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

Abstract

Sirasa Ruangritchankul,1 Prawat Chantharit,2 Sahaphume Srisuma,3 Leonard C Gray4 1Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Ramathibodi Poison Center and Division of Clinical Pharmacology and Toxicology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Centre for Health Services Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, AustraliaCorrespondence: Sirasa RuangritchankulDivision of Geriatric Medicine, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, ThailandTel [phone]Fax [phone]Email [email protected]: 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.Keywords: older adults, dementia, acetylcholinesterase inhibitors, adverse drug reactions, drug–drug interactions

Keywords

• older adults
• dementia
• acetylcholinesterase inhibitors
• adverse drug reactions
• drug-drug interactions