Anticholinergic#Side effects

Anticholinergic drugs are used to treat a variety of conditions:

• Dizziness (including vertigo and motion sickness-related symptoms)
• Extrapyramidal symptoms, a potential side-effect of antipsychotic medications
• Gastrointestinal disorders (e.g., peptic ulcers, diarrhea, pylorospasm, diverticulitis, ulcerative colitis, nausea, and vomiting)
• Genitourinary disorders (e.g., cystitis, urethritis, and prostatitis)
• Insomnia, although usually only on a short-term basis
• Respiratory disorders (e.g., asthma, chronic bronchitis, and chronic obstructive pulmonary disease [COPD])
• Sinus bradycardia due to a hypersensitive vagus nerve
• Organophosphate based nerve agent poisoning, such as VX, sarin, tabun, and soman (atropine is favoured in conjunction with an oxime, usually pralidoxime){{Cite web|title=NERVE AGENTS|url=https://fas.org/nuke/guide/usa/doctrine/army/mmcch/NervAgnt.htm#MEDICAL%20MANAGEMENT|access-date=2020-07-27|website=fas.org}}{{Cite journal|last1=Nair|first1=V. Priya|last2=Hunter|first2=Jennifer M.|date=2004-10-01|title=Anticholinesterases and anticholinergic drugs|url=https://academic.oup.com/bjaed/article/4/5/164/291028|journal=Continuing Education in Anaesthesia, Critical Care & Pain|language=en|volume=4|issue=5|pages=164–168|doi=10.1093/bjaceaccp/mkh045|issn=1743-1816|doi-access=free}}

Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.Page 592 in: {{cite book |author1=Cahalan, Michael D. |author2=Barash, Paul G. |author3=Cullen, Bruce F. |author4=Stoelting, Robert K. |title=Clinical Anesthesia |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2009 |isbn=978-0-7817-8763-5 }}{{cite book|url=https://books.google.com/books?id=-YI9P2DLe9UC|title=Clinical Anesthesia|access-date=8 December 2014|url-status=live|archive-url=https://web.archive.org/web/20170220091947/https://books.google.com/books?id=-YI9P2DLe9UC|archive-date=20 February 2017|isbn=9780781787635|last1=Barash|first1=Paul G.|year=2009|publisher=Lippincott Williams & Wilkins }}

Until the beginning of the 20th century, anticholinergic drugs were widely used to treat psychiatric disorders.Bangen, Hans: Geschichte der medikamentösen Therapie der Schizophrenie. Berlin 1992, {{ISBN|3-927408-82-4}}

Effects of anticholinergic drugs include:

• Delirium (often with hallucinations and delusions indistinguishable from reality)
• Ocular symptoms (from eye drops): mydriasis, pupil dilation, and acute angle-closure glaucoma in those with shallow anterior chamber{{cite web | title=ATROPINE- atropine sulfate solution/ drops | website=DailyMed | date=2017-11-20 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7b40bf1-3063-4849-a5a0-0ac5d0d1e72a | access-date=2020-03-28}}{{cite web | title=MYDRIACYL- tropicamide solution/ drops | website=DailyMed | date=2019-12-13 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57165763-29dc-4812-b840-a8a5086416f3 | access-date=2020-03-28}}{{cite web | title=MYDRIACYL- tropicamide solution/ drops | website=DailyMed | date=2019-12-13 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d4f4a2e-eb00-4c65-b3fa-baf5738d468d | access-date=2020-03-28}}
• Anhidrosis, dry mouth, dry skin
• Fever
• Constipation
• Tachycardia
• Urinary retention
• Cutaneous vasodilation

Clinically the most significant feature is delirium, particularly in the elderly, who are most likely to be affected by the toxidrome.

Long-term use may increase the risk of both cognitive and physical decline.{{cite journal |last1=Fox |first1=C |last2=Smith |first2=T |last3=Maidment |first3=I |last4=Chan |first4=WY |last5=Bua |first5=N |last6=Myint |first6=PK |last7=Boustani |first7=M |last8=Kwok |first8=CS |last9=Glover |first9=M |last10=Koopmans|first10=I|last11=Campbell|first11=N|title=Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review |journal=Age and Ageing |date=September 2014 |volume=43 |issue=5|pages=604–15|pmid=25038833|doi=10.1093/ageing/afu096|doi-access=free }}{{cite journal |last1=Andre |first1=L |last2=Gallini |first2=A |last3=Montastruc |first3=F |last4=Montastruc |first4=JL |last5=Piau |first5=A |last6=Lapeyre-Mestre |first6=M |last7=Gardette |first7=V |title=Association between anticholinergic (atropinic) drug exposure and cognitive function in longitudinal studies among individuals over 50 years old: a systematic review. |journal=European Journal of Clinical Pharmacology |date=29 August 2019 |volume=75 |issue=12 |pages=1631–1644 |doi=10.1007/s00228-019-02744-8 |pmid=31468067|s2cid=201675824 }} It is unclear whether they affect the risk of death generally. However, in older adults they do appear to increase the risk of death.{{cite journal |last1=Ruxton|first1=K|last2=Woodman|first2=RJ|last3=Mangoni|first3=AA|title=Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis.|journal=British Journal of Clinical Pharmacology|date=2 March 2015 |pmid=25735839|doi=10.1111/bcp.12617|volume=80|issue=2|pages=209–20|pmc=4541969}}

The anticholinergic burden (ACB) approach examines this risk.{{Cite web|url=https://www.hey.nhs.uk/patient-leaflet/anticholinergic-burden-acb/|title=Anticholinergic Burden (ACB)|date=January 6, 2022}}{{Cite web|url=https://www.acbcalc.com/|title=ACB Calculator|website=www.acbcalc.com}}

Possible effects of anticholinergics include:

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• Poor coordination
• Dementia{{cite journal |last1=Falk |first1=N |last2=Cole |first2=A |last3=Meredith |first3=TJ |title=Evaluation of Suspected Dementia. |journal=American Family Physician |date=15 March 2018 |volume=97 |issue=6 |pages=398–405 |pmid=29671539}}{{cite journal | vauthors = Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB | display-authors = 6 | title = Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | journal = JAMA Internal Medicine | volume = 175 | issue = 3 | pages = 401–407 | date = March 2015 | pmid = 25621434 | pmc = 4358759 | doi = 10.1001/jamainternmed.2014.7663 | author5-link = Rebecca Hubbard }}
• Decreased mucus production in the nose and throat; consequent dry, sore throat
• Dry mouth with possible acceleration of dental caries
• Cessation of sweating; consequent decreased epidermal thermal dissipation leading to warm, blotchy, or red skin
• Increased body temperature
• Pupil dilation; consequent sensitivity to bright light (photophobia)
• Loss of accommodation (loss of focusing ability, blurred vision – cycloplegia)
• Double vision
• Increased heart rate
• Tendency to be easily startled
• Urinary retention
• Urinary incontinence while sleeping
• Diminished bowel movement, sometimes ileus (decreases motility via the vagus nerve)
• Increased intraocular pressure; dangerous for people with narrow-angle glaucoma

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Possible effects in the central nervous system resemble those associated with delirium, and may include:

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• Confusion
• Disorientation
• Agitation
• Euphoria or dysphoria
• Respiratory depression
• Memory problems{{Cite journal|last=Talan|first=Jamie|title=Common Drugs May Cause Cognitive Problems|journal=Neurology Now|date=July–August 2008|volume=4|issue=4|pages=10–11|url=https://www.brainandlife.org/articles/common-drugs-may-cause-cognitive-problems/ |archive-url=https://web.archive.org/web/20190626181238/https://www.brainandlife.org/articles/common-drugs-may-cause-cognitive-problems/ |url-status=dead |archive-date=2019-06-26 |access-date=26 June 2019 |doi=10.1097/01.NNN.0000333835.93556.d1|url-access=subscription}}
• Inability to concentrate
• Wandering thoughts; inability to sustain a train of thought
• Incoherent speech
• Irritability
• Mental confusion (brain fog)
• Wakeful myoclonic jerking
• Unusual sensitivity to sudden sounds
• Illogical thinking
• Photophobia
• Visual disturbances {{Citation needed|date=January 2019}}
• Periodic flashes of light
• Periodic changes in visual field
• Visual snow
• Restricted or "tunnel vision"
• Visual, auditory, or other sensory hallucinations
• Warping or waving of surfaces and edges
• Textured surfaces
• "Dancing" lines; "spiders", insects; form constants
• Lifelike objects indistinguishable from reality
• Phantom smoking
• Hallucinated presence of people not actually there (e.g. shadow people)
• Rarely: seizures, coma, and death
• Orthostatic hypotension (severe drop in systolic blood pressure when standing up suddenly) and significantly increased risk of falls in the elderly population{{cite web|url=http://lifeline.theonlinelearningcenter.com/SCOframe.aspx|archive-url=https://archive.today/20120712173900/http://lifeline.theonlinelearningcenter.com/SCOframe.aspx|url-status=dead|archive-date=12 July 2012|title=Lifeline Learning Center|publisher=Lifeline.theonlinelearningcenter.com|access-date=8 December 2014}}

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Older patients are at a higher risk of experiencing CNS side effects.{{Citation needed|date=December 2023}} 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.{{Cite journal |last1=Taylor-Rowan |first1=Martin |last2=Alharthi |first2=Ahmed A. |last3=Noel-Storr |first3=Anna H. |last4=Myint |first4=Phyo K. |last5=Stewart |first5=Carrie |last6=McCleery |first6=Jenny |last7=Quinn |first7=Terry J. |date=2023-12-08 |title=Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=12 |pages=CD015405 |doi=10.1002/14651858.CD015405.pub2 |issn=1469-493X |pmc=10704558 |pmid=38063254}}

An acute anticholinergic syndrome is reversible and subsides once all of the causative agents have been excreted. Reversible acetylcholinesterase inhibitor agents such as physostigmine 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.Rosen, Peter, John A. Marx, Robert S. Hockberger, and Ron M. Walls. Rosen's Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia, PA: Mosby Elsevier, 2014.

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.{{Citation needed|date=March 2025|reason=The editor reported the findings of a study published in what I presume is a journal.}} However, in a March 2025 article published in the American Journal of Epidemiology, Aguado and colleagues{{Cite journal |last=Aguado |first=Jaume |last2=Gutierrez |first2=Lia |last3=Forns |first3=Joan |last4=Vila-Guilera |first4=Julia |last5=Rothman |first5=Kenneth J |last6=García-Albéniz |first6=Xabier |date=2025-03-04 |title=Effect of different durations of treatment with antihypertensive drugs with anticholinergic effects on the risk of dementia: a target trial emulation study |url=https://academic.oup.com/aje/article/194/3/691/7728136 |journal=American Journal of Epidemiology |language=en |volume=194 |issue=3 |pages=691–698 |doi=10.1093/aje/kwae263 |issn=0002-9262|url-access=subscription }} reported that anticholinergic antihypertensive medications reduced individuals' 10-year risk of incident vascular dementia by 31% when used for ≥6 years compared to 3–6 years (risk ratio, 0.69; 95% CI, 0.54–0.90); the comparative risk of Alzheimer's disease was reduced, as well, but not to a statistically significant degree (risk ratio, 0.91; 95% CI, 0.77–1.10).{{cn|date=March 2025}}

Anticholinergics are classified according to the receptors that are affected:

• Antimuscarinic agents operate on the muscarinic acetylcholine receptors. The majority of anticholinergic drugs are antimuscarinics.
• Antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of these are non-depolarising skeletal muscle relaxants for surgical use that are structurally related to curare. Several are depolarizing agents.

Examples of common anticholinergics:

{{div col|colwidth=20em}}

• Antimuscarinic agents
• Antipsychotics (clozapine, quetiapine){{cite web |title=[113] How well do you know your anticholinergic (antimuscarinic) drugs? {{!}} Therapeutics Initiative |url=https://www.ti.ubc.ca/2018/09/10/113-anticholinergic-antimuscarinic-drugs/ |website=Therapeutics Initiative |access-date=20 September 2018 |date=10 September 2018}}
• Atropine
• Benztropine
• Biperiden
• Chlorpheniramine
• Certain SSRIs (Paroxetine)
• Dicyclomine (Dicycloverine)
• Dimenhydrinate
• Diphenhydramine
• Doxepin
• Doxylamine
• Flavoxate
• Glycopyrronium/-late
• Hyoscyamine
• Ipratropium
• Orphenadrine
• Oxitropium
• Oxybutynin
• Promethazine
• Propantheline bromide
• Scopolamine
• Solifenacin
• Tolterodine
• Tiotropium
• Tricyclic antidepressants
• Trihexyphenidyl
• Tropicamide
• Umeclidinium
• Antinicotinic agents
• Bupropion – Ganglion blocker{{cite book |vauthors=Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI |chapter=Bupropion and Bupropion Analogs as Treatments for CNS Disorders |title=Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse |volume=69 |pages=177–216 |year=2014 |pmid=24484978 |doi=10.1016/B978-0-12-420118-7.00005-6 |series=Advances in Pharmacology |isbn=9780124201187 }}{{cite book | author = Dwoskin, Linda P. | title = Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse | url = https://books.google.com/books?id=b3UpAgAAQBAJ&pg=PA177 | date = 29 January 2014 | publisher = Elsevier Science | isbn = 978-0-12-420177-4 | pages = 177–216 | url-status = live | archive-url = https://web.archive.org/web/20170320155042/https://books.google.com/books?id=b3UpAgAAQBAJ&pg=PA177 | archive-date = 20 March 2017 }}{{cite book | author1 = Tasman, Allan | author2 = Kay, Jerald | author3 = Lieberman, Jeffrey A. | author4 = First, Michael B. | author5 = Maj, Mario | title = Psychiatry | url = https://books.google.com/books?id=vVG7zz7eaxcC&pg=RA9-PT2900 | date = 11 October 2011 | publisher = John Wiley & Sons | isbn = 978-1-119-96540-4 | url-status = live | archive-url = https://web.archive.org/web/20170320140656/https://books.google.com/books?id=vVG7zz7eaxcC&pg=RA9-PT2900 | archive-date = 20 March 2017 }}
• Dextromethorphan - Cough suppressant and ganglion blocker{{cite journal |doi=10.1124/jpet.104.075093 |pmid=15356218 |title=Effect of Dextrometorphan and Dextrorphan on Nicotine and Neuronal Nicotinic Receptors: In Vitro and in Vivo Selectivity |journal=Journal of Pharmacology and Experimental Therapeutics |volume=312 |issue=2 |pages=780–5 |year=2004 |last1=Damaj |first1=M. I. |last2=Flood |first2=P |last3=Ho |first3=K. K. |last4=May |first4=E. L. |last5=Martin |first5=B. R. |s2cid=149958 }}{{cite journal |doi=10.1016/j.ejphar.2006.02.034 |pmid=16563374 |title=Effects of dextrorotatory morphinans on α3β4 nicotinic acetylcholine receptors expressed in Xenopus oocytes |journal=European Journal of Pharmacology |volume=536 |issue=1–2 |pages=85–92 |year=2006 |last1=Lee |first1=Jun-Ho |last2=Shin |first2=Eun-Joo |last3=Jeong |first3=Sang Min |last4=Kim |first4=Jong-Hoon |last5=Lee |first5=Byung-Hwan |last6=Yoon |first6=In-Soo |last7=Lee |first7=Joon-Hee |last8=Choi |first8=Sun-Hye |last9=Lee |first9=Sang-Mok |last10=Lee |first10=Phil Ho |last11=Kim |first11=Hyoung-Chun |last12=Nah |first12=Seung-Yeol }}{{cite journal |pmid=10869398 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10869398 |year=2000 |last1=Hernandez |first1=S. C. |title=Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=293 |issue=3 |pages=962–7 |last2=Bertolino |first2=M |last3=Xiao |first3=Y |last4=Pringle |first4=K. E. |last5=Caruso |first5=F. S. |last6=Kellar |first6=K. J. }}
• Doxacurium – Nondepolarizing skeletal muscular relaxant
• Hexamethonium – Ganglion blocker
• Mecamylamine – Ganglion blocker and occasional smoking cessation aid{{cite journal|last=Shytle|first=RD|author2=Penny, E |author3=Silver, AA |author4=Goldman, J |author5= Sanberg, PR |title=Mecamylamine (Inversine): an old antihypertensive with new research directions |journal=Journal of Human Hypertension|date=Jul 2002|volume=16|issue=7|pages=453–7|pmid=12080428 |doi=10.1038/sj.jhh.1001416|doi-access=free}}
• Tubocurarine - Nondepolarizing skeletal muscular relaxant

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Physostigmine is one of only a few drugs that can be used as an antidote for anticholinergic poisoning. Nicotine also counteracts anticholinergics by activating nicotinic acetylcholine receptors. Caffeine (although an adenosine receptor antagonist) can counteract the anticholinergic symptoms by reducing sedation and increasing acetylcholine activity, thereby causing alertness and arousal.

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 or entheogenic 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.{{Cite journal | doi = 10.1016/j.genhosppsych.2013.04.013| pmid = 23706777| title = Drops of madness? Recreational misuse of tropicamide collyrium; early warning alerts from Russia and Italy| journal = General Hospital Psychiatry| volume = 35| issue = 5| pages = 571–3| year = 2013| last1 = Bersani | first1 = F. S. | last2 = Corazza | first2 = O. | last3 = Simonato | first3 = P. | last4 = Mylokosta | first4 = A. | last5 = Levari | first5 = E. | last6 = Lovaste | first6 = R. | last7 = Schifano | first7 = F. }}

The most common plants containing anticholinergic alkaloids (including atropine, scopolamine, and hyoscyamine among others) are:

• Atropa belladonna (deadly nightshade)
• Brugmansia species
• Datura species
• Garrya species
• Hyoscyamus niger (henbane)
• Mandragora officinarum (mandrake)

Several narcotic and opiate-containing drug preparations, such as those containing hydrocodone and codeine are combined with an anticholinergic agent to deter intentional misuse.{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=5209&type=display|title=NIH DailyMed – Hydromet Syrup|publisher=Dailymed.nlm.nih.gov|access-date=2008-08-17|url-status=live|archive-url=https://web.archive.org/web/20110523224811/http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=5209&type=display|archive-date=2011-05-23}} 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 (sedation) in such preparations as meperidine/promethazine (Mepergan) and dipipanone/cyclizine (Diconal), which act as strong anticholinergic agents.{{cite journal|title=Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers|doi=10.1007/s00213-002-1245-5|pmid=12404072|volume=165|issue=2|journal=Psychopharmacology|pages=146–156|year = 2003|last1 = Zacny|first1 = James P.|s2cid=7835794}}

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