Practice Essentials

Anticholinergic syndrome (ACS) is produced by the inhibition of cholinergic neurotransmission at muscarinic receptor sites. It may follow the ingestion of a wide variety of prescription and over-the-counter medications.^{[1, 2, 3]}This syndrome may be caused by intentional overdose, inadvertent ingestion, medical noncompliance, or geriatric polypharmacy; systemic effects also have resulted from topical eye drops.

Signs and symptoms

Clinical manifestations are caused by CNS effects, peripheral nervous system effects, or both. Common manifestations are as follows:

Flushing
Dry skin and mucous membranes
Mydriasis with loss of accommodation
Altered mental status (AMS)
Fever

Additional manifestations include the following:

Sinus tachycardia
Decreased bowel sounds
Functional ileus
Urinary retention
Hypertension
Tremulousness
Myoclonic jerking

See Presentation for more detail.

Diagnosis

No specific diagnostic studies exist for anticholinergic overdoses. Laboratory studies that may be helpful include the following:

Acetaminophen and salicylate screening – in all intentional poisonings
Blood and urine cultures – in febrile patients
Serum chemistry and electrolyte analysis
Electrolyte and arterial blood gas (ABG) analysis
Urine pregnancy test – in all women of childbearing age

Additional studies that may be useful are as follows:

CT of the head and MRI imaging – for patients in whom AMS is insufficiently explained by the ingested agent or who are unresponsive to appropriate intervention
ECG – for all patients with suspected toxic ingestions
Lumbar puncture – for patients with fever and AMS in whom CNS infection is suspected as a possible etiology

See Workup for more detail.

Management

Patients presenting with anticholinergic toxicity should be transported to the nearest emergency facility with advanced life support (ALS) capabilities.

In patients with recent (< 1 hour), clinically significant ingestions that are anticipated to result in moderate-to-severe anticholinergic toxicity, single-dose activated charcoal may be administered to minimize absorption of the ingested medication. In patients with depressed level of consciousness or impaired airway reflexes, definitive control of the airway (endotracheal intubation with a cuffed endotracheal tube) should be obtained prior to adminstration of activated charcoal via orogastric tube to minimize the risk of charcoal aspiration.

The antidote for anticholinergic toxicity is physostigmine salicylate. Most patients can be safely treated without it, but it is recommended for those who have tachydysrhythmia with subsequent hemodynamic compromise, intractable seizure, severe agitation or psychosis, or some combination thereof. Contraindications to physostigmine include asthma, diabetes mellitus, and cardiovascular disease.^[4]

See Treatment and Medication for more detail.

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.

Etiology

Anticholinergic syndrome may be caused by intentional overdose, inadvertent ingestion, medical noncompliance, or 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.^{[1, 2, 3]}

Intentional abuse with hallucinogenic plants (eg, Datura stramonium [jimson weed]) and mushrooms 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.

Anticholinergic drugs include the following:

Atropine, scopolamine
Glycopyrrolate
Benztropine, trihexyphenidyl

In addition to anticholinergics, drug classes that have anticholinergic properties include antihistamines, antipsychotics, antispasmodics, cyclic antidepressants, and mydriatics. Furthermore, several varieties of plants and mushrooms contain anticholinergic substances.

Antihistamines with anticholinergic properties include the following:

Chlorpheniramine
Cyproheptadine
Doxylamine
Hydroxyzine
Dimenhydrinate
Diphenhydramine
Meclizine
Promethazine

Antipsychotics with anticholinergic properties include the following:

Chlorpromazine
Clozapine
Mesoridazine
Olanzapine
Quetiapine
Thioridazine
Asenapine ^[5]

Antispasmodics with anticholinergic properties include the following:

Clidinium
Dicyclomine
Hyoscyamine
Oxybutynin
Propantheline

Cyclic antidepressants with anticholinergic properties include the following:

Amitriptyline
Amoxapine
Clomipramine
Desipramine
Doxepin
Imipramine
Nortriptyline
Protriptyline

Mydriatics with anticholinergic properties include the following:

Cyclopentolate
Homatropine
Tropicamide

Miscellaneous drugs with anticholinergic properties include the following:

Carbamazepine
Cyclobenzaprine
Orphenadrine

Plants with anticholinergic properties include the following:

Atropa belladonna (deadly nightshade)
Brugmansia spp.
Datura suaveolens (angel's trumpet)
Datura stramonium (jimson weed)
Hyoscyamus niger (black henbane)

Mushrooms with anticholinergic properties include:

Clitocybe spp
Inocybe spp

Epidemiology

In 2020, the American Association of Poison Control Centers (AAPC) National Poison Data System Annual Report documented 2465 single exposures to anticholinergic drugs, excluding cough and cold preparations. Unintentional ingestions accounted for 2020 presentations. There were 166 cases of moderate morbidity (requiring specific treatment), 25 cases of major morbidity (life-threatening), and 2 deaths reported in 2020.^[6]Patients with severe central manifestations (eg, hallucinations, psychoses, seizures, coma) have the highest morbidity rates.

Antihistamines also have anticholinergic properties. In 2020, the AAPCC documented 71,456 single exposures to antihistamines, with 28,418 specific to diphenhydramine. A total of 11 deaths were attributed to antihistamine toxicity; 9 were specifically diphenhydramine related.^[6]

Clinical Presentation

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