Kotfis Katarzyna, Lechowicz Kacper, Drożdżal Sylwester, Niedźwiedzka-Rystwej Paulina, Wojdacz Tomasz K, Grywalska Ewelina, Biernawska Jowita, Wiśniewska Magda, Parczewski Miłosz
Department of Anesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.
Department of Pharmacokinetics and Monitored Therapy, Pomeranian Medical University, 70-111 Szczecin, Poland.
Pharmaceuticals (Basel). 2021 Jan 17;14(1):71. doi: 10.3390/ph14010071.
In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.
2020年3月，世界卫生组织（WHO）宣布由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）为全球大流行病。该疾病的临床病程不可预测，但可能导致严重急性呼吸道感染（SARI）和肺炎，进而引发急性呼吸窘迫综合征（ARDS）。研究表明，肺纤维化可能是COVID-19的主要长期并发症之一。在动物模型中，已证实使用螺内酯是预防肺纤维化的一种重要药物。通过作为盐皮质激素受体（MR）拮抗剂和雄激素抑制剂的双重作用，螺内酯可在COVID-19感染方面带来显著益处。螺内酯在减轻肺水肿方面的主要作用对COVID-19 ARDS可能也有益处。螺内酯是一种广为人知、广泛使用且安全的抗高血压和抗雄激素药物。它通过拮抗盐皮质激素受体（MRs）发挥保钾利尿作用。螺内酯和坎利酸钾发挥联合多效作用，可能通过抗雄激素、MR阻断、抗纤维化和抗高炎症作用为COVID-19肺炎患者带来治疗益处。有人提出，螺内酯可能因其对肾素-血管紧张素-醛固酮系统（RAAS）和ACE2表达的有利多效作用、跨膜丝氨酸蛋白酶2（TMPRSS2）活性的降低以及抗雄激素作用，预防COVID-19感染中的急性肺损伤，因此它可能被证明可为重症肺炎高危患者提供额外保护。有必要开展未来的前瞻性临床试验来评估其治疗潜力。
