Suspected donepezil toxicity: A case report

Abstract

Donepezil is an acetylcholinesterase inhibitor (AChEI) that prevents the breakdown of acetylcholine, a neurotransmitter, which is depleted in patients with Alzheimer's disease and dementia. 1 There are few reports showcasing donepezil toxicity in the literature and even less that display a coinciding beta-blocker toxicity. 2-8 This case highlights symptoms representative of a donepezil toxicity and risks that may occur even at the manufacturer's recommended doses. The American Geriatrics Society's Beer's list recognizes donepezil as a high-risk medication in older adults due to increased rates of orthostatic hypotension and bradycardia within this population. 9 Some common (>10%) adverse reactions of donepezil include nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia. Other less common (1%-10%) adverse effects are insomnia, emesis, gastritis, hypertension, syncope, bradycardia, chills, generalized coldness, pain, dizziness, abnormal gait, confusion, fatigue, diaphoresis, abdominal pain, bloating, and constipation and were reported to occur more often in females of advancing age. 10 Toxicity symptoms reported in other case reports included: nausea, vomiting, confusion, somnolence, diaphoresis and bradycardia with greater prominence at higher donepezil doses. 2-8 In addition, postmarketing data have revealed hyperglycemia and hypothermia reported in less than 1% of patients. 10 One of the dose-related signs of toxicity in animals was lower body surface temperature. Like donepezil toxicity, altered mental status and bradycardia commonly occur with beta-blocker toxicity. Hypothermia can occur with both agents; however, it is less prevalent in beta-blocker toxicity. Other effects seen with beta-blocker toxicity include hypotension, respiratory depression, seizure, hypoglycemia, and bronchospasm. 11,12 When AChEIs are co-administered with heart rate-lowering agents like beta-blockers, a theoretical risk of enhanced bradycardia exists. 12 Beta-blockers lower the heart rate by blocking beta-1 receptors and impeding the action of epinephrine and norepinephrine. 13 AChEIs increase acetylcholine at the synapses and affect the parasympathetic innervation of the heart, resulting in decreased sinoatrial-and atrioventricular node conduction and decreased heart rate. 14

Acetylcholinesterase Inhibitory Activities of Essential Oils from Vietnamese Traditional Medicinal Plants

“…Currently, there are disadvantages associated with current Alzheimer’s disease chemotherapeutics. For example, tacrine was observed to have serious side effects such as elevated liver transaminases and gastrointestinal problems [ 10 , 11 ]; donepezil has been reported to exhibit toxicity similar to beta-blocker overdose and colitis [ 12 ]; the toxicity of rivastigmine is thought to be similar to that of other carbamates and organophosphates with features of muscarinic and nicotinic stimulation [ 13 ]. Essential oils and their chemical constituents have been shown to have effects on the central nervous system, including in the treatment of Alzheimer’s disease and Parkinson’s disease [ 14 ].…”

Effects of Donepezil on the Musculoskeletal System in Female Rats

“…In adult mice, donepezil impaired neuromuscular function by generating prolonged aftercontractions after brief stimulation at moderate frequencies and by prolonging synaptic depolarizations associated with an increased incidence of spontaneous muscle contractions [79]. Donepezil has also been shown to exert adverse effects on muscles, manifested through muscle cramps in patients [80,81]. On the other hand, donepezil promoted muscle differentiation independent of its AchE-inhibitory action in C2C12 mouse myoblast cells in vitro and in a mouse model of a cardiotoxin-based skeletal muscle injury in vivo [82].…”