May 2019 By

Anticholinergic and Cholingeric Toxicity

Anticholinergic and Cholinergic Drugs are commonly used in medicine. Due to their mechanism of action, they can have a variety of side effects and toxicity profile, and it is important to know why this happens. When thinking about side effects, it is most important to focus on how it affects the sympathetic and parasympathetic nervous system.

Anticholinergic vs. Cholinergic Overdose

Anticholingeric Overdose Cholinergic Overdose
Summary A precipitous drop in acetylcholine, leading to a drop in PNS activity, making things as “dry as the dessert” A flood of acetylcholine, making things as “wet as the ocean”
  • ”Blind as a bat” (blurred vision, dilated pupils)
  • “Dry as a bone” (dry mouth and skin)
  • “Red as a beet” (vasodilation/flushing)
  • “Mad as a hatter” (confusion, delirium, agitation, hallucinations)
  • “Hot as a hare” (hyperthermia)
  • “And the heart runs alone” (tachycardia)

Central nervous symptoms of an overdose includes: mild cognitive impairment (+/- confusion), hallucinations, tremors, ataxia.

SLUDGE mnemonic:
  • Salivation
  • Lacrimation
  • Urination
  • Diaphoresis
  • GI upset
  • Emesis

Bradycardia and pin-point pupils can result as well.

Examples Anticholinergics (atropine, benztropine), antihistamines (diphenhydramine), low-potency antipsychotics (clozapine, quetiapine), tricyclic antidepressants Muscarinic receptor agonists (pilocarpine, methacholine), acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), organophosphate insecticides (sarin gas)
  • Benzodiazepines for seizures and agitation
  • Physostigmine is the main treatment: it inhibits acetylcholinesterase activity to increase the amount ACh available (EXCEPT in cases of TCA overdose, where it is CONTRAINDICATED, because it will lead to life-threatening bradyarrhythmias)
  • Atropine 2mg every few minutes until symptoms are relieved
  • Since atropine only targets the muscarinic receptors, the nicotinic receptors are left untouched. Therefore to treat the neuromuscular symptoms (weakness/fasciculations) you need to treat with pralidoxime which inactivates the agent at the neuromuscular junction (NMJ)
Anticholingeric Delirium