Anticholinergic
Encyclopedia
An anticholinergic agent is a substance that blocks the neurotransmitter
acetylcholine
in the central
and the peripheral nervous system
. An example of an anticholinergic is dicycloverine, and the classic example is atropine
.
Anticholinergics are administered to reduce the effects mediated by acetylcholine on acetylcholine receptors in neuron
s through competitive inhibition. Therefore, their effects are reversible.
Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fiber
s of the parasympathetic system are responsible for the involuntary movement
s of smooth muscles present in the gastrointestinal tract
, urinary tract, lungs, etc. Anticholinergics are divided into three categories in accordance with their specific targets in the central and/or peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers
.
Examples of anticholinergics:
Physostigmine
is one of a few drugs that are used as antidotes for anticholinergic poisoning. Nicotine
also counteracts anticholinergics.
Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most have at least some sedative effect, both being advantageous in surgical procedures.
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 recreational drug use
. Anticholinergic drugs are usually considered the least enjoyable by experienced recreational drug users, possibly due to the lack of euphoria caused by them. In terms of recreational use, these drugs are commonly referred to as deliriant
s. Because most users do not enjoy the experience, they do not use it again, or do so very rarely. The risk of addiction is low in the anticholinergic class. The effects are usually more pronounced in the elderly, due to natural reduction of acetylcholine production associated with age.
Exceptions to the above include scopolamine
, orphenadrine
, dicycloverine/dicyclomine
and first-generation antihistamine
s with central nervous system penetration.
Possible effects of anticholinergics include:
Possible effects in the central nervous system
resemble those associated with delirium
, and may include:
agents such as physostigmine
were used but this was found to increase the risk of cardiac toxicity. The current recommended treatment is symptomatic and supportive management.
Piracetam
, Alpha-GPC
and Choline
(and other racetams) are known to activate cholinergic system and alleviate cognitive symptoms caused by extended use of anticholinergic drugs.
, are mixed with an anticholinergic agent to deter intentional overdose.
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
in the central
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
. An example of an anticholinergic is dicycloverine, and the classic example is atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
.
Anticholinergics are administered to reduce the effects mediated by acetylcholine on acetylcholine receptors in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s through competitive inhibition. Therefore, their effects are reversible.
Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fiber
Nerve fiber
A nerve fiber is a threadlike extension of a nerve cell and consists of an axon and myelin sheath in the nervous system. There are nerve fibers in the central nervous system and peripheral nervous system. A nerve fiber may be myelinated and/or unmyelinated. In the central nervous system , myelin...
s of the parasympathetic system are responsible for the involuntary movement
Movement disorder
Movement disorders include:* Akathisia * Akinesia * Associated Movements * Athetosis...
s of smooth muscles present in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, urinary tract, lungs, etc. Anticholinergics are divided into three categories in accordance with their specific targets in the central and/or peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers
Neuromuscular-blocking drug
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...
.
Pharmacology
Anticholinergics are classified according to the receptors that are affected:- Antimuscarinic agents operate on the muscarinic acetylcholine receptorMuscarinic acetylcholine receptorMuscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s. The majority of anticholinergic drugs are antimuscarinics. - Antinicotinic agents operate on the nicotinic acetylcholine receptorNicotinic acetylcholine receptorNicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
s. The majority of these are non-depolarising skeletal muscleSkeletal muscleSkeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
relaxants for surgical use, along with a few of the depolarising agents and drugs of other categories structurally related to curareCurareCurare is a common name for various arrow poisons originating from South America. The three main types of curare are:* tubocurare...
.
Examples of anticholinergics:
- ipratropium bromideIpratropiumIpratropium bromide is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi...
(Atrovent) - oxitropium bromide (Oxivent)
- tiotropiumTiotropiumTiotropium bromide is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease . Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheim and Pfizer under the trade name Spiriva...
(Spiriva) - Glycopyrrolate (Robinul)
- oxybutinin (Ditropan, Lyrinel XL)
- TolterodineTolterodineTolterodine is an antimuscarinic drug that is used to treat urinary incontinence.It is marketed by Pfizer in Canada and the United States by its brand name Detrol. In Egypt it is also found under the trade names Tolterodine by Sabaa and Incont L.A...
(Detrol)
Physostigmine
Physostigmine
Physostigmine is a parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean....
is one of a few drugs that are used as antidotes for anticholinergic poisoning. Nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
also counteracts anticholinergics.
Effects
Anticholinergic drugs are used in treating a variety of conditions:- Gastrointestinal disorders (e.g., gastritisGastritisGastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...
, pylorospasm, diverticulitisDiverticulitisDiverticulitis is a common digestive disease particularly found in the large intestine. Diverticulitis develops from diverticulosis, which involves the formation of pouches on the outside of the colon...
, ulcerative colitisUlcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
) - Genitourinary disorders (e.g., cystitisCystitisCystitis is a term that refers to urinary bladder inflammation that results from any one of a number of distinct syndromes. It is most commonly caused by a bacterial infection in which case it is referred to as a urinary tract infection.-Signs and symptoms:...
, urethritisUrethritisUrethritis is inflammation of the urethra. The most common symptom is painful or difficult urination.-Causes:The disease is classified as either gonococcal urethritis, caused by Neisseria gonorrhoeae, or non-gonococcal urethritis , most commonly caused by Chlamydia trachomatis...
, prostatitisProstatitisProstatitis is an inflammation of the prostate gland, in men. A prostatitis diagnosis is assigned at 8% of all urologist and 1% of all primary care physician visits in the United States.-Classification:...
) - Respiratory disorders (e.g., asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, chronic bronchitisChronic bronchitisChronic bronchitis is a chronic inflammation of the bronchi in the lungs. It is generally considered one of the two forms of chronic obstructive pulmonary disease...
) - Sinus bradycardiaSinus bradycardiaSinus bradycardia is a heart rhythm that originates from the sinus node and has a rate of under 60 beats per minute.-Signs and symptoms:The decreased heart rate can cause a decreased cardiac output resulting in symptoms such as lightheadedness, dizziness, hypotension, vertigo, and syncope...
- Hypersensitive vagus nerveVagus nerveThe vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves... - InsomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, though usually only on a short term basis.
Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most have at least some sedative effect, both being advantageous in surgical procedures.
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 recreational drug use
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...
. Anticholinergic drugs are usually considered the least enjoyable by experienced recreational drug users, possibly due to the lack of euphoria caused by them. In terms of recreational use, these drugs are commonly referred to as deliriant
Deliriant
The deliriants are a special class of acetylcholine-inhibitor hallucinogen. The term was introduced by David F. Duncan and Robert S...
s. Because most users do not enjoy the experience, they do not use it again, or do so very rarely. The risk of addiction is low in the anticholinergic class. The effects are usually more pronounced in the elderly, due to natural reduction of acetylcholine production associated with age.
Exceptions to the above include scopolamine
Scopolamine
Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...
, orphenadrine
Orphenadrine
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class with prominent CNS and peripheral actions used to treat painful muscle spasms, other similar conditions, as well as the treatment...
, dicycloverine/dicyclomine
Dicyclomine
Dicyclomine, also known as dicycloverine, is an anticholinergic that blocks muscarinic receptors. Dicycloverine was first synthesized in the United States circa 1947.- Clinical uses :...
and first-generation antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
s with central nervous system penetration.
Possible effects of anticholinergics include:
- AtaxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
; loss of coordination - Decreased mucus production in the nose and throatThroatIn vertebrate anatomy, the throat is the anterior part of the neck, in front of the vertebral column. It consists of the pharynx and larynx...
; consequent dry, sore throat - XerostomiaXerostomiaXerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
or dry-mouth with possible acceleration of dental cariesDental cariesDental caries, also known as tooth decay or a cavity, is an irreversible infection usually bacterial in origin that causes demineralization of the hard tissues and destruction of the organic matter of the tooth, usually by production of acid by hydrolysis of the food debris accumulated on the... - Cessation of perspiration; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin
- Increased body temperature
- Pupil dilation (mydriasisMydriasisMydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
); consequent sensitivity to bright light (photophobiaPhotophobiaPhotophobia is a 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 of actual physical photosensitivity of the eyes, though the term...
) - Loss of accommodation (loss of focusing ability, blurred vision — cycloplegiaCycloplegiaCycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...
) - Double-vision (diplopiaDiplopiaDiplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
) - Increased heart rate (tachycardiaTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
) - Tendency to be easily startled
- Urinary retentionUrinary retentionUrinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
- Diminished bowel movement, sometimes ileusIleusIleus is a disruption of the normal propulsive ability of the gastrointestinal tract.Ileus is commonly defined simply as bowel obstruction. However, authoritative sources define it as decreased motor activity of the GI tract due to non-mechanical causes...
- (decreases motility via the vagus nerveVagus nerveThe vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
) - Increased intraocular pressureIntraocular pressureIntraocular pressure 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 from glaucoma...
; dangerous for people with narrow-angle glaucomaGlaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye... - Shaking
Possible effects in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
resemble those associated with delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, and may include:
- Confusion
- Disorientation
- Agitation
- EuphoriaEuphoriaEuphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
or dysphoriaDysphoriaDysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in... - Respiratory depression
- Memory problems
- Inability to concentrate
- Wandering thoughts; inability to sustain a train of thoughtTrain of thoughtThe train of thought, stream of thought, trail of thought, or chain 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 another.When a...
- Incoherent speech
- Wakeful myoclonic jerking
- Unusual sensitivity to sudden sounds
- Illogical thinking
- Photophobia
- Visual disturbances
- Periodic flashes of light
- Periodic changes in visual field
- Visual snowVisual snowVisual snow is a transitory or persisting visual symptom where people see snow or television-like static in parts or the whole of their visual fields, especially against dark backgrounds...
- Restricted or "tunnel vision"
- Visual, auditory, or other sensory hallucinationHallucinationA hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s- Warping or waving of surfaces and edges
- Textured surfaces
- "Dancing" lines; "spiders", insects; form constants
- Lifelike objects indistinguishable from reality
- Hallucinated presence of people not actually there
- Rarely: seizures, coma, and death
- Orthostatic hypotention (sudden dropping of systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population.
Remedies
Acute anticholinergic syndrome is completely reversible and subsides once all of the toxin has been excreted. Previously, reversible cholinergicCholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...
agents such as physostigmine
Physostigmine
Physostigmine is a parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean....
were used but this was found to increase the risk of cardiac toxicity. The current recommended treatment is symptomatic and supportive management.
Piracetam
Piracetam
Piracetam is a nootropic drug. Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid . Piracetam is a cyclic derivative of GABA. It is one of the group of racetams...
, Alpha-GPC
Alpha-GPC
L-Alpha Glycerylphosphorylcholine is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and is used as a nootropic dietary supplement to enhance memory and...
and Choline
Choline
Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....
(and other racetams) are known to activate cholinergic system and alleviate cognitive symptoms caused by extended use of anticholinergic drugs.
Plant sources
The most common plants containing anticholinergic alkaloids are:- Atropa belladonna (Deadly Nightshade)
- BrugmansiaBrugmansiaBrugmansia is a genus of seven species of flowering plants in the family Solanaceae, native to subtropical regions of South America, along the Andes from Colombia to northern Chile, and also in southeastern Brazil. They are known as Angel's Trumpets, sharing that name with the closely related genus...
species (Brugmansia) - DaturaDaturaDatura is a genus of nine species of vespertine flowering plants belonging to the family Solanaceae. Its precise and natural distribution is uncertain, owing to its extensive cultivation and naturalization throughout the temperate and tropical regions of the globe...
species (Datura) - Hyoscamus nigerHenbaneHenbane , also known as stinking nightshade or black henbane, is a plant of the family Solanaceae that originated in Eurasia, though it is now globally distributed.-Toxicity and historical usage:...
(Henbane) - Mandragora officinarumMandrake (plant)Mandrake is the common name for members of the plant genus Mandragora, particularly the species Mandragora officinarum, belonging to the nightshades family...
(Mandrake).
Use as a deterrent
Certain preparations of some drugs, such as hydrocodoneHydrocodone
Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from either of two naturally occurring opiates: codeine and thebaine. It is an orally active narcotic analgesic and antitussive...
, are mixed with an anticholinergic agent to deter intentional overdose.