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Toxicity, Anticholinergic

Author: John J Bruns, Jr, MD, Clinical Assistant Professor, Department of Emergency Medicine, Mount Sinai School of Medicine
Contributor Information and Disclosures

Updated: Mar 26, 2008

Introduction

Background

Anticholinergic syndrome (ACS) is produced by the inhibition of cholinergic neurotransmission at muscarinic receptor sites.

For a related CME activity, see CME - New Risk Score Predicts Risk for Anticholinergic Adverse Effects. 

Pathophysiology

Substances with anticholinergic properties competitively antagonize acetylcholine muscarinic receptors; this predominantly occurs at peripheral (eg, heart, salivary glands, sweat glands, GI tract, GU tract) postganglionic parasympathetic muscarinic receptors. Anticholinergic substances minimally compete with acetylcholine at other sites (eg, autonomic ganglia).

Central nervous system (CNS) manifestations result from central cortical and subcortical muscarinic receptor antagonism. The degree of CNS manifestation is related to the drug's ability to cross the blood-brain barrier.

Frequency

United States

Anticholinergic syndrome may be caused by intentional overdose, inadvertent ingestion, medical noncompliance, and geriatric polypharmacy. Systemic effects also have resulted from topical eye drops. Anticholinergic syndrome commonly follows the ingestion of a wide variety of prescription and over-the-counter medications.

Intentional abuse with hallucinogenic plants (eg, Datura stramonium [jimson weed]) and mushrooms (eg, Amanita muscaria) can cause anticholinergic syndrome due to the presence of anticholinergic tropane alkaloids. Scopolamine has been used in beverages as "knockout drops," and several cases of anticholinergic syndrome have been reported following Chinese herbal tea consumption.

According to the American Association of Poison Control Centers, almost 2.4 million cases of human poison exposure were reported to 65 US poison control centers in 2003.1

In 2003, the Toxic Exposure Surveillance System reported 3094 symptomatic anticholinergic drug presentations with unintentional ingestions in 52%, intentional ingestions in 38%, and adverse reactions occurring in 7% of cases; moderate morbidity (requiring specific treatment) was reported in 20%, major morbidity (life-threatening) in 3.7%, and death in 5 cases (case-fatality proportion = 0.16%).1

In 2003, the Toxic Exposure Surveillance System reported 70,251 symptomatic antihistamine presentations with 28,092 specific to diphenhydramine. A total of 64 deaths were attributed to antihistamine toxicity of which 38 were specifically diphenhydramine related for case-fatality proportions of 0.09% and 0.14%, respectively.1

Patients with severe central manifestations (eg, hallucinations, psychoses, seizures, coma) have the highest morbidity rates.

Clinical

History

  • For all patients with suspected poisoning, determine the precise substance(s) ingested, time of ingestion, quantity ingested, rationale for ingestion, and co-ingestants.
  • Ascertain patient compliance, medical history, prescription medications, and nonprescription medications (including natural or herbal products).
  • Many medications have anticholinergic properties, which can result in additive toxicity.
  • Always inquire about use of dermally applied drugs (ie, scopolamine transdermal delivery system).

Physical

  • Anticholinergic syndrome results from the inhibition of muscarinic cholinergic neurotransmission.
  • Clinical manifestations are caused by CNS effects, peripheral nervous system effects, or both.
  • Remember common signs and symptoms with the mnemonic, "red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare." The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status (AMS), and fever, respectively.
  • Additional manifestations include sinus tachycardia, decreased bowel sounds, functional ileus, urinary retention, hypertension, tremulousness, and myoclonic jerking.
  • Patients with central anticholinergic syndrome may present with ataxia, disorientation, short-term memory loss, confusion, hallucinations (visual, auditory), psychosis, agitated delirium, seizures (rare), coma, respiratory failure, and cardiovascular collapse.

Causes

Agents with anticholinergic properties are as follows:

  • Anticholinergics
    • Atropine, scopolamine
    • Glycopyrrolate
    • Benztropine, trihexyphenidyl
  • Antihistamines
    • Chlorpheniramine
    • Cyproheptadine
    • Doxylamine
    • Hydroxyzine
    • Dimenhydrinate
    • Diphenhydramine
    • Meclizine
    • Promethazine
  • Antipsychotics
    • Chlorpromazine
    • Clozapine
    • Mesoridazine
    • Olanzapine
    • Quetiapine
    • Thioridazine
  • Antispasmodics
    • Clidinium
    • Dicyclomine
    • Hyoscyamine
    • Oxybutynin
    • Propantheline
  • Cyclic antidepressants
    • Amitriptyline
    • Amoxapine
    • Clomipramine
    • Desipramine
    • Doxepin
    • Imipramine
    • Nortriptyline
    • Protriptyline
  • Mydriatics
    • Cyclopentolate
    • Homatropine
    • Tropicamide
  • Plants
    • Amanita muscaria (fly agaric)
    • Amanita pantherina (panther mushroom)
    • Arctium lappa (burdock root)
    • Atropa belladonna (deadly nightshade)
    • Cestrum nocturnum (night blooming jessamine)
    • Datura suaveolens (angel's trumpet)
    • Datura stramonium (jimson weed)
    • Hyoscyamus niger (black henbane)
    • Lantana camara (red sage)
    • Solanum carolinensis (wild tomato)
    • Solanum dulcamara (bittersweet)
    • Solanum pseudocapsicum (Jerusalem cherry)
    • Solanum tuberosum (potato)
    • Miscellaneous, including carbamazepine, cyclobenzaprine, and orphenadrine

More on Toxicity, Anticholinergic

Overview: Toxicity, Anticholinergic
Differential Diagnoses & Workup: Toxicity, Anticholinergic
Treatment & Medication: Toxicity, Anticholinergic
Follow-up: Toxicity, Anticholinergic
References
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References

  1. Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline]. [Full Text].

  2. Bryson P. Comprehensive Review in Toxicology. Hemisphere Publishing; 1989:3-11, 75-83, 566-7.

  3. Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. Apr 2000;35(4):374-81. [Medline].

  4. Daunderer M. Physostigmine salicylate as an antidote. Int J Clin Pharmacol Ther Toxicol. Dec 1980;18(12):523-35. [Medline].

  5. Ellenhorn MJ, Barceloux D. Medical toxicology. In: Elsevier Applied Science. Elsevier Science; 1988:16, 25-31, 83, 93, 106-9, 117, 407, 472, 474, 592, 666.

  6. Goldfrank L, Flomenbaum N, Lewin N, et al. Anticholinergic poisoning. J Toxicol Clin Toxicol. Mar 1982;19(1):17-25. [Medline].

  7. Haddad LM, Winchester JF, eds. Clinical Management of Poisoning and Drug Overdose. 2nd ed. WB Saunders Co; 1990:861-7, 83, 231, 385.

  8. Kaye S. Handbook of Emergency Toxicology: A Guide for the Identification, Diagnosis and Treatment of Poisoning. 5th ed. Charles C Thomas Pub Ltd; 1988:31-44.

  9. Lu F. Basic Toxicology: Fundamentals, Target Organs, and Risk Assessment. 3rd ed. Taylor & Francis; 1996:52-4, 65, 279-84.

  10. McFarland KA. Anticholinergic poisoning. In: Emergency Medicine. 1998.

  11. Nice A, Leikin JB, Maturen A, et al. Toxidrome recognition to improve efficiency of emergency urine drug screens. Ann Emerg Med. Jul 1988;17(7):676-80. [Medline].

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Further Reading

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Keywords

anticholinergic toxicity, anticholinergic syndrome, ACS, anticholinergic drug ingestions, anticholinergic drug overdose, anticholinergic poisoning, antihistamines, antipsychotics, antispasmodics, cyclic antidepressants, mydriatics, atropine, scopolamine, glycopyrrolate, benztropine, trihexyphenidyl, chlorpheniramine, cyproheptadine, doxylamine, hydroxyzine, dimenhydrinate, diphenhydramine, meclizine, promethazine, chlorpromazine, clozapine, mesoridazine, olanzapine, quetiapine, thioridazine, clidinium, dicyclomine, hyoscyamine, oxybutynin, propantheline, amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, cyclopentolate, homatropine, tropicamide, Amanita muscaria, fly agaric, Amanita pantherina, panther mushroom, Arctium lappa, burdock root, Atropa belladonna, deadly nightshade, Cestrum nocturnum, night blooming jessamine, Datura suaveolens, angel's trumpet, Daturastramonium, jimson weed, Hyoscyamus niger, blackhenbane, Lantana camara, red sage, Solanum carolinensis, wild tomato, Solanum dulcamara, bittersweet, Solanum pseudocapsicum, Jerusalem cherry, Solanum tuberosum, potato, carbamazepine, cyclobenzaprine, orphenadrine

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Contributor Information and Disclosures

Author

John J Bruns, Jr, MD, Clinical Assistant Professor, Department of Emergency Medicine, Mount Sinai School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

David C Lee, MD, Research Director, Department of Emergency Medicine, Assistant Professor, North Shore University Hospital and New York University Medical School
David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD, ABAT is a member of the following medical societies: American Academy of Clinical Toxicology and American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center
Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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