Recurrence of Upper Gastrointestinal Bleeding After Donepezil Administration

Pipili, Chrysoula; Dasenaki, Maria

doi:10.1097/01.wad.0000213851.59119.0b

Cited by 14 publications

(16 citation statements)

References 6 publications

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“…The biological plausibility of donepezil causing GI ulceration could be due to its ulcer promoting effect through increased acid production, which is partly controlled by cholinergic vagal fibres. Only one case report has reported recurrent UGIB due to a gastric ulcer following ongoing donepezil use 11. In our case, ulcer formation could have coincided with a recent upward dose titration of donepezil.…”

Section: Discussionmentioning

confidence: 52%

Upper gastrointestinal bleed associated with cholinesterase inhibitor use

2015

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An 86-year-old man was admitted with a 3-day history of melaena and syncope. He was haemodynamically compromised and anaemic on presentation. His only medical history was mild Alzheimer's disease diagnosed 6 months prior. For this, he was on donepezil, a cholinesterase inhibitor (ChEI), with a recent dose increase 3 months earlier. After fluid resuscitation with packed red cells, an endoscopy was performed, which showed an acute duodenal ulcer. This was treated with a high-dose proton pump inhibitor. The patient recovered well and was discharged on donepezil with the addition of a gastro-protective proton pump inhibitor. In view of other absent risk factors of upper gastrointestinal haemorrhage, donepezil was the likely causative agent. ChEIs are associated with frequent side effects and increased hospitalisation due to central and peripheral increase in acetylcholine. With this case report, we review the literature of side effects related to ChEIs, where the mechanisms of action, complications and appropriate management are discussed

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Section: Discussionmentioning

confidence: 52%

Upper gastrointestinal bleed associated with cholinesterase inhibitor use

2015

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“…Controlled clinical studies with higher dose of donepezil showed an increase in the incidence of peptic ulcer disease and GI bleeding from any site (e.g., incidence of GI bleeding, donepezil 23 mg/d, 1.1%, vs 10 mg/d, 0.6%) . The product labeling of these drugs includes a warning to “monitor closely for manifestations of active or occult GI bleeding, especially in individuals at increased risk (e.g., history of ulcer disease, concomitant nonsteroidal anti‐inflammatory drug (NSAID) therapy).” Cases of upper and lower GI bleeding associated with donepezil and galantamine use have been reported from postapproval controlled and uncontrolled clinical trials and postmarketing experience …”

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confidence: 99%

“…12,14,15 Cases of upper and lower GI bleeding associated with donepezil and galantamine use have been reported from postapproval controlled and uncontrolled clinical trials and postmarketing experience. 12,14,16 A high prevalence of comorbid conditions and usage of concomitant medications may add to the risk of GI bleeding in individuals with AD. One study compared the disease burden of AD in a commercial managed care setting with that of a matched cohort aged 65 and older without AD.…”

mentioning

confidence: 99%

Incidence of Serious Upper and Lower Gastrointestinal Events in Older Adults with and without Alzheimer's Disease

Guo

Kumar

et al. 2011

J. Am. Geriatr. Soc.

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“…Patients who take donepezil may have an increased risk of bleeding (14, 16, 17). Since donepezil is an acetylcholinesterase inhibitor, we hypothesized that donepezil inhibits platelet activation.…”

Section: Resultsmentioning

confidence: 99%

“…Studies of adverse bleeding reactions to commonly used drugs can reveal novel inhibitors of platelet function (13). For example, a few case reports have suggested that acetylcholinesterase inhibitors are associated with bleeding (14, 15). Several clinical trials have examined the safety of donepezil, and one of these trials showed that donepezil increases the risk of bruising (16, 17).…”

Section: Introductionmentioning

confidence: 99%

Acetylcholine inhibits platelet activation and regulates hemostasis

Bennett

et al. 2018

Preprint

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22Word Count: 5145 23 Figure Count: 5 figures 24 25 26 42 platelets express members of the acetylcholine signaling pathway including CHRNA2, CHRNA7,43 CHRNB1, and ACHE. Platelets from mice lacking Chrna7 are hyperactive when stimulated by 44 thrombin and resistant to inhibition by acetylcholine. Furthermore, acetylcholinesterase 45 inhibitors prolonged bleeding in wild-type mice. Knockout mice lacking Chrna7 subunits of the 46 acetylcholine receptor display prolonged bleeding as well. 47 52 Abbreviations 53 NO nitric oxide 54 CHRNA7 cholinergic receptor neuronal nicotinic alpha polypeptide 7 55 GPIIbIIIA glycoprotein IIb IIIa 56 AChR acetylcholine receptors 57 AChE acetylcholinesterase 58 TRAP thrombin receptor activating peptide 6 59 PAR1 protease activated receptor 1 60 P2Y12 purinergic receptor P2Y 61 GPVI glycoprotein VI 62 NOS3 nitric oxide synthase isoform 3 63 L-NAME L-nitroarginine methyl ester

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Recurrence of Upper Gastrointestinal Bleeding After Donepezil Administration

Cited by 14 publications

References 6 publications

Upper gastrointestinal bleed associated with cholinesterase inhibitor use

Upper gastrointestinal bleed associated with cholinesterase inhibitor use

Incidence of Serious Upper and Lower Gastrointestinal Events in Older Adults with and without Alzheimer's Disease

Acetylcholine inhibits platelet activation and regulates hemostasis

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