Anticholinergic poisoning is a potentially life-threatening toxidrome that occurs following exposure to substances that block acetylcholine at muscarinic and, to a lesser extent, nicotinic receptors. It can result in profound central and peripheral effects, ranging from delirium to life-threatening hyperthermia, arrhythmias, or seizures.

Common Sources of Anticholinergic Toxicity

Numerous prescription and over-the-counter drugs, as well as some plants and chemicals, can cause anticholinergic poisoning.

Medications:

• Antihistamines: diphenhydramine, promethazine, chlorpheniramine
• Tricyclic antidepressants: e.g. amitriptyline
• Antipsychotics: olanzapine, quetiapine, chlorpromazine, haloperidol
• Antiemetics: hyoscine hydrobromide
• Antispasmodics: oxybutynin, hyoscine butylbromide
• Antiparkinsonian agents: benztropine
• Anticonvulsants: carbamazepine
• Antimuscarinics: atropine, glycopyrrolate

Toxic Plants:

• Atropa belladonna (Deadly nightshade)
• Datura stramonium (Jimsonweed)
• Mandragora officinarum (Mandrake)

Other Sources:

• Pesticides
• Recreational drugs: e.g. PCP, ketamine (with mixed properties)
• Chemical warfare agents: Some nerve agents may show overlapping features but are primarily cholinergic in mechanism

Clinical Features: The Anticholinergic Toxidrome

Central Effects (due to CNS muscarinic blockade):

• Delirium, confusion, agitation
• Hallucinations (often visual), incoherent speech
• Myoclonus, tremor, seizures (in severe cases)
• Coma (rare)

Peripheral Effects:

• Mydriasis (dilated pupils)
• Tachycardia
• Dry mouth and skin
• Flushed skin
• Hyperthermia
• Urinary retention
• Ileus

Mnemonic Reminder:

“Red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare.”

Diagnosis

Anticholinergic poisoning is a clinical diagnosis, supported by the pattern of features above. Investigations may include:

• ECG: especially in TCA overdose (QRS widening, arrhythmias)
• Urine toxicology: limited utility, often non-specific
• CT brain: only if neurological deterioration unexplained

Management

Initial Approach:

• Use the ABCDE framework
• Ensure a calm, quiet environment to reduce agitation
• Involve a toxicologist or poisons service early

Supportive Care:

• Benzodiazepines: First-line for agitation and delirium (e.g. IV diazepam)
• IV fluids: To address dehydration and support renal clearance
• Urinary catheterisation: Often needed for urinary retention

Physostigmine – The Antidote

A reversible acetylcholinesterase inhibitor that increases synaptic acetylcholine and can reverse central and peripheral symptoms.

Indications:

• Severe agitation or delirium unresponsive to benzodiazepines
• Confirmed or strongly suspected pure anticholinergic overdose (e.g. diphenhydramine, atropine)

Contraindications:

• Bradycardia
• AV block or QRS prolongation
• Asthma or bronchospasm
• Seizure risk (e.g. tricyclic antidepressant overdose)

Dose:

• 0.5–1 mg IV over 5 minutes, repeat every 10–15 mins as needed (max 4 mg)
• Continuous monitoring is essential
• Reversal may be dramatic, but effects wear off in 1–4 hours

Adverse Effects:

• Cholinergic excess: bradycardia, bronchorrhoea, seizures
• SLUDGE symptoms: salivation, lacrimation, urination, diarrhoea, GI upset, emesis
• Rare: paradoxical worsening of agitation if used inappropriately

Key Points Most cases resolve with supportive care and sedation

• Use physostigmine cautiously and only when clearly indicated
• Avoid in mixed overdoses or where TCA involvement is suspected
• Monitor ECG and vital signs closely throughout

Summary

Anticholinergic toxicity presents with a predictable clinical toxidrome of central agitation and peripheral dryness, dilation, and hyperthermia. Prompt recognition, supportive care, and careful consideration of physostigmine can dramatically alter outcomes in severe cases. Consultation with a toxicologist is strongly advised in all but the mildest presentations.

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Thank you to the joint editorial team of MRCEM Exam Prep for this article.