What are the key differences between cholinergic, anticholinergic, sympathomimetic, and opioid toxidromes?

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Key Differences Between Major Toxidromes

The four major toxidromes (cholinergic, anticholinergic, sympathomimetic, and opioid) can be distinguished by their characteristic clinical presentations, which guide rapid identification and appropriate management of poisoned patients. 1, 2

Cholinergic Toxidrome

Key Features:

  • Vital Signs: Bradycardia, hypotension
  • Mental Status: Confusion, seizures
  • SLUDGE Symptoms:
    • Salivation
    • Lacrimation
    • Urination
    • Defecation
    • GI upset (nausea, vomiting, diarrhea)
    • Emesis
  • Other Features: Miosis (pinpoint pupils), bronchospasm, bronchorrhea, muscle fasciculations, weakness

Common Causes:

  • Organophosphates and carbamates (pesticides)
  • Certain mushrooms
  • Nerve agents
  • Physostigmine and other cholinesterase inhibitors

Treatment:

  • Atropine 2-4 mg IV initially, repeated every 5-10 minutes until secretions are controlled
  • Pralidoxime (2-PAM) 1000-2000 mg IV for organophosphate poisoning only
  • Supportive care including airway management 2, 3

Anticholinergic Toxidrome

Key Features:

  • Vital Signs: Tachycardia, hyperthermia, hypertension
  • Mental Status: Agitation, delirium, hallucinations, seizures
  • Classic Signs: "Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter"
    • Hyperthermia
    • Mydriasis (dilated pupils)
    • Dry mucous membranes, decreased sweating
    • Flushed skin
    • Altered mental status
  • Other Features: Urinary retention, decreased bowel sounds, myoclonus

Common Causes:

  • Antihistamines
  • Atropine and other belladonna alkaloids
  • Tricyclic antidepressants
  • Certain plants (jimsonweed, nightshade)

Treatment:

  • Supportive care
  • Benzodiazepines for agitation
  • Physostigmine for severe cases (1-2 mg IV) with caution 1, 3

Sympathomimetic Toxidrome

Key Features:

  • Vital Signs: Tachycardia, hypertension, hyperthermia
  • Mental Status: Agitation, paranoia, hallucinations
  • Other Features: Mydriasis (dilated pupils), diaphoresis, tremor, hyperreflexia, seizures

Common Causes:

  • Amphetamines
  • Cocaine
  • Caffeine/theophylline
  • Synthetic cathinones ("bath salts")

Treatment:

  • Sedation for agitation (benzodiazepines preferred)
  • Rapid external cooling for hyperthermia
  • Vasodilators for coronary vasospasm
  • Avoid prolonged physical restraint without sedation 1

Opioid Toxidrome

Key Features:

  • Vital Signs: Respiratory depression, bradycardia, hypotension
  • Mental Status: CNS depression, sedation, coma
  • Classic Triad: Respiratory depression, miosis (pinpoint pupils), decreased level of consciousness
  • Other Features: Decreased bowel sounds, hypothermia

Common Causes:

  • Heroin, morphine, fentanyl
  • Prescription opioid analgesics
  • Methadone

Treatment:

  • Airway management and ventilatory support
  • Naloxone 0.04-2 mg IV/IM/IN, may require repeated doses
  • Caution with naloxone in opioid-dependent patients (can precipitate withdrawal) 1

Differential Diagnostic Considerations

Overlapping Features:

  • Pupil Size:

    • Miosis: Opioids, cholinergics
    • Mydriasis: Anticholinergics, sympathomimetics
  • Heart Rate:

    • Tachycardia: Anticholinergics, sympathomimetics
    • Bradycardia: Cholinergics, opioids (late)
  • Mental Status:

    • Agitation/delirium: Anticholinergics, sympathomimetics
    • Depression/coma: Opioids, severe cholinergic

Key Distinguishing Features:

  • Secretions:

    • Increased: Cholinergic (SLUDGE)
    • Decreased: Anticholinergic (dry)
  • Skin:

    • Diaphoretic: Sympathomimetic, cholinergic
    • Dry: Anticholinergic
  • Bowel Sounds:

    • Hyperactive: Cholinergic
    • Hypoactive: Anticholinergic, opioid

Clinical Pitfalls and Caveats

  1. Mixed toxidromes are common with polysubstance ingestions or certain medications with multiple mechanisms (e.g., tricyclic antidepressants)

  2. Toxidromes may be masked by:

    • Co-ingestions
    • Underlying medical conditions
    • Delayed absorption of sustained-release formulations
    • Time since exposure
  3. Pediatric and elderly patients may present with atypical features

  4. Always maintain a broad differential diagnosis, as many medical conditions can mimic toxidromes 1

  5. Treatment should focus on supportive care first, with specific antidotes used when indicated and available 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Cholinergic Overdose Syndrome and Serotonin Syndrome Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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