Toxicology – Anticholinergic Syndrome

Definition

Anticholinergic syndrome is a toxidrome caused primarily by blockade of muscarinic acetylcholine receptors.

The classic presentation includes:

• Tachycardia
• Mydriasis and blurred vision
• Dry mouth and mucous membranes
• Warm, dry, flushed skin
• Decreased bowel sounds or ileus
• Urinary retention
• Agitation, delirium, and hallucinations
• Hyperthermia in more severe cases

Mechanism of Action

Antimuscarinic agents competitively inhibit acetylcholine at postsynaptic muscarinic receptors.

This reduces parasympathetic activity in the:

• Heart
• Eyes
• Sweat and salivary glands
• GI tract
• Urinary tract
• Central nervous system

Classic antimuscarinic agents do not primarily block nicotinic acetylcholine receptors.

Common Causes

Important causes include:

• First-generation antihistamines, especially diphenhydramine
• Tricyclic antidepressants
• Atropine
• Scopolamine
• Benztropine
• Oxybutynin
• Cyclobenzaprine
• Some antipsychotics
• Anticholinergic plants such as Datura and Atropa species
• Ophthalmic antimuscarinic agents

Some of these drugs have additional toxic actions. For example, severe diphenhydramine or TCA poisoning can also produce sodium-channel blockade and QRS widening.

Classic Toxidrome

A traditional mnemonic describes the syndrome as:

• “Mad as a hatter” → delirium, agitation, hallucinations
• “Hot” → hyperthermia
• “Dry as a bone” → dry skin and mucous membranes
• “Blind as a bat” → mydriasis and impaired accommodation
• “Red as a beet” → flushed skin

Not every patient develops every feature.

Vital Signs

Tachycardia is common because muscarinic blockade reduces vagal influence on the heart.

Other findings may include:

• Mild-to-moderate hyperthermia
• Hypertension from agitation
• Tachypnea
• Hypotension in severe poisoning or after seizures

HEENT

Common findings:

• Mydriasis
• Blurred vision
• Dry mouth
• Reduced secretions

Local ocular exposure can cause isolated mydriasis or anisocoria.

Skin

Typical findings are:

• Warm
• Dry
• Flushed

Reduced sweating contributes to hyperthermia.

Gastrointestinal and Genitourinary

Muscarinic blockade decreases smooth-muscle activity and secretions.

This can produce:

• Reduced bowel sounds
• Constipation
• Ileus
• Urinary retention
• Bladder distension

Neurologic Features

Central antimuscarinic toxicity may cause:

• Restlessness
• Agitation
• Confusion
• Disorientation
• Paranoia
• Visual hallucinations
• Delirium

Severe poisoning may cause:

• Seizures
• Marked hyperthermia
• Coma

Severe agitation or seizures can also produce rhabdomyolysis.

Anticholinergic vs. Sympathomimetic Toxidrome

These syndromes overlap because both can cause:

• Tachycardia
• Hypertension
• Mydriasis
• Hyperthermia
• Agitation
• Delirium

A useful distinction is the skin and GI examination:

Anticholinergic

• Dry skin
• Dry mouth
• Reduced bowel sounds
• Urinary retention

Sympathomimetic

• Diaphoresis
• Bowel sounds usually preserved or increased

Diagnosis

Diagnosis is primarily clinical, based on the toxidrome and exposure history.

Useful investigations in moderate or severe cases may include:

• ECG
• Electrolytes
• Renal function
• Glucose
• Creatine kinase when severe agitation, seizures, or hyperthermia raise concern for rhabdomyolysis
• Targeted testing for important possible coingestants

An ECG is particularly important because some anticholinergic drugs also produce cardiac sodium-channel blockade.

Management

Treatment is primarily supportive.

Important measures include:

• Airway and respiratory support when necessary
• IV fluids when clinically indicated
• External cooling for significant hyperthermia
• Cardiac monitoring in significant poisoning
• Monitoring for urinary retention
• Treatment of complications such as seizures and rhabdomyolysis

Benzodiazepines are commonly used for significant agitation and seizures.

Routine induction of vomiting and gastric lavage, as recommended in older references, are not standard modern management because their risks generally outweigh their benefits.

Activated charcoal may be considered after selected substantial recent ingestions when the airway can be safely protected.

Physostigmine

Physostigmine is a reversible acetylcholinesterase inhibitor that crosses the blood-brain barrier and can reverse both central and peripheral antimuscarinic effects.

It may be considered for severe, clinically significant antimuscarinic delirium in carefully selected patients.

It should not be treated as a routine diagnostic test for unexplained altered mental status.

Important precautions include avoiding its use when:

• TCA or another sodium-channel-blocking overdose is suspected
• The ECG shows concerning conduction abnormalities such as significant QRS widening
• The poisoning is not clearly compatible with a predominantly antimuscarinic syndrome

Because inappropriate or rapid administration can cause bradycardia, cholinergic effects, seizures, or dysrhythmias, its use requires appropriate monitoring and toxicology expertise.

Expected Course

Symptoms may develop gradually because antimuscarinic effects can slow gastrointestinal motility and delay absorption.

Many uncomplicated cases resolve within approximately a day, although severe poisoning or long-acting agents can cause symptoms lasting considerably longer.

Key Points

• Anticholinergic toxicity is primarily muscarinic receptor blockade.
• Classic findings are tachycardia + mydriasis + dry/flushed skin + decreased bowel sounds + urinary retention + delirium.
• Dry skin helps distinguish anticholinergic toxicity from the usually sweaty sympathomimetic toxidrome.
• Severe toxicity can cause hyperthermia, seizures, rhabdomyolysis, and coma.
• ECG assessment is important because some causative drugs have additional cardiotoxic effects.
• Benzodiazepines and supportive care are central to treatment.
• Physostigmine can rapidly reverse severe antimuscarinic delirium in appropriately selected patients, but it requires careful screening for contraindications.
• Older recommendations for routine ipecac or gastric lavage are obsolete.