Anticholinergic

Anticholinergic (anticholinergic agent) is a group of substances that blocks the action of the neurotransmitter acetylcholine (ACh) at synapses in the central and the peripheral nervous system, and, in broad terms, neuromuscular junction.[1][2]

These agents inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body;[3] cholinergic process otherwise by enhancing ACh function.[3]

In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central, peripheral nervous system and neuromuscular junction:[3] antimuscarinic agents, and antinicotinic agents (ganglionic blockers, neuromuscular blockers).[4]

In strict terms, anticholinergic only comprises antimuscarinic which competitively inhibits binding of the neurotransmitter acetylcholine to muscarinic acetylcholine receptors though.[3][5]; anticholinergic agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, for example.[5][3] (See: Cholinergic crisis § treatment and Cholinesterase inhibitor)

Medical usesEdit

Anticholinergic drugs are used to treat a variety of conditions:

Anticholinergics generally have antisialagogue effects (decreasing saliva production), and most produce some level of sedation, both being advantageous in surgical procedures.[6][7]

Until the beginning of the 20th century anticholinergic drugs were used widely in psychiatric disorders.[8]

Physiological effectsEdit

[3]

Clinically the most significant feature is delirium, particularly in the elderly, who are most likely to be affected by the toxidrome.[3]

Side effectsEdit

Long-term use may increase the risk of both cognitive and physical decline.[12][13] It is unclear whether they affect the risk of death generally.[12] However, in older adults they do appear to increase the risk of death.[14]

Possible effects of anticholinergics include:

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

  • Confusion
  • Disorientation
  • Agitation
  • Euphoria or dysphoria
  • Respiratory depression
  • Memory problems[16]
  • 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
  • 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
  • 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.[17]

Older patients are at a higher risk of experiencing CNS side effects.

ToxicityEdit

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.[18]

PharmacologyEdit

Anticholinergics are classified according to the receptors that are affected:

ExamplesEdit

Examples of common anticholinergics:

Plants of the family Solanaceae contain various anticholinergic tropane alkaloids, such as scopolamine, atropine, and hyoscyamine.

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.

Recreational usesEdit

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 many recreational drug users. In the context of recreational use, anticholinergics are often called deliriants.[20]

Plant sourcesEdit

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

Use as a deterrentEdit

Several narcotic and opiate-containing drug preparations, such as those containing hydrocodone and codeine are combined with an anticholinergic agent to deter intentional misuse.[28] Examples include Hydromet/Hycodan (hydrocodone/homatropine), Lomotil (diphenoxylate/atropine) and Tussionex (hydrocodone polistirex/chlorpheniramine). 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 Meprozine (meperidine/promethazine) and Diconal (dipipanone/cyclizine), which act as strong anticholinergic agents.[29]

ReferencesEdit

  1. ^ Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2009. Drugs with Anticholinergic Activity. Prescriber's Letter 2011; 18 (12):271233.
  2. ^ "Anticholinergics", Anticholinergic Agents, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31643610, retrieved 2020-03-23, Anticholinergics have antisecretory activities and decrease nasal and bronchial secretions, salivation, lacrimation, sweating and gastric acid production, and can be used to decrease secretions in allergic and inflammatory diseases. Anticholinergics relax smooth muscle in the gastrointestinal tract, bladder and lung and can be used for gastrointestinal, urological or respiratory conditions associated with spasm and dysmotility.
  3. ^ a b c d e f g Migirov, A; Datta, AR (2020), "article-17683", Physiology, Anticholinergic Reaction, This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license, and any changes made are indicated., Treasure Island (FL): StatPearls Publishing, PMID 31536197, retrieved 2020-03-24
  4. ^ Sharee A. Wiggins; Tomas Griebling. "Urinary Incontinence". Landon Center on Aging. Archived from the original on 2011-09-27. Retrieved 2011-07-09. Cite journal requires |journal= (help)
  5. ^ a b Authors: Mark Su, MD, MPH. Matthew Goldman, MD ; Section Editors: Stephen J Traub, MD. Michele M Burns, MD, MPH ;Deputy Editor:Jonathan Grayzel, MD, FAAEM. "Anticholinergic poisoning". UpToDate. Retrieved 2020-03-24.CS1 maint: uses authors parameter (link)
  6. ^ Page 592 in: Cahalan, Michael D.; Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K. (2009). Clinical Anesthesia. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-8763-5.
  7. ^ Barash, Paul G. (2009). Clinical Anesthesia. ISBN 9780781787635. Archived from the original on 20 February 2017. Retrieved 8 December 2014.
  8. ^ Bangen, Hans: Geschichte der medikamentösen Therapie der Schizophrenie. Berlin 1992, ISBN 3-927408-82-4
  9. ^ "ATROPINE- atropine sulfate solution/ drops". DailyMed. 2017-11-20. Retrieved 2020-03-28.
  10. ^ "MYDRIACYL- tropicamide solution/ drops". DailyMed. 2019-12-13. Retrieved 2020-03-28.
  11. ^ "MYDRIACYL- tropicamide solution/ drops". DailyMed. 2019-12-13. Retrieved 2020-03-28.
  12. ^ a b Fox, C; Smith, T; Maidment, I; Chan, WY; Bua, N; Myint, PK; Boustani, M; Kwok, CS; Glover, M; Koopmans, I; Campbell, N (September 2014). "Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review". Age and Ageing. 43 (5): 604–15. doi:10.1093/ageing/afu096. PMID 25038833.
  13. ^ Andre, L; Gallini, A; Montastruc, F; Montastruc, JL; Piau, A; Lapeyre-Mestre, M; Gardette, V (29 August 2019). "Association between anticholinergic (atropinic) drug exposure and cognitive function in longitudinal studies among individuals over 50 years old: a systematic review". European Journal of Clinical Pharmacology. 75 (12): 1631–1644. doi:10.1007/s00228-019-02744-8. PMID 31468067.
  14. ^ Ruxton, K; Woodman, RJ; Mangoni, AA (2 March 2015). "Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis". British Journal of Clinical Pharmacology. 80 (2): 209–20. doi:10.1111/bcp.12617. PMC 4541969. PMID 25735839.
  15. ^ Falk, N; Cole, A; Meredith, TJ (15 March 2018). "Evaluation of Suspected Dementia". American Family Physician. 97 (6): 398–405. PMID 29671539.
  16. ^ Talan, Jamie (July–August 2008). "Common Drugs May Cause Cognitive Problems". Neurology Now. 4 (4): 10–11. doi:10.1097/01.NNN.0000333835.93556.d1. Archived from the original on 2019-06-26. Retrieved 26 June 2019.
  17. ^ "Lifeline Learning Center". Lifeline.theonlinelearningcenter.com. Archived from the original on 12 July 2012. Retrieved 8 December 2014.
  18. ^ 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.
  19. ^ a b c d e "[113] How well do you know your anticholinergic (antimuscarinic) drugs? | Therapeutics Initiative". Therapeutics Initiative. 10 September 2018. Retrieved 20 September 2018.
  20. ^ a b Bersani, F. S.; Corazza, O.; Simonato, P.; Mylokosta, A.; Levari, E.; Lovaste, R.; Schifano, F. (2013). "Drops of madness? Recreational misuse of tropicamide collyrium; early warning alerts from Russia and Italy". General Hospital Psychiatry. 35 (5): 571–3. doi:10.1016/j.genhosppsych.2013.04.013. PMID 23706777.
  21. ^ Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI (2014). Bupropion and bupropion analogs as treatments for CNS disorders. Adv. Pharmacol. Advances in Pharmacology. 69. pp. 177–216. doi:10.1016/B978-0-12-420118-7.00005-6. ISBN 9780124201187. PMID 24484978.
  22. ^ Dwoskin, Linda P. (29 January 2014). Emerging Targets & Therapeutics in the Treatment of Psychostimulant Abuse. Elsevier Science. pp. 177–216. ISBN 978-0-12-420177-4. Archived from the original on 20 March 2017.
  23. ^ Tasman, Allan, Kay, Jerald, Lieberman, Jeffrey A., First, Michael B., Maj, Mario (11 October 2011). Psychiatry. John Wiley & Sons. ISBN 978-1-119-96540-4. Archived from the original on 20 March 2017.
  24. ^ Damaj, M. I.; Flood, P; Ho, K. K.; May, E. L.; Martin, B. R. (2004). "Effect of Dextrometorphan and Dextrorphan on Nicotine and Neuronal Nicotinic Receptors: In Vitro and in Vivo Selectivity". Journal of Pharmacology and Experimental Therapeutics. 312 (2): 780–5. doi:10.1124/jpet.104.075093. PMID 15356218.
  25. ^ Lee, Jun-Ho; Shin, Eun-Joo; Jeong, Sang Min; Kim, Jong-Hoon; Lee, Byung-Hwan; Yoon, In-Soo; Lee, Joon-Hee; Choi, Sun-Hye; Lee, Sang-Mok; Lee, Phil Ho; Kim, Hyoung-Chun; Nah, Seung-Yeol (2006). "Effects of dextrorotatory morphinans on α3β4 nicotinic acetylcholine receptors expressed in Xenopus oocytes". European Journal of Pharmacology. 536 (1–2): 85–92. doi:10.1016/j.ejphar.2006.02.034. PMID 16563374.
  26. ^ Hernandez, S. C.; Bertolino, M; Xiao, Y; Pringle, K. E.; Caruso, F. S.; Kellar, K. J. (2000). "Dextromethorphan and Its Metabolite Dextrorphan Block α3β4 Neuronal Nicotinic Receptors". The Journal of Pharmacology and Experimental Therapeutics. 293 (3): 962–7. PMID 10869398.
  27. ^ Shytle, RD; Penny, E; Silver, AA; Goldman, J; Sanberg, PR (Jul 2002). "Mecamylamine (Inversine): an old antihypertensive with new research directions". Journal of Human Hypertension. 16 (7): 453–7. doi:10.1038/sj.jhh.1001416. PMID 12080428.
  28. ^ "NIH DailyMed – Hydromet Syrup". Dailymed.nlm.nih.gov. Archived from the original on 2011-05-23. Retrieved 2008-08-17.
  29. ^ Zacny, James P. (2003). "Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers". Psychopharmacology. 165 (2): 146–156. doi:10.1007/s00213-002-1245-5. PMID 12404072.