Safety of Cholinesterase Inhibitors and NMDA Receptors Antagonists for the Treatment of Patients with Dementia

Abstract

For the treatment of dementia and Alzheimer’s disease, acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or the non-competitive inhibitor of N-methyl-D-aspartate receptors (NMDA receptors) memantine are currently used. The administration of these drugs can help temporarily improve or stabilize memory impairments and other cognitive functions, regress behavioral disorders, reduce the patient’s dependence on others, but at the same time can lead to the development of adverse drug reactions. The aim of this study was to analyze the information on the safety of acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the non-competitive inhibitor of NMDA receptors used to treat dementia. It was shown that stimulation of cholinergic receptors can lead to adverse drug reactions as contraction and narrowing of the pupil (miosis), an increase in lens curvature, accommodation spasm (visual impairment and an increased risk of falls), a decrease in heart rate (bradycardia) and inhibition of conduction of impulses through the conducting system heart, increased tone of the bronchi, gastrointestinal tract, gall and bladder, decreased tone of the sphincters of the digestive tract and bladder, increased secretion of exocrine and glands of the stomach, agitation, confusion. Blockade of NMDA receptors due to impairment of glutamate metabolism in the central nervous system may be the cause of neurotoxicity of NMDA receptor antagonists, and also causes dizziness, feeling of tiredness, hallucinations, drowsiness, and confusion. In case of development of adverse reactions, if possible, it is necessary to stop using the drug or reduce its dose, in case of an overdose or other need, prescribe symptomatic therapy. Information on the safety of cholinesterase inhibitors and NMDA receptor antagonists presented in the article is of practical importance for healthcare professionals, as it allows them to assess the possible risks associated with the use of drugs of these groups more accurately. In addition, the information can be used to optimize and individualize the pharmacotherapy regimens for patients with dementia, including the development of domestic protocols for the deprescribing of drugs (evidence-based practice of withdrawal, replacement or gradual dose reduction) in the elderly.

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“…The use of acetylcholinesterase inhibitors (DP, RSM, GAL) and/or the non-competitive inhibitor of NMDAR (memantine) and anti-amyloid monoclonal antibodies (aducanumab and lecanemab) in dementia and AD, would be able to contribute to the temporary improvement or consolidation of the losses of memory and other cognitive functions, to the decline of behavioral disorders, and to limiting the patient’s dependence on aids; at the same time, however, these agents can bring great discomfort through the multitude of adverse reactions [ 147 ].…”

Effect of Multiple Medicines on Dementia Initial Treatment: Experience and Thinking

“…Drug interventions play an important role in anti-dementia treatment, and they mainly include anti-dementia and psychoactive drugs. 8 , 9 Anti-dementia drugs include cholinesterase inhibitors (ChEI) (such as donepezil, rivastigmine, and galantamine) to treat mild to moderate dementia. Often, dementia is accompanied by behavioral and psychological symptoms of dementia (BPSD).…”