What is the overview of anticholinergic (Anticholinergic) toxicity?

From the Guidelines

Anticholinergic toxicity should be managed with supportive care, including cooling measures for hyperthermia, IV fluids for dehydration, and cardiac monitoring, with physostigmine considered as an antidote in severe cases, as it can help overcome receptor blockade by inhibiting acetylcholinesterase and increasing acetylcholine levels 1. The classic presentation of anticholinergic toxicity follows the mnemonic "Red as a beet, dry as a bone, hot as a hare, blind as a bat, mad as a hatter, full as a flask" and includes symptoms such as:

• Hyperthermia
• Mydriasis (dilated pupils)
• Dry mucous membranes
• Flushed skin
• Altered mental status
• Urinary retention
• Decreased bowel sounds
• Tachycardia Common causative agents of anticholinergic toxicity include:
• Antihistamines (diphenhydramine)
• Tricyclic antidepressants (amitriptyline)
• Antipsychotics (olanzapine)
• Plants like jimsonweed Treatment considerations for anticholinergic toxicity include:
• Discontinuing the precipitating agent
• Providing supportive care
• Administering physostigmine as an antidote in severe cases, with a typical dose of 1-2 mg IV slowly 1
• Using benzodiazepines for agitation and seizures
• Considering activated charcoal if the ingestion was recent and the airway is protected It is essential to note that physostigmine should be used cautiously and is contraindicated in patients with cardiac conduction abnormalities or tricyclic antidepressant overdose due to the risk of seizures and asystole 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Physostigmine Salicylate Injection is a reversible anticholinesterase which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. The anticholinergic syndrome has both central and peripheral signs and symptoms. Central toxic effects include anxiety, delirium, disorientation, hallucinations, hyperactivity and seizures. Severe poisoning may produce coma, medullary paralysis and death Peripheral toxicity is characterized by tachycardia, hyperpyrexia, mydriasis, vasodilation, urinary retention, diminution of gastrointestinal motility, decrease of secretion in salivary and sweat glands, and loss of secretions in the pharynx, bronchi, and nasal passages Numerous drugs and some plants produce the anticholinergic syndrome either directly or as a side effect; this undesirable or potentially dangerous phenomenon may be brought about by either therapeutic doses or overdoses of the drugs. Such drugs include among others, atropine, other derivatives of the belladonna alkaloids, tricyclic antidepressants, phenothiazines, and antihistamines.

Anticholinergic toxicity can be caused by various drugs, including atropine, tricyclic antidepressants, phenothiazines, and antihistamines. The symptoms of anticholinergic toxicity can be divided into:

• Central toxic effects:
  • Anxiety
  • Delirium
  • Disorientation
  • Hallucinations
  • Hyperactivity
  • Seizures
  • Coma
  • Medullary paralysis
• Peripheral toxic effects:
  • Tachycardia
  • Hyperpyrexia
  • Mydriasis
  • Vasodilation
  • Urinary retention
  • Diminution of gastrointestinal motility
  • Decrease of secretion in salivary and sweat glands
  • Loss of secretions in the pharynx, bronchi, and nasal passages Physostigmine Salicylate Injection can reverse both central and peripheral anticholinergia 2.

From the Research

Anticholinergic Toxicity Overview

• Anticholinergic toxicity is a well-described and relatively common condition, characterized by both central and peripheral physical findings 3, 4.
• The anticholinergic toxidrome can cause a myriad of signs and symptoms, including agitation, seizures, hyperthermia, cardiac dysrhythmias, and death 5.
• Central anticholinergic syndrome is characterized primarily by signs and symptoms consistent with hyperactive delirium, while peripheral anticholinergia includes mydriasis and blurred vision, tremors, ataxia, fever/hyperthermia, flushed and dry skin, dry oral mucosa, decreased bowel sounds, constipation, and urinary retention 4.

Treatment of Anticholinergic Toxicity

• Physostigmine is a tertiary acetylcholinesterase inhibitor that can be used to assist in the diagnosis and management of severe anticholinergic toxicity 3, 4.
• However, the supply of physostigmine has been limited, and rivastigmine, a long-acting acetylcholinesterase inhibitor, is a potential alternative 6.
• Rivastigmine has been shown to be safe and effective in treating anticholinergic toxicity, with no adverse events reported in a case series of 12 patients 6.
• Benzodiazepines are also commonly used in the treatment of anticholinergic toxicity, and may be used in conjunction with physostigmine or rivastigmine 3, 5.

Adverse Effects of Physostigmine

• Physostigmine can cause adverse effects, including hypersalivation, nausea and vomiting, seizures, and symptomatic bradycardia 7.
• However, significant adverse effects associated with the use of physostigmine are infrequently reported, and seizures are self-limited or resolved with benzodiazepines 7.
• Physostigmine should be avoided in patients with QRS prolongation on EKG, and caution should be used in patients with a history of coronary artery disease and overdoses with QRS prolonging medications 7.

Management of Anticholinergic Toxicity

• Emergency physicians should be familiar with how to manage anticholinergic toxicity, including recognizing the classic clinical presentation, common medications and substances that may lead to anticholinergic toxicity, and ECG findings that require specific therapy 5.
• Simulation cases can be an effective way to teach learners about the management of anticholinergic toxicity, and can help to improve their ability to evaluate and manage patients presenting with this condition 5.