mouth). The medication takes effect within two hour ...
** Certain
SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...
(
Paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...
) **
Dicyclomine Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS). It is taken by mouth or by inje ...
(
Dicycloverine Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS). It is taken by mouth or by injec ...
) **
Dimenhydrinate Dimenhydrinate, also known as diphenhydramine/8-chlorotheophylline salt and sold under the brand names Dramamine and Gravol, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theocl ...
**
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 ...
**
Doxepin Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For label updates seFDA index page for NDA 022036/ref> For hives it ...
**
Doxylamine Doxylamine is an antihistamine medication used to treat insomnia and allergies, and—in combination with pyridoxine ( vitamin B6)—to treat morning sickness in pregnant women. It is available over-the-counter and is sold under such brand names ...
**
Flavoxate Flavoxate is an anticholinergic with antimuscarinic effects. Its muscle relaxant properties may be due to a direct action on the smooth muscle rather than by antagonizing muscarinic receptors. Clinical uses Flavoxate is used to treat urinary bl ...
** Glycopyrronium/-late **
Hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...
**
Ipratropium Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons. The inhalant opens up the medium ...
**
Orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in ...
** Oxitropium **
Oxybutynin Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect ...
**
Promethazine Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold a ...
** Propantheline bromide **
Scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...
**
Solifenacin Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency. Benefits appear simi ...
**
Tolterodine Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth. Common side effects include head ...
**
Tiotropium Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is ...
**
Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...
**
Trihexyphenidyl Trihexyphenidyl (THP, benzhexol, trihex, marketed as Artane and others) is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of P ...
**
Tropicamide Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with the examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effect ...
** Umeclidinium * Antinicotinic agents **
Bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...
– Ganglion blocker **
Dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...
- Cough suppressant and ganglion blocker ** Doxacurium – Nondepolarizing skeletal muscular relaxant **
Hexamethonium Hexamethonium is a non-depolarising ganglionic blocker, a neuronal nicotinic ( nAChR) receptor antagonist that acts in autonomic ganglia by binding mostly in or on the nAChR receptor, and not the acetylcholine binding site itself. It does no ...
– Ganglion blocker **
Mecamylamine Mecamylamine (INN, BAN; or mecamylamine hydrochloride (USAN); brand names Inversine, Vecamyl) is a non-selective, non-competitive antagonist of the nicotinic acetylcholine receptors (nAChRs) that was introduced in the 1950s as an antihypertens ...
– Ganglion blocker and occasional
smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...
aid **
Tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic benzylisoquinoline alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxat ...
- Nondepolarizing skeletal muscular relaxant


Antidotes

Physostigmine Physostigmine (also known as eserine from ''éséré'', the West African name for the Calabar bean) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and ...
is one of only a few drugs that can be used as an antidote for anticholinergic poisoning.
Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
also counteracts anticholinergics by activating
nicotinic acetylcholine receptors 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 ...
.
Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...
(although an
adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...
receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...
) can counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.


Psychoactive uses

When a significant amount of an anticholinergic is taken into the body, a toxic reaction known as acute anticholinergic syndrome may result. This may happen accidentally or intentionally as a consequence of either
recreational Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...
or
entheogen Entheogens are psychoactive substances used in spiritual and religious contexts to induce altered states of consciousness. Hallucinogens such as the psilocybin found in so-called "magic" mushrooms have been used in sacred contexts since ancie ...
ic drug use, though many users find the side effects to be exceedingly unpleasant and not worth the recreational effects they experience. In the context of recreational use, anticholinergics are often called
deliriants Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to t ...
.


Plant sources

The most common plants containing anticholinergic
alkaloids Alkaloids are a broad class of naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large variety of organisms i ...
(including
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 ...
,
scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a medication used to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin a ...
, and
hyoscyamine Hyoscyamine (also known as daturine or duboisine) is a naturally occurring tropane alkaloid and plant toxin. It is a secondary metabolite found in certain plants of the family Solanaceae, including Hyoscyamus niger, henbane, Mandragora officina ...
among others) are: *''
Atropa belladonna ''Atropa bella-donna'', commonly known as deadly nightshade or belladonna, is a toxic perennial herbaceous plant in the nightshade family Solanaceae, which also includes tomatoes, potatoes and eggplant. It is native to Europe and Western Asia, i ...
'' (deadly nightshade) *''
Brugmansia ''Brugmansia'' is a genus of seven species of flowering plants in the nightshade family Solanaceae. They are woody trees or shrubs, with pendulous flowers, and have no spines on their fruit. Their large, fragrant flowers give them their common n ...
'' species *''
Datura ''Datura'' is a genus of nine species of highly poisonous, Vespertine (biology), vespertine-flowering plants belonging to the nightshade family (Solanaceae). They are commonly known as thornapples or jimsonweeds, but are also known as devil's t ...
'' species *''
Garrya ''Garrya'' is a genus of flowering plants in the family Garryaceae native to Mexico, the western United States, Central America and the Greater Antilles. Common names include silk tassel and tassel bush. They are evergreen dioecious wind-pollin ...
'' species *''
Hyoscyamus niger Henbane (''Hyoscyamus niger'', also black henbane and stinking nightshade) is a poisonous plant belonging to tribe Hyoscyameae of the nightshade family ''Solanaceae''. Henbane is native to temperate Europe and Siberia, and naturalised in Great B ...
'' (henbane) *''
Mandragora officinarum ''Mandragora officinarum'' is the type species of the plant genus '' Mandragora'' in the nightshade family Solanaceae. It is often known as mandrake, although this name is also used for other plants. , sources differed significantly in the specie ...
'' (mandrake)


Use as a deterrent

Several narcotic and
opiate An opiate is an alkaloid substance derived from opium (or poppy straw). It differs from the similar term ''opioid'' in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain ( ...
-containing drug preparations, such as those containing
hydrocodone Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically, it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone fo ...
and
codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
are combined with an anticholinergic agent to deter intentional misuse. Examples include hydrocodone/homatropine (Tussigon, Hydromet, Hycodan), diphenoxylate/atropine (Lomotil), and hydrocodone polistirex/chlorpheniramine polistirex (Tussionex Pennkinetic, TussiCaps). However, it is noted that opioid/antihistamine combinations are used clinically for their synergistic effect in the management of pain and maintenance of dissociative
anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...
(sedation) in such preparations as
meperidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Ot ...
/
promethazine Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold a ...
(Mepergan) and
dipipanone Dipipanone, sold under the brand names of Pipadone and Diconal is a strong opioid analgesic drug, used for acute pain by mouth ( PO) for adults. It is often used in instances where morphine is indicated but cannot be used due to the patient being ...
/
cyclizine Cyclizine, sold under a number of brand names, is a medication used to treat and prevent nausea, vomiting and dizziness due to motion sickness or vertigo. It may also be used for nausea after general anaesthesia or that which developed from opio ...
(Diconal), which act as strong anticholinergic agents.


References

{{Authority control Medical mnemonics