An unusual cardiovascular adverse effect of donepezil

Çelik, İbrahim Etem; Acar, Berrin; S, Cay

doi:10.1111/imj.12827

Cited by 8 publications

(4 citation statements)

References 5 publications

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“…This condition is an atrial arrhythmia which presents with at least three distinctly different P wave morphologies. 151 Negative chronotropic effects contribute to detrimental health outcomes including syncope, pacemaker insertion, falls, fractures, hospitalization. 147,[152][153][154] However, there is controversy that AChEIs result in negative chronotropic effects.…”

Section: Cardiovascular Adverse Effectsmentioning

confidence: 99%

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Ruangritchankul¹,

Chantharit²,

Srisuma³

et al. 2021

TCRM

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The rising of global geriatric population has contributed to increased prevalence of dementia. Dementia is a neurodegenerative disease, which is characterized by progressive deterioration of cognitive functions, such as judgment, language, memory, attention and visuospatial ability. Dementia not only has profoundly devastating physical and psychological health outcomes, but it also poses a considerable healthcare expenditure and burdens. Acetylcholinesterase inhibitors (AChEIs), or so-called anti-dementia medications, have been developed to delay the progression of neurocognitive disorders and to decrease healthcare needs. AChEIs have been widely prescribed in clinical practice for the treatment of Alzheimer's disease, which account for 70% of dementia. The rising use of AChEIs results in increased adverse drug reactions (ADRs) such as cardiovascular and gastrointestinal adverse effects, resulting from overstimulation of peripheral cholinergic activity and muscarinic receptor activation. Changes in pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PGx), and occurrence of drug interactions are said to be major risk factors of ADRs of AChEIs in this population. To date, comprehensive reviews in ADRs of AChEIs have so far been scarcely studied. Therefore, we aimed to recapitulate and update the diverse aspects of AChEIs, including the mechanisms of action, characteristics and risk factors of ADRs, and preventive strategies of their ADRs. The collation of this knowledge is essential to facilitate efforts to reduce ADRs of AChEIs.

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Section: Cardiovascular Adverse Effectsmentioning

confidence: 99%

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Ruangritchankul¹,

Chantharit²,

Srisuma³

et al. 2021

TCRM

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show abstract

“…This would suggest a similar mechanism to that of current primary treatments for AD patients, including donepezil, tacrine, rivastigmine and galantamine - nonselective AChE inhibitors. These drugs have been tested and show efficacy in treating AD-related cognitive symptoms, however not without the side effects including, night time disturbances [ 7 ], gastrointestinal [ 6 ] and cardiovascular complications [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…These muscarinic agonist drugs act through the inhibition of acetylcholinesterase (AChE), responsible for breaking down acetylcholine (ACh) in the neural synapse. However, the effectiveness of these drugs differs from patient to patient, and adverse effects have been reported including, gastrointestinal symptoms [ 6 ], night time disturbances [ 7 ] and cardiovascular complications [ 8 ]. Thus, the administration of a naturally occurring substance, which potentially has the same alleviative potency as a synthetic psychotropic drug, would be of great interest to the medical field.…”

Section: Introductionmentioning

confidence: 99%

GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice

Reid

Ryu

Kim³

et al. 2018

Nutr Res Pract

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BACKGROUND/OBJECTIVESFermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia.MATERIALS/METHODSWe examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period.RESULTSFL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively.CONCLUSIONOverall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

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“…Several published case reports have described donepezil-related symptoms, such as dizziness, syncope, sinus bradycardia, and sick sinus syndrome. [1][2][3] However, no reports have examined serum concentrations of donepezil in patients who developed acute cholinergic syndrome by prescribed doses of the drug. Acute cholinergic syndrome, which is triggered by cholinergic excess, is associated with muscarinic, nicotinic, and central muscarinic symptoms.…”

mentioning

confidence: 99%

Acute cholinergic syndrome in a patient taking the prescribed dose of donepezil for Alzheimer's disease

et al. 2020

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An unusual cardiovascular adverse effect of donepezil

Cited by 8 publications

References 5 publications

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice

Acute cholinergic syndrome in a patient taking the prescribed dose of donepezil for Alzheimer's disease

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