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肺靶向治疗在治疗 COVID-19 相关 ARDS 中的应用。文献回顾。

Pulmonary artery targeted therapy in treatment of COVID-19 related ARDS. Literature review.

机构信息

Department of Neurosurgery and Neurology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, K. Ujejskiego 75, 85-168 Bydgoszcz, Poland; Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland.

Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090 Bydgoszcz, Poland.

出版信息

Biomed Pharmacother. 2022 Feb;146:112592. doi: 10.1016/j.biopha.2021.112592. Epub 2021 Dec 25.

Abstract

INTRODUCTION

The most grievous complication of the COVID-19 is the acute respiratory distress syndrome. A specific, rescue treatment for rapidly deteriorating patients should emerge to improve respiratory function and help patients to survive the most challenging period. Drugs used in targeted therapy of pulmonary arterial hypertension (PAH) appears to be suitable for this task and this article describes their potential for treatment of severe cases of COVID-19.

METHODS

The authors reviewed the following databases for randomized controlled trials, reviews and meta-analyses published up to July 2020: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. The authors included every study contributory to the assessment of the potential of drugs used in targeted PAH therapy in treatment of COVID-19.

RESULTS

Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, riociguat and prostacyclin have proven ani-inflammatory effect and reduce pulmonary artery blood pressure, lung oedema and remodelling. Bosentan shows antiviral properties and sildenafil, as well as epoprostenol, inhibits apoptosis of lung epithelial cells. Among patients with lung lesions the decrease of pulmonary blood pressure can lead to increase of ventilation/perfusion mismatch and decrease of blood oxygenation.

CONCLUSIONS

Among all assessed drugs bosentan, sildenafil and epoprostenol appear to be most promising and a combination of these drugs should be considered due to synergism. The targeted PAH therapy in treatment of COVID-19 associated ARDS could be a useful tool saving lives of patients with severe SARS-CoV-2 infection, however, its introduction should be investigated and monitored very carefully as it can lead to transient deterioration of patient condition.

摘要

引言

COVID-19 最严重的并发症是急性呼吸窘迫综合征。应该出现一种针对病情迅速恶化患者的特定治疗方法,以改善呼吸功能并帮助患者度过最具挑战性的时期。肺动脉高压(PAH)靶向治疗中使用的药物似乎适合这项任务,本文描述了它们在治疗严重 COVID-19 病例中的潜力。

方法

作者检索了以下数据库中的随机对照试验、综述和荟萃分析,检索截至 2020 年 7 月:Pubmed、Scopus、Google Scholar、Cochrane Database 和 ClinicalKey。作者纳入了有助于评估靶向 PAH 治疗药物在 COVID-19 治疗中潜力的每一项研究。

结果

内皮素受体拮抗剂、磷酸二酯酶 5 抑制剂、利奥西呱和前列环素已被证明具有抗炎作用,可降低肺动脉血压、肺水肿和重塑。波生坦具有抗病毒特性,西地那非和依前列醇抑制肺上皮细胞凋亡。在有肺部病变的患者中,肺动脉血压的降低可导致通气/灌注不匹配增加和血氧饱和度降低。

结论

在所有评估的药物中,波生坦、西地那非和依前列醇似乎最有前途,由于协同作用,应考虑联合使用这些药物。针对 COVID-19 相关 ARDS 的 PAH 靶向治疗可能是一种挽救严重 SARS-CoV-2 感染患者生命的有用工具,然而,应该非常仔细地研究和监测其应用,因为它可能导致患者病情暂时恶化。

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