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2.
BMB Rep ; 53(10): 545-550, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958120

RESUMO

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].


Assuntos
Azitromicina/efeitos adversos , Cardiotoxicidade/etiologia , Cloroquina/efeitos adversos , Células-Tronco Embrionárias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação , Animais , Arritmias Cardíacas/induzido quimicamente , Azitromicina/administração & dosagem , Diferenciação Celular , Cloroquina/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Humanos , Camundongos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico
4.
Emerg Med Clin North Am ; 38(4): 841-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981621
5.
Ann Saudi Med ; 40(5): 365-372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32954790

RESUMO

Evidence of cardiovascular complications associated with the COVID-19 global pandemic continues to evolve. These include direct and indirect myocardial injury with subsequent acute myocardial ischemia, and cardiac arrhythmia. Some results from a limited number of trials of antiviral medications, along with chloroquine/hydroxychloroquine and azithromycin, have been beneficial. However, these pharmacotherapies may cause drug-induced QT prolongation leading to ventricular arrhythmias and sudden cardiac death. Mitigation of the potential risk in these susceptible patients may prove exceptionally challenging. The Saudi Heart Rhythm Society established a task force to perform a review of this subject based on has recently published reports, and studies and recommendations from major medical organizations. The objective of this review is to identify high-risk patients, and to set clear guidelines for management of patients receiving these pharmacotherapies.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Comitês Consultivos , Antivirais/efeitos adversos , Arritmias Cardíacas/diagnóstico , Azitromicina/efeitos adversos , Betacoronavirus , Cloroquina/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/efeitos adversos , Combinação de Medicamentos , Interações Medicamentosas , Monitoramento de Medicamentos , Eletrocardiografia , Humanos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Lopinavir/efeitos adversos , Pandemias , Medição de Risco , Ritonavir/efeitos adversos , Arábia Saudita , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico
7.
Cardiol Rev ; 28(5): 266-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32769401

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a threat to the health of many humans across the world as they confront coronavirus disease 2019 (COVID-19). Previous promising in vitro data that emerged after the SARS-CoV outbreak in 2003, along with the emergent need for pharmacologic management strategies in the fight against COVID-19, prompted interest in the use of chloroquine and hydroxychloroquine across the globe. Unfortunately, the in vitro activity of these drugs did not necessarily correlate with most in vivo studies, which showed no consistent efficacy. Safety is also a major concern, with these agents having a known risk of QT prolongation and proarrhythmic effects. In addition, clinical practice guidelines provide no clear consensus on the role of chloroquine or hydroxychloroquine for the management of COVID-19. The United States Food and Drug Administration has declared that the potential benefits of these agents no longer outweigh the possible risks, and unless new emerging information suggests a more favorable risk:benefit ratio, neither chloroquine nor hydroxychloroquine should be recommended for COVID-19 treatment or prevention at this time.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Citocromo P-450 CYP2D6/metabolismo , Interações Medicamentosas , Humanos , Técnicas In Vitro , Síndrome do QT Longo/induzido quimicamente , Pandemias , Guias de Prática Clínica como Assunto , Torsades de Pointes/induzido quimicamente , Resultado do Tratamento
8.
Biomed Pharmacother ; 130: 110582, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763818

RESUMO

Given the speed of viral infection spread, repurposing of existing drugs has been given the highest priority in combating the ongoing COVID-19 pandemic. Only drugs that are already registered or close to registration, and therefore have passed lengthy safety assessments, have a chance to be tested in clinical trials and reach patients quickly enough to help in the current disease outbreak. Here, we have reviewed available evidence and possible ways forward to identify already existing pharmaceuticals displaying modest broad-spectrum antiviral activity which is likely linked to their high accumulation in cells. Several well studied examples indicate that these drugs accumulate in lysosomes, endosomes and biological membranes in general, and thereby interfere with endosomal pathway and intracellular membrane trafficking crucial for viral infection. With the aim to identify other lysosomotropic drugs with possible inherent antiviral activity, we have applied a set of clear physicochemical, pharmacokinetic and molecular criteria on 530 existing drugs. In addition to publicly available data, we have also used our in silico model for the prediction of accumulation in lysosomes and endosomes. By this approach we have identified 36 compounds with possible antiviral effects, also against coronaviruses. For 14 of them evidence of broad-spectrum antiviral activity has already been reported, adding support to the value of this approach. Presented pros and cons, knowledge gaps and methods to identify lysosomotropic antivirals, can help in the evaluation of many drugs currently in clinical trials considered for repurposing to target COVID-19, as well as open doors to finding more potent and safer alternatives.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Lisossomos/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/farmacocinética , Antivirais/efeitos adversos , Antivirais/farmacocinética , Arritmias Cardíacas/induzido quimicamente , Azitromicina/farmacocinética , Azitromicina/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cloroquina/farmacocinética , Cloroquina/uso terapêutico , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Endossomos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapêutico , Membranas Intracelulares/fisiologia , Lisossomos/química , Lipídeos de Membrana/metabolismo , Modelos Biológicos , Fosfolipídeos/metabolismo , Tensoativos/farmacocinética , Internalização do Vírus
9.
Mayo Clin Proc ; 95(8): 1696-1700, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753141

RESUMO

Among candidate drugs to treat coronavirus disease 2019 (COVID-19), the combination of hydroxychloroquine (HCQ) and azithromycin (AZ) has received intense worldwide attention. Even as the efficacy of this combination is under evaluation, clinicians have begun to use it largely. As these medications are known to prolong the QT interval, we analyzed serial electrocardiograms recorded in patients hospitalized for COVID-19 pneumonia and treated with HCQ + AZ. Fifty consecutive patients received the combination of HCQ (600 mg/d for 10 days) and AZ (500 mg/d on day 1 and 250 mg/d from day 2 to day 5). Twelve-lead electrocardiograms were recorded before treatment, at day 3, at day 5, and at discharge. The median age of patients was 68 years (interquartile range, 53-81 years); 28 (56%) were men. The main comorbidities were hypertension (36%; n=18) and diabetes (16%; n=8). The mean corrected QT (QTc) interval was 408 ms at baseline and increased up to 437 ms at day 3 and to 456 ms at day 5. Thirty-eight patients (76%) presented short-term modifications of the QTc duration (>30 ms). Treatment discontinuation was decided in 6 patients (12%), leading to QTc normalization in 5 of them. No deaths and no cardiac arrhythmic events were observed in this cohort. Our report confirms that a short duration treatment with HCQ + AZ modifies the QTc interval. The treatment had to be discontinued for QTc modifications in 12% of patients. Nevertheless, in inpatients hospitalized for COVID-19, we did not observe any clinically relevant consequences of these transitory modifications. In conclusion, when patients are treated with HCQ + AZ, cardiac monitoring should be regularly performed and hospital settings allow monitoring under in safe conditions.


Assuntos
Antivirais/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Azitromicina/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Azitromicina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Eletrocardiografia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Resultado do Tratamento
10.
J Cardiovasc Pharmacol Ther ; 25(6): 497-502, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32700555

RESUMO

In recent months, the new coronavirus SARS-CoV-2 has emerged as a worldwide threat with about 4.2 million confirmed cases and almost 300 000 deaths. Its major clinical presentation is characterized by respiratory symptoms ranging from mild cough to serve pneumonia with fever and potentially even death. Until today, there is no known medication to improve clinical symptoms or even prevent or fight the infection. The search for a useful vaccination is ongoing and it will probably not be available before the end of 2020. In this review, we highlight hydroxychloroquine (HCQ) as a potential agent to prevent coronavirus disease 2019 (COVID-19) and reduce as well as shorten clinical symptoms. Moreover, it might serve as a potential post-exposition prophylaxis. Although it has been used in the treatment of rheumatoid arthritis, discoid or systemic lupus erythematosus, and malaria prophylaxis and therapy for decades, knowledge on HCQ as a potential treatment for COVID-19 is limited and multiple clinical trials have just emerged. Especially, rare HCQ side effects which were of minor importance for use in selected indications might gain major relevance with population-wide application. These rare side effects include retinopathy and-even more important-QT prolongation leading to sudden cardiac death by malignant arrhythmias.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Pandemias , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Retinianas/induzido quimicamente
11.
Subst Use Misuse ; 55(11): 1900-1901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32657207

RESUMO

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.


Assuntos
Analgésicos Opioides/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Infecções por Coronavirus/complicações , Hospedeiro Imunocomprometido/imunologia , Transtornos Relacionados ao Uso de Opioides/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/induzido quimicamente , Imunidade Adaptativa/imunologia , Analgésicos Opioides/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Interações Medicamentosas , Humanos , Imunidade Inata/imunologia , Metadona/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/imunologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Insuficiência Respiratória/fisiopatologia
12.
Arch Cardiol Mex ; 90(Supl): 36-40, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-595309

RESUMO

The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia
15.
Circ Heart Fail ; 13(7): e007220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32500721

RESUMO

The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.


Assuntos
Síndrome Coronariana Aguda/terapia , Arritmias Cardíacas/terapia , Infecções por Coronavirus/terapia , Insuficiência Cardíaca/terapia , Miocardite/terapia , Pneumonia Viral/terapia , Síndrome Coronariana Aguda/complicações , Antibacterianos/efeitos adversos , Antivirais/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/complicações , Azitromicina/efeitos adversos , Betacoronavirus , Cardiotônicos/uso terapêutico , Doença Crônica , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/terapia , Inibidores Enzimáticos/efeitos adversos , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/etiologia , Coração Auxiliar , Humanos , Hidroxicloroquina/efeitos adversos , Balão Intra-Aórtico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Miocardite/complicações , Pandemias , Intervenção Coronária Percutânea , Pneumonia Viral/complicações , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Tromboembolia
16.
J Cardiovasc Pharmacol Ther ; 25(6): 508-522, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32588641

RESUMO

Phytogenic cannabinoids from Cannabis sativa and synthetic cannabinoids are commonly used substances for their recreational and medicinal properties. There are increasing reports of cardiotoxicity in close temporal association with cannabinoid use in patients with structurally normal hearts and absence of coronary arterial disease. Associated adverse events include myocardial ischemia, conduction abnormalities, arrhythmias, and sudden death. This review details the effects of phytogenic and synthetic cannabinoids on diverse receptors based on evidence from in vitro, human, and animal studies to establish a molecular basis for these deleterious clinical effects. The synergism between endocannabinoid dysregulation, cannabinoid receptor, and noncannabinoid receptor binding, and impact on cellular ion flux and coronary microvascular circulation is delineated. Pharmacogenetic factors placing certain patients at higher risk for cardiotoxicity are also correlated with the diverse effects of cannabinoids.


Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Arritmias Cardíacas/induzido quimicamente , Agonistas de Receptores de Canabinoides/efeitos adversos , Canabinoides/efeitos adversos , Cannabis/efeitos adversos , Coração/efeitos dos fármacos , Abuso de Maconha/complicações , Fumar Maconha/efeitos adversos , Síndrome Coronariana Aguda/fisiopatologia , Animais , Arritmias Cardíacas/fisiopatologia , Agonistas de Receptores de Canabinoides/síntese química , Agonistas de Receptores de Canabinoides/isolamento & purificação , Canabinoides/síntese química , Canabinoides/isolamento & purificação , Cannabis/química , Cardiotoxicidade , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Receptores de Canabinoides/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Transdução de Sinais
20.
Arch Cardiol Mex ; 90(Supl): 36-40, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523150

RESUMO

The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia
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