safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2019-7-4-190-199safetyrisk-154Research ArticleОБЗОРЫREVIEWSБезопасность применения ингибиторов холинэстеразы и антагонистов NMDA-рецепторов для лечения пациентов с деменциейSafety of Cholinesterase Inhibitors and NMDA Receptors Antagonists for the Treatment of Patients with Dementiahttps://orcid.org/0000-0001-7168-3636ПереверзевА. П.PereverzevA. P.

Переверзев Антон Павлович, канидат медицинских наук

ул. 1-ая Леонова, д. 16, Москва, 129226

Anton Р. Pereverzev, Cand. Sci. (Med.). 

1-st Leonova St., Moscow 129226

acchirurg@mail.ruhttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна, доктор медицинских наук, профессор

ул. 1-ая Леонова, д. 16, Москва, 129226

Olga D. Ostroumova, Dr. Sci. (Med.), Professor

1-st Leonova St., Moscow 129226

ostroumova.olga@mail.ruhttps://orcid.org/0000-0002-4193-688XТкачеваО. Н.TkachevaO. N.

Ткачева Ольга Николаевна, доктор медицинских наук, профессор

ул. 1-ая Леонова, д. 16, Москва, 129226

Olga N. Tkacheva, Dr. Sci. (Med.), Professor

1-st Leonova St., Moscow 129226

acchirurg@mail.ruhttps://orcid.org/0000-0002-1628-5093КотовскаяЮ. В.KotovskayaY. V.

Котовская Юлия Викторовна, доктор медицинских наук, профессор

ул. 1-ая Леонова, д. 16, Москва, 129226

Yulia V. Kotovskaya, Dr. Sci. (Med.), Professor

1-st Leonova St., Moscow 129226

acchirurg@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации, обособленное структурное подразделение «Российский геронтологический научно-клинический центр»РоссияPirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Russian Clinical and Research Center of GerontologyRussian Federation20190711201974190199Copyright © Переверзев А.П., Остроумова О.Д., Ткачева О.Н., Котовская Ю.В., 20192019Переверзев А.П., Остроумова О.Д., Ткачева О.Н., Котовская Ю.В.Pereverzev A.P., Ostroumova O.D., Tkacheva O.N., Kotovskaya Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/154

Для лечения деменции и болезни Альцгеймера в настоящее время применяются лекарственные средства из группы ингибиторов холинэстеразы и/или неконкурентный антагонист NMDA-рецепторов мемантин. Назначение этих лекарственных средств способствует временному улучшению или стабилизации нарушений памяти и других когнитивных функций, регрессу поведенческих нарушений, снижению зависимости пациента от окружающих, но в то же время может приводить к развитию нежелательных реакций. Цель работы: анализ информации о безопасности лекарственных средств из группы ингибиторов холинэстеразы (донепезил, ривастигмин, галантамин) и неконкурентного антагониста NMDA-рецепторов мемантина, применяемых для лечения деменции. Показано, что на фоне стимуляции холинорецепторов наблюдаются такие нежелательные реакции, как сокращение и сужение зрачка (миоз), увеличение кривизны хрусталика, спазм аккомодации (нарушение зрения и увеличение риска падений), снижение частоты сердечных сокращений (брадикардия) и угнетение проведения импульсов по проводящей системе сердца, повышение тонуса бронхов, желудочно-кишечного тракта, желчного и мочевого пузыря, снижение тонуса сфинктеров пищеварительного тракта и мочевого пузыря, усиление секреции экзокринных и желез желудка, ажитация, спутанность сознания. Блокада NMDA-рецепторов и, соответственно, нарушение обмена глутамата в центральной нервной системе являются причиной нейротоксичности антагонистов NMDA-рецепторов, а также могут вызывать головокружение, чувство усталости, галлюцинации, сонливость, спутанность сознания. В случае развития нежелательных реакций по возможности следует прекратить прием препарата или уменьшить его дозу, при передозировке или иной необходимости — назначить симптоматическую терапию. Информация о безопасности ингибиторов холинэстеразы и антагонистов NMDAрецепторов имеет важное практическое значение для специалистов здравоохранения, в том числе в области фармаконадзора, так как позволяет оценить возможные риски, связанные с применением препаратов этих групп. Кроме того, информация может быть использована для оптимизации и индивидуализации схем фармакотерапии пациентов с деменцией, в том числе для разработки отечественных протоколов по депрескрайбингу препаратов (научно обоснованной практике отмены, замены или постепенного снижения дозы) у лиц пожилого и старческого возраста.

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 authors declare that there are no conflicts of interest present.