Cholinergic symptoms with low serum cholinesterase from therapeutic cholinesterase inhibitor toxicity
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American Journal of Emergency Medicine
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Cholinergic symptoms with low Serum cholinesterase from therapeutic cholinesterase inhibitor toxicity
Abstract
Although cholinesterase inhibitors have been frequently used in the treatment of Alzheimer disease, its effects on serum cholinester- ase concentrations have been rarely described. We described significant depression of serum cholinesterase levels due to cholin- esterase inhibitor toxicity from redundant use of donepezil and rivastigmine in a 78-year-old man. Recovery of serum cholinesterase level was noted upon drug discontinuation and cholinergic symptom resolution. Serum cholinesterase level can be used as a biomarker for central cholinesterase inhibitor toxicity.
The central nervous system cholinesterase inhibitors have been used for more than a decade to slow the progression of mental decline in patients with Alzheimer disease and other forms of dementia [1]. By acting to increase the acetylcholine concentration in the brain, peripheral cholinergic effects have rarely been described along with concomitant inhibition of serum cholinesterase enzyme. We describe such an effect in an individual receiving 2 such cholinesterase inhibitors, displaying peripheral cholinergic effects and decreased serum cholines- terase levels with resolution of both upon drug discontinuation.
The patient is a 78-year-old man with a history of Parkinson disease and dementia due to Lewy body disease, admitted with profound lethargy and confusion for several days. His medications included Metoprolol XL (25 mg daily), donepezil (10 mg/d, started 7 months prior to admission), rivastigmine patch (9.5 mg, started 7 days prior to admission), trazodone (25 mg at night), warfarin (5 mg/d) for Paroxysmal atrial fibrillation, and carbidopa-levadopa (25-100 mg tablets twice a day). He was noted to have pinpoint pupils (b 1 mm in diameter with a baseline reported to be 2-3 mm in diameter) along with Sinus bradycardia with a pulse rate of 50 beats/min and was minimally responsive and incoherent on physical examination. He was also afebrile with a blood pressure of 118/60 mm Hg and no respiratory depression. The laboratory tests, which included thyroid studies, complete blood count, and complete metabolic profile, were unremarkable. The electroencephalogram revealed nonspecific findings consistent with a generalized process with bilateral slowing in the theta range. Computed tomography of the brain revealed nonspecific degenerative changes of the brain. The finding from the urine drug screen was negative. Of interest is that the patient’s serum cholinesterase was 1820 U/L (reference range, 4900-11 900 U/L).
The rivastigmine, metoprolol, and donepezil were all discontinued. Within 3 days, the bradycardia and pinpoint pupils resolved; additionally, the patient’s mental status returned to baseline. A repeat serum cholinesterase level was 3190 U/L 5 days after admission. The patient was discharged on a rivastigmine patch to a skilled nursing facility after a 6-day hospitalization.
Overall, there was a temporal relationship in this patient receiving multiple cholinesterase medications between resolution of clinical peripheral cholinergic symptoms (bradycardia, pinpoint pupils), encephalopathy, and normalization of serum cholinesterase concentrations and drug removal. Historically, these drugs have been quite tolerable with a reported dropout rate due to drug adverse effect reported to be 7% in a meta-analysis of 16 randomized, double-blind, placebo-controlled drug trials involving 5159 patients [2]. The most common adverse effects are usually nonspecific gastrointestinal in origin (nausea, vomiting, or diarrhea) [1,2]. These drugs can increase the risk of bradycardia with a doubling of the risk of hospitalization for bradycardia noted a recent Canadian-based study [3].
Animal (rodent) studies have demonstrated a decrease in cerebral and blood cholinesterase activity by 66% and 32%, respectively; however, this has not been studied in humans [4]. It should be noted that cholinesterase levels (both central and serum) are lower in patients with dementia, thus placing them at some risk for cholinergic toxicity [5]. Thus, it certainly appears that dementia patients may be at a particular risk for developing cholinergic symptoms from these drugs. We believe that serum cholinesterase can be a biomarker for central cholinesterase inhibitor toxicity when administering agents that modulate acetylcholine.
Jerrold B. Leikin, MD
NorthShore University HealthSystem-OMEGA
Glenbrook Hospital
Glenview, IL Pritzker School of Medicine University of Chicago
Chicago, IL E-mail address: [email protected]
Victoria Braund, MD Pritzker School of Medicine University of Chicago
Chicago, IL Department of Medicine
NorthShore University HealthSystem
Glenbrook Hospital
Glenview, IL
Carol DesLauris, PharmD, DABAT
Chicago, IL
http://dx.doi.org/10.1016/j.ajem.2013.12.048
0735-6757/(C) 2014
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