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’)10.30895/2312-7821-2021-9-2-69-74safetyrisk-219Research ArticleОБЗОРЫREVIEWSПоражение аорты при терапии фторхинолонамиFluoroquinolone-Induced Aortic Injuryhttps://orcid.org/0000-0001-7826-9657ИзможероваН. В.IzmozherovaN. V.

Изможерова Надежда Владимировна, д-р мед. наук, доцент

ул. Репина, д. 3, Екатеринбург, 620028

Nadezhda V. Izmozherova, Dr. Sci. (Med.), Associate Professor

3 Repina St., Ekaterinburg 620028

nadezhda_izm@mail.ruhttps://orcid.org/0000-0001-6216-2468ПоповА. А.PopovArtem A.

Попов Артем Анатольевич, д-р мед. наук, доцент

ул. Репина, д. 3, Екатеринбург, 620028

Artem A. Popov, Dr. Sci. (Med.), Associate Professor

3 Repina St., Ekaterinburg 620028

art_popov@mail.ruhttps://orcid.org/0000-0001-7907-2629БахтинВ. М.BakhtinV. M.

Бахтин Виктор Михайлович

ул. Репина, д. 3, Екатеринбург, 620028

Viktor M. Bakhtin

3 Repina St., Ekaterinburg 620028

bakhtin.v95@mail.ruhttps://orcid.org/0000-0003-3801-5577МарковаЕ. В.MarkovaE. V.

Маркова Евгения Вадимовна

ул. Репина, д. 3, Екатеринбург, 620028

Evgenia V. Markova

3 Repina St., Ekaterinburg 620028

ms.marevad@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Уральский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияUral State Medical UniversityRussian Federation202127042021926974Copyright © Изможерова Н.В., Попов А.А., Бахтин В.М., Маркова Е.В., 20212021Изможерова Н.В., Попов А.А., Бахтин В.М., Маркова Е.В.Izmozherova N.V., Popov A.A., Bakhtin V.M., Markova E.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/219

По данным клинических исследований, применение антибактериальных препаратов группы фторхинолонов ассоциировано с развитием таких редких, но серьезных нежелательных реакций, как поражения аорты. Цель работы: анализ данных научной литературы о риске поражения аорты при терапии фторхинолонами. В результате проведенного аналитического обзора установлено, что факторами риска поражения аорты при терапии фторхинолонами являются мужской пол, возраст старше 45 лет, фоновое заболевание аорты, а также курение и ассоциированный с ним атеросклероз. Спектр клинико-морфологических форм фторхинолон-ассоциированного поражения аорты включает дилатацию (развитие аневризмы), диссекцию (расслоение) и разрыв. Анализ данных о связи поражения аорты с применением наиболее часто назначаемых фторхинолонов (ципрофлоксацина, левофлоксацина и моксифлоксацина) показал, что случаи аневризмы и диссекции развивались преимущественно на фоне использования левофлоксацина, а реже всего — ципрофлоксацина. Механизм повреждения аорты связан с активацией фторхинолонами матриксных металлопротеиназ, разрушающих эластические элементы стенки сосуда, а также со снижением экспрессии лизилоксидазы и нарушением образования коллагена. Способность фторхинолонов к комплексообразованию с ионами магния снижает доступность этого элемента для ферментных систем клетки, что приводит к задержке синтеза структурных белков внеклеточного матрикса, активации матриксных металлопротеиназ и кальцификации стенки сосуда. Для профилактики, раннего выявления и своевременной коррекции указанных нарушений необходимо повышение информированности врачей различных специальностей о возможности развития поражений аорты при применении антибиотиков группы фторхинолонов.

According to clinical studies, the use of fluoroquinolone antibacterial agents is associated with such rare, but serious adverse reactions as aortic injuries. The aim of the study was to analyse scientific literature data on the risk of aortic injury during fluoroquinolone treatment. The analytical review showed that the risk factors for fluoroquinolone-induced aortic injury are male gender, age over 45 years, underlying aortic disease, as well as smoking and associated atherosclerosis. Clinical and morphological forms of fluoroquinolone-associated aortic injuries include dilatation (aneurysm development), dissection, and rupture. The analysis of data on the association between aortic injuries and the use of most common fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) showed that development of aneurysm and dissection was most often observed for levofloxacin, and least often for ciprofloxacin. The mechanism of aortic injury is due to fluoroquinolone-mediated activation of matrix metalloproteinases which damage elastic components of vascular walls, as well as reduction in lysyl oxidase expression and collagen synthesis. The ability of fluoroquinolones to form complexes with magnesium ions reduces the availability of magnesium to the cell enzyme systems, which delays synthesis of extracellular matrix structural proteins, leads to metalloproteinase activation and calcification of the vascular walls. Prevention, early detection, and timely management of the above-mentioned issues depend on the awareness of different medical specialists about the risks of aortic injury associated with the use of fluoroquinolone antibiotics.

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The authors declare that there are no conflicts of interest present.