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Dementia
Published in Henry J. Woodford, Essential Geriatrics, 2022
Common adverse effects reported with donepezil include diarrhoea, muscle cramps, fatigue, nausea, vomiting and insomnia; and nausea and vomiting with galantamine or rivastigmine.115 Cholinesterase inhibitors are a cause of urinary incontinence, which can lead to the illogical addition of bladder anticholinergic drugs in a prescribing cascade.119 Their use is also associated with an increased risk of syncope compared to placebo (OR 1.53; 95% CI 1.02–2.30).120 All of these potentially offset the small beneficial cognitive effects.
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
Cholinesterase inhibitors may be effective for cognitive, neuropsychiatric, and motor symptoms. Rivastigmine has been shown to improve attention and hallucinations, delusions, and anxiety.31 Donepezil has been shown to improve cognition as well.32 Patients initiating cholinesterase inhibitors should be monitored for GI distress, weight loss, and other adverse effects. Drugs with anticholinergic properties should be avoided. Memantine has also been tried in the treatment of DLB, however, data are conflicting.
Cholinergic Agonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar
The clinical uses of anti-ChEs are as follows: Neostigmine: At the end of an operation, it reverses the action of nondepolarizing neuromuscular blockers.Pyridostigmine or neostigmine: Treatment of myasthenia gravis.Edrophonium: A short-acting drug, given intravenously in the management of myasthenia gravis and to differentiate between muscle paralysis due to myasthenia gravis or cholinergic crisis at the motor end plate.Donepezil: In Alzheimer’s disease.Ecothiopate: In glaucoma, as an eye drops (Katzung et al., 2009).
Extemporaneous combination of donepezil and memantine to treat dementia in Alzheimer disease: evidence from Italian real-world data
Published in Current Medical Research and Opinion, 2023
Alessandro Padovani, Serena Falato, Valeria Pegoraro
Adherence to therapy is the extent to which patients follow their medication schedules as prescribed by their doctors46. Treatment adherence was evaluated in terms of proportion of days covered (PDC), which corresponds to the total days of supply of medication dispensed over the length of the corresponding follow-up (i.e. 180 days). The PDC metric has been advocated by the Pharmacy Quality Alliance as the preferred indicator for estimating adherence to therapies for chronic diseases47 and it is known to provide a more conservative estimate of medication adherence compared to other measures in cases of concomitant multiple medications usage48. The number of days supplied by each prescription was calculated by dividing the total amount of active drug in each prescription by the corresponding daily maintenance dose (DMD). The maximum daily dosage for memantine is 20 mg. Patients shall assume 5 mg, 10 mg, and 15 mg of memantine once daily during the first, second, and third week of treatment respectively; starting from the fourth week of treatment, patients shall assume 20 mg of memantine once daily49; a dosage of 20 mg was considered as the DMD for memantine. The maximum daily dosage for donepezil is 10 mg. Patients shall assume 5 mg of donepezil once daily for at least the first month of treatment, then the doctor can decide to increase the daily dosage to 10 mg50; a dosage of 10 mg was considered as the DMD for donepezil. Days of supply contributed to the numerator only when memantine and donepezil overlapped.
Long term use of donepezil and QTc prolongation
Published in Clinical Toxicology, 2021
Jason Kho, Adam Ioannou, Amit K. J. Mandal, Andrew Cox, Ashraf Nasim, Sofia Metaxa, Constantinos G. Missouris
Donepezil is an acetylcholinesterase inhibitor primarily used to treat mild to moderate Alzheimer’s dementia (AD). While the neurocognitive benefits of donepezil are well documented, its adverse effects on cardiac conduction remain unclear. Several case studies have reported QT prolongation and subsequent Torsades de Pointes (TdP) associated with donepezil use in patients with AD [1–4], while others have reported bradycardia and PR prolongation, resulting in subsequent medication cessation [5,6]. Smaller-scale studies to date have shown that donepezil is relatively safe to use in the elderly population. Common parasympathetic side-effects have been associated with its use, but importantly these small-scale observational studies have not reported any sinister repolarisation abnormalities such as significant QT prolongation, subsequent arrhythmia, or syncopal episodes [7–9].
An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease
Published in Expert Opinion on Drug Safety, 2020
Andrea Haake, Kevin Nguyen, Lauren Friedman, Binu Chakkamparambil, George T Grossberg
The current FDA-approved treatment options for Alzheimer’s disease are considered symptomatic therapies. There are no disease-modifying drugs currently shown to help stop the underlying pathogenesis of AD [35]. Various studies of donepezil have shown some promising, potential disease-modifying effects of the drug compared to placebo. Donepezil’s potential disease-modifying effects are highlighted in (Table 2). A 2014 randomized control trial of 216 subjects with mild cognitive impairment (MCI) used magnetic resonance imaging to determine whether donepezil 10 mg/day slowed the rate of hippocampal atrophy after one year compared to placebo [36]. The rate of hippocampal atrophy was significantly reduced in the donepezil treatment group (annual percentage change = −1.89%) compared to placebo (−3.47; p < 0.001). Despite this structural benefit, there were no significant differences between treatment groups on neuropsychological test outcomes.