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Updated: Jul 11, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
Evaluation of centrally acting cholinesterase inhibitor exposures in adults
Keith R McCain1, Tama S Sawyer, Henry A Spiller
1Arkansas Poison Control Center, Little Rock, AR 72205, USA. krmccain@uams.edu
Background:
There are 4 centrally acting cholinesterase inhibitors (CA-ChEI) available in the US: tacrine, galantamine, rivastigmine, and donepezil. Documented clinical experience involving exposure to these agents is limited. The lack of information makes decisions involving excessive or unintended CA-ChEI exposure difficult.
Objective:
To assess the effects, demographics, and outcomes of CA-ChEI exposures reported to US poison centers.
Methods:
A retrospective review of the Toxic Exposure Surveillance System of the American Association of Poison Control Centers data of acute and acute-onchronic exposures involving only a CA-ChEI in patients 19 years of age or older with documented medical outcomes from 2000-2005 was performed.
Results:
There were 1026 records that met criteria for this study. Patients aged 70-89 years made up 73% of reports; 69% of the patients were female. Moderate (197) and major outcomes (20) accounted for 21% of exposures. There were no deaths. Clinical effects that occurred in 5% or more of patients included vomiting (34%), nausea (28%), diarrhea (12%), dizziness/vertigo (9.9%), drowsiness/lethargy (7.7%), diaphoresis (7.4%), tremor (5.2%), and bradycardia (5%). Patients were admitted to the hospital in 19% of all exposures. Of those patients, 42% were admitted to a critical care unit. The majority (65%) of exposures were attributed to unintentional therapeutic error. Patients received at least one form of therapy in 47% of exposures, including intravenous fluid (111), antiemetic (48), atropine (17), benzodiazepine (15), oxygen (14), antihypertensive (4), pralidoxime (4), intubation (3), antihistamine (2), antiarrhythmic (1), anticonvulsant (1), and pacemaker (1).
Conclusions:
The majority of patients evaluated in this retrospective study experienced no or mild effect; however, significant or life-threatening effects were observed in a small group of patients and an appreciable number of patients were admitted to a healthcare facility.
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