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

Abstract

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.

Anticholinesterase and antioxidant activities of novel heterocyclic Schiff base derivatives containing an aryl sulfonate moiety

“…On the other hand, none of the aryl sulfonates had higher antioxidant activity than the standard compounds. However, it was calculated that all Schiff bases except for compound Also, the concentration-dependent percent inhibition graph of the ABTS cation radical scavenging activity of Schiff base derivatives (10)(11)(12)(13)(14)(15)(16)(17) and the standard compounds (BHT, BHA, and α-TOC) was given in Figure 2. As expected, the antioxidant activities of all tested molecules increase with increasing concentration (10, 25, 50, and 100 μM).…”

“…In this research, new heterocyclic Schiff base derivatives (10)(11)(12)(13)(14)(15)(16)(17)(18) as the target molecules were synthesized in two steps in good yields according to the previously reported methods. [61,75] In the first step, fluorine atom-containing aryl sulfonates (1-9) were readily obtained with 75%-86% yield by the treatment of nine phenolic aldehydes with 4-FBSC in the presence of triethylamine (TEA) in dichloromethane (DCM) medium under reflux conditions for 5 hr.…”

“…Among the obtained aryl sulfonates, six of them are new (3, 4, 5, 6, 8, and 9), two are known (1 and 2), and one is commercial (7). On the other hand, all heterocyclic Schiff base derivatives (9)(10)(11)(12)(13)(14)(15)(16)(17)(18) were synthesized for first time.…”

“…[9,10] The most commonly used drugs in the treatment of AD are the medicaments aimed at increasing cholinergic function. [11,12] It has been determined that these drugs have the efficacy that can partially prevent or reduce the symptoms of the disease. For this reason, many studies have been so far carried out to discover more effective new drugs that will completely prevent or partially diminish the symptoms of the disease, and thereby increase the quality of life of the patients.…”

“…Encouraged by above-mentioned information, and in a continuation of our ongoing research toward the discovery novel and potent antioxidant agents and cholinesterase inhibitors, [61] herein we have synthesized, and characterized new hybrid molecules, that is, heterocyclic Schiff base derivatives (10)(11)(12)(13)(14)(15)(16)(17)(18). These molecules were synthesized by amalgamating diverse aryl sulfonates (1-9) and 4-AAP.…”