Internal Medicine

Anticholinergic toxicity

  • Common emergency but rarely fatal.


Toxicity typically occurs secondary to an overdose of compounds with anticholinergic properties, although mild toxicity can even be seen as a side effect when the medication is taken appropriately. The vast majority of these agents are orally ingested.

  • Naturally compounds: Atropine, hyoscyamine, and hyoscine
    • Atropine is used as an antidote for cholinergic toxicity from organophosphates and nerve agents, and additionally for acute treatment of bradyarrhythmias.
  • Other medications: Antidepressants, antihistamines (M/C), antiparkinson drugs, antipsychotics, antispasmodics, and mydriatics
  • Many medications possess anticholinergic activity as their primary pharmacologic effect, while others exhibit these properties as adverse effects.
  • Abusive substances: Belladonna alkaloids (plants), illicit drugs contaminated with anticholinergics such as hyoscine/atropine


Muscarinic receptors:

Classical anticholinergic clinical syndrome is a manifestation of competitive antagonism of acetylcholine at peripheral and central muscarinic receptors. Muscarinic acetylcholine receptors are located in smooth muscle, the ciliary body of the eye, salivary glands, sweat glands, and in the central nervous system (CNS). Muscarinic receptors are not found at the neuromuscular junction.

There are at least five muscarinic subtypes, with distinct but overlapping tissue distributions.

  • M1 receptors (CNS)
  • M2 receptors (brain & heart)
  • M3 receptors (salivary glands)
  • M4 receptors (brain and lungs)

Most anticholinergic agents are orally ingested and their onset of action typically occurs within 2 hours. Some topical agents, such as hyoscine, can have effects lasting for over 24 hours. The effects of anticholinergic compounds on the central nervous system (CNS) can last over 8 hours, while the effects on the cardiovascular system are generally much shorter.

Clinical features

Classical presentation

Red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask
  • Flushing
  • Anhidrosis
  • Dry mucous membranes
  • Mydriasis
  • Altered mental status
  • Fever
  • Urinary retention

CNS complications:

  • Delirium, hallucinations, agitation, restlessness, confusion
  • Staccato speech: Speak in fragments of sentences that are punctuated by pauses, which interrupt, to the point of destroying the flow of your speech
  • Picking at clothing and bedding
  • Seizures and jerking movements

Cardiovascular complications:

Diphenhydramine reported in particular
  • Wide-complex tachycardia
  • QT prolongation

Case study:


Supportive care is usually all that is required for the treatment of anticholinergic toxicity.

Management of complications:

  • Agitated patient: Benzodiazepines (first-line therapy) or physostigmine (refractory cases)
  • IV fluids (for hypotension and/or suspected rhabdomyolysis)
  • Cooling measures (for hyperthermia)
  • Activated charcoal (if ingestion within one hour prior to presentation)
  • IV sodium bicarbonate (for wide-complex dysrhythmias)
  • Physostigmine (recommended in pure anticholinergic poisoning)
  • IV fat emulsion (for severe diphenhydramine overdose refractory to other interventions)

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