eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Anticholinergic

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

Updated: Dec 7, 2009

Introduction

Background

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

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 (AAPCC), more than 2.4 million cases of human poison exposure were reported to 61 US poison control centers in 2007.1

In 2007, the AAPCC National Poison Data System Annual Report documented 8582 single exposures to anticholinergic drugs. Unintentional ingestions accounted for 8109 presentations, intentional ingestions accounted for 297 presentations, and adverse reactions occurred in 141. Moderate morbidity (requiring specific treatment) was reported in 186 cases, major morbidity (life-threatening) in 13, and no deaths were reported.1

In 2007, the AAPCC National Poison Data System Annual Report documented 78,130 symptomatic antihistamine presentations with 33,143 specific to diphenhydramine. A total of 5 deaths were attributed to antihistamine toxicity of which 3 were specifically diphenhydramine related.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
[ CLOSE WINDOW ]

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

  2. 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].

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

  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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

anticholinergic toxicity, anticholinergic syndrome, ACS, anticholinergic syndrome symptoms, anticholinergic syndrome treatment, anticholinergic syndrome causes, anticholinergic drug ingestions, anticholinergic drug overdose, anticholinergic poisoning, antihistamines, antipsychotics, antispasmodics, cyclic antidepressants, diphenhydramine

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

John J Bruns Jr, MD, MPH, 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, Associate 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, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: 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, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.