Toxcards: Sympathomimetic vs. Anticholinergic Toxidromes

Author: Patrick C Ng, MD (Chief Resident, San Antonio Military Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


Case Presentation

An 18 year old female is brought in by EMS after an unknown suicidal ingestion. She is confused, her pupils are dilated, and she is tachycardic. She has no tremors or rigidity. She has no history of chronic substance abuse or withdrawal.


How can you distinguish an anticholinergic vs sympathomimetic toxidrome?


There are overlapping signs and symptoms in both toxidromes; historical clues and a physical exam targeting the pupils, skin, GI and GU systems can reveal the toxidrome.

anticholinergic sympathomimetic toxidromes

-Antihistamines, antidepressants, scopolamine, hyoscyamine, atropine, and plants containing anticholinergic alkaloids (Datura, Belladonna) can precipitate an anticholinergic syndrome.1

-Treatment for anticholinergic syndrome is mainly supportive. Benzodiazepines are the mainstay treatment. Physostigmine is given to diagnose and treat anticholinergic delirium. A widely followed recommendation is that Physostigmine should not be given if there are signs of sodium channel blockade on the EKG.2 However newer research is challenging this notion.3

-TCA overdose can present with an anticholinergic toxidrome. Physostigmine is contraindicated in TCA overdose due to the concern for Na channel blockade causing myocardial depression.4

-Amphetamines, synthetic cannabinoids and methylxanthines like caffeine, nicotine, and theophylline can precipitate a sympathomimetic syndrome.5

-Treatment for sympathomimetic syndrome is mainly supportive with IV fluids and benzodiazapines. Beta blockers should be avoided in patients presenting with sympathomimetic syndrome secondary to cocaine use secondary to the possible effect of unopposed alpha-stimulation.

-The differential diagnosis for sympathomimetic syndrome include anticholinergic syndrome, sedative-hypnotic withdrawal, alcohol withdrawal, neuroleptic malignant syndrome, opioid withdrawal, and serotonin syndrome. Medical conditions like hypoglycemia, heat stroke, encephalitis, pheochromocytoma, thyoid storm, and sepsis can also mimic sympathomimetic syndrome.5


Table source: Santos C, Olmedo R. Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition and Treatment. Emergency Medicine Practice Guidelines. Evidence Based Medicine Journal. March 2017;19(7):1-20

Main Point:

The clinical picture of sympathomimetic and anticholinergic can appear similar. Both may have agitation, confusion, delirium, seizures, tachycardia, hypertension, fever, and mydriasis. Distinguishing characteristics for anticholinergic syndrome are dry skin, absent bowel sounds, and urinary retention. Remember the colloquial description for anticholinergic toxicity; “Blind as a bat, mad as a hatter, red as a beet, hot as Hades (or hot as a hare), dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.” Both sympathomimetic and anticholinergic syndrome respond well to benzodiazepines. Physostigmine can be used to treat delirium associated with anticholinergic syndrome after checking the EKG for signs of Na channel blockade.


  1. Curry S, et al. Chapter 14: Neurotransmitters and Neuromodulators. Chapter in Goldfrank’s Toxicologic Emergencies, 10th edition. New York: McGraw-Hill Education, 2015, p173-201
  2. Burns MJ, Linden CH, Graudins A et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35:374-81.
  3. Rasimas JJ, Sachdeva KK, Donovan JW. Revival of an antidote: bedside experience with physostigmine. J Amer Acad Emerg Psychiatr. 2014;12:5–24.
  4. Suchard JR: Assessing physostigmine’s contraindication in cyclic antidepressant ingestions. J Emerg Med. 2003; 25:185-91.
  5. Santos C, Olmedo R. Sedative-Hypnotic Drug Withdrawal Syndrome: Recognition and Treatment. Emergency Medicine Practice Guidelines. Evidence Based Medicine Journal. March 2017;19(7):1-20

5 thoughts on “Toxcards: Sympathomimetic vs. Anticholinergic Toxidromes”

    1. There are a lot of unfounded dogmas in toxicology and medicine in general. This certainly may be one of them. However it will take more than a review paper or a couple of FOAM articles to get rid of this one. Its pretty entrenched in the medical literature and in the practice of physicians. Even the American Heart Association has pretty strong language against the use of beta blockers in cocaine ingestions. To go contrary would be considered by most “against the standard of care” which many physicians do not feel comfortable with. However I agree unfounded dogma needs to die at a certain point. I just don’t think we are there yet on this issue. Maybe it has a role in refractory HTN or tachycardia that does not respond to benzos, nitro, or CCBs. Phenotolamine is also an option, but yes getting it from your pharmacy can be difficult. The vast majority of hypertensive patients 2/2 stimulants usually respond very well to benzos. I’ve rarely needed to give nitro or CCB and I haven’t had a single patient yet not respond to any of these three. Since we have available options that are known to be safe and effective I’m not sure why the need to look into this one so much other than for academic purposes. So yes this maybe dogma but with effective and safe options out there I’m not sure its worth the fight. But for those who have it in them to kill this dogma – you have my respect.

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