Physostigmine

Reversible acetylcholinesterase inhibitor that increases synaptic acetylcholine at both nicotinic and muscarinic receptors. 

• Main role to ameliorate delirium as a result of the anticholinergic (more accurately, antimuscarinic) toxidrome resultant from the blockade of muscarinic receptors by agents such as atropine, antihistamines, amongst other xenobiotics. 

• Can be used diagnostically for undifferentiated altered mental status where anticholinergic delirium is suspected. 

• No randomized controlled trials have been conducted in humans demonstrating the efficacy of physostigmine.

• The principal adverse effects of physostigmine are related to cholinergic excess including bradycardia, bronchospasm, bronchorrhea, seizure, and motor weakness. Less severe symptoms are nausea, vomiting, diarrhea, miosis, tremor, and fasciculation.

• The most concerning and also controversial adverse effects of physostigmine are bradydysrhythmias and asystole in case with use for TCA poisoning

  • Avoid use in cases with bradycardia or AV block

  • Cases with QRS widening remains controversial

  • In cases with TCA toxicity target at reversing cardiac sodium channel blockade by either administration of NaHCO3 or hypertonic saline

• May be more efficacious than benzodiazepines for reversing central antimuscarinic symptoms including agitation, delirium, and/or hallucinations. and lowers risk of excessive sedation from high doses of benzodiazepine