Assessment of temperature‐induced hERG channel blockade variation by drugs

Kauthale, Rahul R.; Dadarkar, Shruta S.; Husain, Raushan; Karande, Vikas; Gatne, M. M.

doi:10.1002/jat.3447

Cited by 5 publications

(5 citation statements)

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“…Seriously ill patients often have comorbidities that can increase risk of serious arrhythmias. These include hypokalemia, hypomagnesemia, fever, 16 and an inflammatory state. 17 Mechanisms to minimize arrhythmia risk include: o In patients critically ill with COVID-19 infection, frequent caregiver contact may need to be minimized, so optimal electrocardiographic interval and rhythm monitoring may not be possible.…”

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confidence: 99%

Considerations for Drug Interactions on QTc in Exploratory COVID-19 Treatment

et al. 2020

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confidence: 99%

Considerations for Drug Interactions on QTc in Exploratory COVID-19 Treatment

et al. 2020

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“…Patients with severe COVID-19 disease usually have hypoxemia and may manifest hypotension and electrolyte imbalance and may need ICU admission; all of which have been shown to increase the risk of QTc prolongation in response to QT prolonging drugs [41] , [42] , [43] , [44] , [45] . Moreover, COVID-19 patients manifest fever and raised interleukin-6 levels, which have been linked to increased risk of QT prolongation in response to drugs and inflammation [46] , [47] .…”

Section: Significant Cardiac Toxicity Concernsmentioning

confidence: 99%

It is time to drop hydroxychloroquine from our COVID-19 armamentarium

Kashour

Tleyjeh

2020

Medical Hypotheses

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Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.

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“…38 É também sabido que diversos antibióticos são capazes de bloquear os canais de potássio hERG, prolongando o intervalo QT e a DPA. [39][40][41] Guo et al, 42 Outro efeito observado em alguns antibióticos é o comprometimento da função e estrutura ventricular esquerda, como observado por Zhang et al, 43 . Além disso, alguns estudos têm demonstrado que antibióticos e outros compostos naturais podem prejudicar a função mitocondrial.…”

Section: Análise Estatísticaunclassified

Avaliação dos Efeitos Cardíacos de Lectina Solúvel em Água (WSMoL) de Sementes de Moringa Oleifera

et al. 2020

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ResumoFundsamento: As sementes de Moringa oleifera, que são utilizadas para clarificação de água, contêm uma lectina chamada WSMoL que tem mostrado atividade antibacteriana e imunomoduladora in vitro. Devido ao seu valor nutritivo e potencial terapêutico, as folhas e as sementes dessa árvore são consumidas em algumas comunidades. Algumas lectinas de plantas não são tóxicas para mamíferos, mas tem sido relatado que outras são prejudiciais quando ingeridas ou administradas por outros meios.Objetivo: Como um dos passos necessários para determinar a segurança de WSMoL, nós avaliamos os possíveis efeitos cardiotóxicos desta proteína purificada.Métodos: Durante 21 dias consecutivos, a WSMoL foi administrada a camundongos por gavagem. Foram investigadas as funções eletrofisiológicas, mecânicas e metabólicas in vivo e ex vivo por meio de registros eletrocardiográficos, ressonância magnética nuclear e respirometria de alta resolução. Resultados: O tratamento com WSMoL não induziu alterações nos níveis de glicose no sangue ou peso corporal emcomparação com o grupo controle. Adicionalmente, as relações peso cardíaco/peso corporal e peso cardíaco/comprimento tibial estavam semelhantes em ambos os grupos. A ingestão de lectina também não modificou a tolerância à glicose ou resistência à insulina. Não foram observadas alterações nos parâmetros eletrocardiográficos ou na duração do potencial de ação cardíaco. Os corações dos camundongos dos grupos controle e WSMoL mostraram função ventricular esquerda preservada. Além disso, a WSMoL não induziu alterações na função mitocondrial (em todos os casos, p > 0,05). Conclusões: A administração de WSMoL demonstrou ter um perfil de segurança cardíaca. Estes resultados contribuem à avaliação de segurança do uso de sementes de M. oleifera para tratar água, visto que essa lectina está presente na preparação empregada por algumas populações com esse fim. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0) Palavras-chave: Moringa Oleifera; Lectinas; Glicosídeos; Carboidratos; Coração; Segurança Hídrica; Camundongos. AbstractBackground: Moringa oleifera seeds, which are used for water clarification, contain a lectin named WSMoL which has shown in vitro antibacterial and immunomodulatory activity. Due to their nutritional value and therapeutic potential, the leaves and seeds of this tree are eaten in some communities. Some plant lectins are non-toxic to mammals, but others have been reported to be harmful when ingested or administered by other means.Objective: As one of the steps needed to define the safety of WSMoL, we evaluated possible cardiotoxic effects of this purified protein.Methods: WSMoL was administered for 21 consecutive days to mice by gavage. Electrophysiological, mechanical, and metabolic cardiac functions were investigated by in vivo and ex vivo electrocardiographic recordings, nuclear magnetic resonance, and high-resolution respirometry. Results:The treatment with WSMoL did not induce changes in blood glucose levels or body weight in comparison with control group. Moreover, ...

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Assessment of temperature‐induced hERG channel blockade variation by drugs

Abstract: In Kauthale et al. (2015), an error was identified in the Reference list.The corrected reference is as follows:

Cited by 5 publications

References 1 publication

Considerations for Drug Interactions on QTc in Exploratory COVID-19 Treatment

Considerations for Drug Interactions on QTc in Exploratory COVID-19 Treatment

It is time to drop hydroxychloroquine from our COVID-19 armamentarium

Avaliação dos Efeitos Cardíacos de Lectina Solúvel em Água (WSMoL) de Sementes de Moringa Oleifera

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