RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that has emerged and rapidly spread across the world. The COVID-19 severity is associated to viral pneumonia with additional extrapulmonary complications. Hyperinflammation, dysfunctional immune response and hypercoagulability state are associated to poor prognosis. Therefore, the repositioning of multi-target drugs to control the hyperinflammation represents an important challenge for the scientific community. Cilostazol, a selective phosphodiesterase type-3 inhibitor (PDE-3), is an antiplatelet and vasodilator drug, that presents a range of pleiotropic effects, such as antiapoptotic, anti-inflammatory, antioxidant, and cardioprotective activities. Cilostazol also can inhibit the adenosine uptake, which enhances intracellular cAMP levels. In the lungs, elevated cAMP promotes anti-fibrotic, vasodilator, antiproliferative effects, as well as mitigating inflammatory events. Interestingly, a recent study evaluated antiplatelet FDA-approved drugs through molecular docking-based virtual screening on viral target proteins. This study revealed that cilostazol is a promising drug against COVID-19 by inhibiting both main protease (Mpro) and Spike glycoprotein, reinforcing its use as a promising therapeutic approach for COVID-19. Considering the complexity associated to COVID-19 pathophysiology and observing its main mechanisms, this article raises the hypothesis that cilostazol may act on important targets in development of the disease. This review highlights the importance of drug repurposing to address such an urgent clinical demand safely, effectively and at low cost, reinforcing the main pharmacological actions, to support the hypothesis that a multi-target drug such as cilostazol could play an important role in the treatment of COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , Cilostazol/uso terapêutico , Inibidores da Fosfodiesterase 3/uso terapêutico , SARS-CoV-2 , HumanosRESUMO
Atherosclerosis is a multifactorial chronic disease, initiated by an endothelial dysfunction. Adenosine and its analogs can change a variety of inflammatory diseases and has shown important effects at different disease models. Inosine is a stable analogous of adenosine, but its effects in inflammatory diseases, like atherosclerosis, have not yet been studied. The aim of this study was to evaluate the pharmacological properties of inosine, administered sub chronically in a hypercholesterolemic model. Male Wistar rats were divided into four groups: control group (C) and control + inosine (C + INO) received standard chow, hypercholesterolemic diet group (HCD) and HCD + inosine (HCD + INO) were fed a hypercholesterolemic diet. At 31st experimentation day, the treatment with inosine was performed for C + INO and HCD + INO groups once daily in the last 15 days. We observed that the hypercholesterolemic diet promoted an increase in lipid levels and inflammatory cytokines production, while inosine treatment strongly decreased these effects. Additionally, HCD group presented a decrease in maximum relaxation acetylcholine induced and an increase in contractile response phenylephrine induced when compared to the control group, as well as it has presented an enhancement in collagen and ADP-induced platelet aggregation. On the other hand, inosine treatment promoted a decrease in contractile response to phenylephrine, evoked an improvement in endothelium-dependent vasorelaxant response and presented antiplatelet properties. Moreover, inosine activated eNOS and reduced p38 MAPK/NF-κB pathway in aortic tissues. Taken together, the present results indicate inosine as a potential drug for the treatment of cardiovascular disorders such as atherosclerosis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Inosina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Humanos , Inosina/farmacologia , Interleucina-6/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue , Vasodilatadores/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Abstract Chloroquine (CQ) and Hydroxychloroquine (HCQ) are antimalarial drugs, with anti-inflammatory properties that justify their use in the treatment of systemic lupus erythematosus and rheumatic diseases. A pandemic caused by the new coronavirus led the entire world's scientific community to look for drugs already available on the market, capable of exercising beneficial actions in the fight against the disease. Preliminary studies in patients, as well as in vitro studies, suggested possible therapeutic effects associated with the use of HCQ and CQ in the treatment of COVID-19. Despite controversies over the effects of these drugs in combating the "cytokine storm" associated with COVID and the dismal of results in different clinical trials in Brazil, their use has been encouraged and several ongoing investigative studies are underway. In addition to the possible beneficial effects on the prognosis of patients with SARS-CoV-2, such drugs include varied effects on the cardiovascular system, ranging from positive developments related to their vasodilator properties to potential negative effects, such as cardiotoxicity. This work presents the main effects exerted by these drugs on the cardiovascular system, in order to contribute to a scientific discussion about the repurposing of these drugs in the context of COVID-19.
Assuntos
Cloroquina/toxicidade , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/toxicidade , Interações MedicamentosasRESUMO
Este trabalho faz uma revisão sobre o tema de tortuosidade coronariana abordando várias situações na prática clínica aonde a tortuosidade coronariana pode desempenhar um papel relevante e procura avaliar se há correlação entre tortuosidade coronariana e a presença de isquemia miocárdica em pacientes sem obstruções coronarianas fazendo uma busca na literatura das evidências científicas. Livro-texto de Fisiologia em Cardiologia com estudo da circulação coronariana, artigos teóricos com estudos de Hemodinâmica, Dinâmica de Fluidos e de Mecânica e artigos experimentais com simulação em computadores serviram de sustentação para a formulação da hipótese a ser verificada
Assuntos
Humanos , Masculino , Feminino , Idoso , Circulação Coronária , Vasos Coronários/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Fatores Etários , Envelhecimento , Ecocardiografia/métodos , Coração , Hipertensão/complicações , Consumo de Oxigênio/fisiologia , Fluxo Sanguíneo Regional/fisiologiaRESUMO
É relatado um caso de morte súbita (MS) registrada através de eletrocardiografia dinâmica (Holter) e demonstrada como uma rara manifestaçäo da disfunçäo do nódulo sinusal. É destacada a fundamental importância do método para avaliar os fatores precipitantes da arritmia fatal