Adverse Effects of Physostigmine

Abstract

Introduction Physostigmine is a tertiary amine carbamate acetylcholinesterase inhibitor. Its ability to cross the blood-brain barrier makes it an effective antidote to reverse anticholinergic delirium. Physostigmine is underutilized following the publication of patients with sudden cardiac arrest after physostigmine administration in patients with tricyclic antidepressant (TCA) overdoses. We completed a narrative literature review to identify reported adverse effects associated with physostigmine administration. Discussion One hundred sixty-one articles and a total of 2299 patients were included. Adverse effects occurred in 415 (18.1%) patients. Hypersalivation (206; 9.0%) and nausea and vomiting (96; 4.2%) were the most common adverse effects. Fifteen (0.61%) patients had seizures, all of which were self-limited or treated successfully without complication. Symptomatic bradycardia occurred in 8 (0.35%) patients including 3 patients with bradyasystolic arrests. Ventricular fibrillation occurred in one (0.04%) patient with underlying coronary artery disease. Of the 394 patients with TCA overdose, adverse effects were described in 14 (3.6%). Adverse effects occurred in 7.7% of patients treated with an overdose of an anticholinergic agent compared with 20.6% of patients with non-anticholinergic agents. Five (0.22%) fatalities were identified. Conclusions In conclusion, significant adverse effects associated with the use of physostigmine were infrequently reported. Seizures were self-limited or resolved with benzodiazepines, and all patients recovered neurologically intact. 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. Based upon our review, physostigmine is a safe antidote to treat anticholinergic overdose.

Physostigmine in Anticholinergic Poisoning: An Old Antidote With Resurgence

“…A 10-year retrospective cohort study was conducted in 2018 showed physostigmine to have a good safety profile with the ability to improve, and in some cases, resolved anticholinergic delirium when administered in doses less than 2mg [4]. These finding are further supported by a meta-analysis published in 2019 which analyzed data of 161 papers, and 2,299 patients concluding that physostigmine was a safe antidote to treat an anticholinergic overdose [5].…”

Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity

“…ChEI was first investigated for the treatment of AD however discontinued for multiple adverse effects (96). Ambenonium chloride AChE inhibitor and down-regulates a6b2 -nAChR mediated dopamine release.…”

Study of 3-(4’-Nitrobenzamido)coumarin using an Alzheimer’s Disease Model

“…This drug has a methylcarbamate substituent and basic groups that bind to the anionic site of AChE. The transfer of the carbamoyl group to the serine hydroxyl group of the stearic site of the enzyme is the same as observed for ACh, but the carbamylated enzyme hydrolyzes much more slowly, recovering its enzymatic activity after several minutes, instead of microseconds (Andrade and Gondal 2020;Arens and Kearney 2019). The slow recovery of the carbamylated enzyme implies that it displays a rather prolonged effect, increasing cholinergic transmission.…”