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1.
Scand J Trauma Resusc Emerg Med ; 29(1): 48, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33722251

RESUMEN

BACKGROUND: Chloroquine use has increased worldwide recently in the setting of experimental treatment for the novel coronavirus disease (Covid-19). Nevertheless, in case of chloroquine intoxication, it can be life threatening, with cardiac arrest, due to its cardiac toxicity. CASE PRESENTATION: This case study reports on a 14-years-old girl who presented in cardiac arrest after an uncommon suicide attempt by ingesting 3 g of chloroquine. After 66 min of cardio-pulmonary resuscitation (CPR), extracorporeal cardiopulmonary resuscitation (ECPR) was initiated, allowing cardiac function to recover. CONCLUSIONS: Chloroquine intoxication is a rare but serious condition due to its cardiac toxicity. Use of ECPR in this case of transient toxicity allowed a favorable evolution with little neurological impairment.


Asunto(s)
/tratamiento farmacológico , Reanimación Cardiopulmonar/métodos , Cloroquina/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Paro Cardíaco/terapia , Adolescente , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Femenino , Paro Cardíaco/inducido químicamente , Humanos , Pandemias , Índice de Severidad de la Enfermedad
2.
Biomed Res Int ; 2021: 8821318, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732744

RESUMEN

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.


Asunto(s)
/tratamiento farmacológico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
3.
Cochrane Database Syst Rev ; 3: CD007478, 2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33687069

RESUMEN

BACKGROUND: Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits. OBJECTIVES: To assess the effects of interventions for cutaneous disease in SLE. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence. MAIN RESULTS: Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate. AUTHORS' CONCLUSIONS: Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.


Asunto(s)
Fármacos Dermatológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/terapia , Enfermedades de la Piel/terapia , Edad de Inicio , Azatioprina/uso terapéutico , Sesgo , Factores Biológicos/uso terapéutico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Técnicas Cosméticas , Ciclosporina/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Exantema , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Cutáneo/clasificación , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/terapia , Lupus Eritematoso Sistémico/clasificación , Lupus Eritematoso Sistémico/complicaciones , Masculino , Medicina China Tradicional , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Placebos/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades de la Piel/etiología , Brote de los Síntomas
4.
Ann Agric Environ Med ; 28(1): 122-126, 2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33775077

RESUMEN

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic causes vital concerns due to the lack of proved, effective, and safe therapy. Chloroquine and hydroxychloroquine seem to be useful, but recently serious concerns regarding their adverse events have risen. The aim of the study was to broaden the general perspective of chloroquine and hydroxychloroquine use in COVID-19 treatment, based on an analysis of their current safety profile among patients with rheumatic diseases. MATERIAL AND METHODS: The study was based on a group of 152 patients with rheumatic diseases, aged 20-78 years, treated either with chloroquine or hydroxychloroquine. Analyzed data included age, gender, comorbidities, type of drug, dosage, treatment duration, and reported adverse events. Cases of drug withdrawal related to adverse events were also recorded. RESULTS: The dosage was consistent in both groups: 250 mg of chloroquine or 200 mg of hydroxychloroquine daily. 77.6% of patients did not experience any adverse reactions to the treatment. Hydroxychloroquine showed better safety profile, with 10.9% of patients reporting side-ffects, compared to 28.9% in patients treated with chloroquine. The overall incidence of ophthalmic complications was 6.6%. For both drugs, no statistically significant correlation between adverse events and age, chronic heart or liver disease, or hypertension was found. CONCLUSIONS: Chloroquine and hydroxychloroquine at lower doses, as used in rheumatic diseases, prove to be relatively safe. Data from the literature show that high dosage as recommended in COVID-19 treatment may pose a risk of toxicity and require precise management, but prophylactic, long-term use of lower, safe doses might be a promising solution.


Asunto(s)
Antirreumáticos/efectos adversos , Cloroquina/efectos adversos , Hidroxicloroquina/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológico , Adulto , Anciano , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Cloroquina/administración & dosificación , Cloroquina/uso terapéutico , Ojo/efectos de los fármacos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Masculino , Persona de Mediana Edad
5.
Can Fam Physician ; 67(3): 171-179, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33727376

RESUMEN

OBJECTIVE: To keep health care providers, in response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, informed about the medications that have been proposed to treat the disease and the evidence supporting their use. QUALITY OF EVIDENCE: A narrative review of medications most widely used to treat COVID-19 was conducted, outlining the best available evidence for each pharmacologic treatment to date. Searches were performed in PubMed, EMBASE, and MEDLINE using key words COVID-19 and treatment, as well as related terms. Relevant research studies conducted in human populations and cases specific to patients with COVID-19 were included, as were relevant hand-searched papers and reviews. Only articles in English and Chinese were included. MAIN MESSAGE: While current management of patients with COVID-19 largely involves supportive care, without a widely available vaccine, practitioners have also resorted to repurposing medications used for other indications. This has caused considerable controversy, as many of these treatments have limited clinical evidence supporting their use and therefore pose implications for patient safety, drug access, and public health. For instance, medications such as hydroxychloroquine and chloroquine, lopinavir-ritonavir, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers gained widespread media attention owing to hype, misinformation, or misinterpretation of research evidence. CONCLUSION: Given the severity of the pandemic and the potential broad effects of implementing safe and effective treatment, this article provides a narrative review of the current evidence behind the most widely used medications to treat COVID-19 in order to enable health care practitioners to make informed decisions in the care of patients with this life-threatening disease.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antivirales/uso terapéutico , Medicina Basada en la Evidencia , Inmunoglobulinas/uso terapéutico , Cloroquina/uso terapéutico , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapéutico
6.
BMC Med Res Methodol ; 21(1): 42, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637044

RESUMEN

BACKGROUND: The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set forth as an early response to the COVID-19 pandemic. METHODS: First, we reviewed all registered clinical trials on COVID-19. The World Health Organization International Trials Registry Platform and national trial registries were searched for COVID-19 trials through April 19th, 2020. For each record, independent researchers extracted interventions, participants, and methodological characteristics. Second, on September 14th, 2020 we evaluated the recruitment status and availability of the results of COVID-19 treatment trials previously identified. RESULTS: In April 2020, a total of 580 trials evaluating COVID-19 treatment were registered. Reporting quality was poor (core participant information was missing in 24.1 to 92.7%). Between 54.0 and 93.8% of the trials did not plan to include older people or those with a higher baseline risk. Most studies were randomised (67.9%), single-centre (58.3%), non-industry-funded (81.1%), to be conducted in China (47.6%), with a median duration of 184 days and a median sample size of 100 participants. Core endpoints (mortality, clinical status, and hospitalization length) were planned to be assessed in 5.2 to 13.1% of the trials. Five months later, 66 trials (11.4%) were reported as "Completed", and only 46 (7.9%) had public results available. One hundred forty-four of 580 trials (24.8%) either had the status "Not yet recruiting" or "Suspended", and 18 (3.1%) trials were prematurely stopped ("Terminated" or "Withdrawn") The number of completed trials and trials with results are much lower than anticipated, considering the planned follow-up. CONCLUSIONS: Our results raise concerns about the success of the initial global research effort on COVID-19 treatment. The clinical and methodological characteristics of early COVID-19 treatment trials limit their capability to produce clear answers to critical questions in the shortest possible time.


Asunto(s)
/tratamiento farmacológico , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , /efectos de los fármacos , Corticoesteroides/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antivirales/uso terapéutico , /virología , Cloroquina/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pandemias , /fisiología
7.
Rev Esp Quimioter ; 34(2): 145-150, 2021 Apr.
Artículo en Español | MEDLINE | ID: mdl-33522213

RESUMEN

OBJECTIVE: Despite the impact of SARS-CoV-2 infection in geriatrics, data on nonagenarian patients is scarce. The aim of this study is to describe the clinical features of COVID19-diagnosed nonagenarians, as well as its clinical evolution and therapeutic response. METHODS: Retrospective observational study of nonagenarians, admitted for COVID-19. Sociodemographic and clinical variables were registered, including previous polypharmacy. Blood analysis data and COVID-19-specific treatment were registered. RESULTS: A total of 79 patients were included, with 50.6% (40 patients) of mortality. None of the comorbidities registered correlated with mortality, which was significantly higher among patients with moderate/complete functional dependence, compared to those mild-dependents/independents (59.5% vs 40.5%; p=0.015). Most prescribed drugs were hydroxychloroquine/chloroquine and azithromycin. Non-survivors presented higher counts of leukocytes and neutrophils, and higher lymphopenia. CONCLUSIONS: Nonagenarians with functional dependence presented higher mortality, irrespective of comorbidities or treatment received. Implementing an integral geriatric evaluation would enhance the implementation of personalized therapeutic strategies for nonagenarians.


Asunto(s)
Anciano de 80 o más Años , /mortalidad , Hospitalización , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Cloroquina/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Rendimiento Físico Funcional , Polifarmacia , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
8.
Molecules ; 26(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525415

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 × 10-3 to 5.47 × 10-6 for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.


Asunto(s)
Cloroquina/química , Hidroxicloroquina/química , Simulación del Acoplamiento Molecular , Polimorfismo Genético , Glicoproteína de la Espiga del Coronavirus , /química , /metabolismo , /metabolismo , Cloroquina/farmacocinética , Cloroquina/uso terapéutico , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapéutico , Dominios Proteicos , /metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo
9.
Cochrane Database Syst Rev ; 2: CD013587, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33624299

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. OBJECTIVES: To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID-19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS-CoV-2 exposure; 3) preventing infection in people exposed to SARS-CoV-2. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled-trials.com), and the COVID-19-specific resources www.covid-nma.com and covid-19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID-19, people at risk of COVID-19 exposure, and people exposed to COVID-19. Adverse events (any, serious, and QT-interval prolongation on electrocardiogram) were also extracted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane 'Risk of bias' tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta-analysis using a random-effects model for outcomes where pooling of effect estimates was appropriate. MAIN RESULTS: 1. Treatment of COVID-19 disease We included 12 trials involving 8569 participants, all of whom were adults. Studies were from China (4); Brazil, Egypt, Iran, Spain, Taiwan, the UK, and North America (each 1 study); and a global study in 30 countries (1 study). Nine were in hospitalized patients, and three from ambulatory care. Disease severity, prevalence of comorbidities, and use of co-interventions varied substantially between trials. We found potential risks of bias across all domains for several trials. Nine trials compared HCQ with standard care (7779 participants), and one compared HCQ with placebo (491 participants); dosing schedules varied. HCQ makes little or no difference to death due to any cause (RR 1.09, 95% CI 0.99 to 1.19; 8208 participants; 9 trials; high-certainty evidence). A sensitivity analysis using modified intention-to-treat results from three trials did not influence the pooled effect estimate.  HCQ may make little or no difference to the proportion of people having negative PCR for SARS-CoV-2 on respiratory samples at day 14 from enrolment (RR 1.00, 95% CI 0.91 to 1.10; 213 participants; 3 trials; low-certainty evidence). HCQ probably results in little to no difference in progression to mechanical ventilation (RR 1.11, 95% CI 0.91 to 1.37; 4521 participants; 3 trials; moderate-certainty evidence). HCQ probably results in an almost three-fold increased risk of adverse events (RR 2.90, 95% CI 1.49 to 5.64; 1394 participants; 6 trials; moderate-certainty evidence), but may make little or no difference to the risk of serious adverse events (RR 0.82, 95% CI 0.37 to 1.79; 1004 participants; 6 trials; low-certainty evidence). We are very uncertain about the effect of HCQ on time to clinical improvement or risk of prolongation of QT-interval on electrocardiogram (very low-certainty evidence). One trial (22 participants) randomized patients to CQ versus lopinavir/ritonavir, a drug with unknown efficacy against SARS-CoV-2, and did not report any difference for clinical recovery or adverse events. One trial compared HCQ combined with azithromycin against standard care (444 participants). This trial did not detect a difference in death, requirement for mechanical ventilation, length of hospital admission, or serious adverse events. A higher risk of adverse events was reported in the HCQ-and-azithromycin arm; this included QT-interval prolongation, when measured. One trial compared HCQ with febuxostat, another drug with unknown efficacy against SARS-CoV-2 (60 participants). There was no difference detected in risk of hospitalization or change in computed tomography (CT) scan appearance of the lungs; no deaths were reported. 2. Preventing COVID-19 disease in people at risk of exposure to SARS-CoV-2 Ongoing trials are yet to report results for this objective. 3. Preventing COVID-19 disease in people who have been exposed to SARS-CoV-2 One trial (821 participants) compared HCQ with placebo as a prophylactic agent in the USA (around 90% of participants) and Canada. Asymptomatic adults (66% healthcare workers; mean age 40 years; 73% without comorbidity) with a history of exposure to people with confirmed COVID-19 were recruited. We are very uncertain about the effect of HCQ on the primary outcomes, for which few events were reported: 20/821 (2.4%) developed confirmed COVID-19 at 14 days from enrolment, and 2/821 (0.2%) were hospitalized due to COVID-19 (very low-certainty evidence). HCQ probably increases the risk of adverse events compared with placebo (RR 2.39, 95% CI 1.83 to 3.11; 700 participants; 1 trial; moderate-certainty evidence). HCQ may result in little or no difference in serious adverse events (no RR: no participants experienced serious adverse events; low-certainty evidence). One cluster-randomized trial (2525 participants) compared HCQ with standard care for the prevention of COVID-19 in people with a history of exposure to SARS-CoV-2 in Spain. Most participants were working or residing in nursing homes; mean age was 49 years. There was no difference in the risk of symptomatic confirmed COVID-19 or production of antibodies to SARS-CoV-2 between the two study arms. AUTHORS' CONCLUSIONS: HCQ for people infected with COVID-19 has little or no effect on the risk of death and probably no effect on progression to mechanical ventilation. Adverse events are tripled compared to placebo, but very few serious adverse events were found. No further trials of hydroxychloroquine or chloroquine for treatment should be carried out. These results make it less likely that the drug is effective in protecting people from infection, although this is not excluded entirely. It is probably sensible to complete trials examining prevention of infection, and ensure these are carried out to a high standard to provide unambiguous results.


Asunto(s)
Antimaláricos/uso terapéutico , /prevención & control , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Adulto , Anciano , Antimaláricos/efectos adversos , Antivirales/efectos adversos , Antivirales/uso terapéutico , Sesgo , /mortalidad , Causas de Muerte , Cloroquina/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Persona de Mediana Edad , Pandemias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos , Nivel de Atención , Resultado del Tratamiento
11.
Eur J Pharmacol ; 897: 173928, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33545161

RESUMEN

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate certain pathways that can potentially be exploited for therapeutic gain. For example, in the airways, this has opened an attractive avenue for developing novel bitter taste ligands as a new class of bronchodilators for asthma. While CQ and its derivatives have been proposed as a therapy in COVID-19, it remains to be seen whether it really work in the clinic? To this end, our perspective aims to provide a timely yet brief insights on the existing literature on CQ and the controversies surrounding its use in COVID-19. Further, we also highlight some of cell-based mechanism(s) that CQ and its derivatives affect in mediating variety of physiological responses in the cell. We believe, data emanating from the clinical studies and continual understanding of the fundamental mechanisms may potentially help in designing effective therapeutic strategies that meets both efficacy and safety criteria for COVID-19.


Asunto(s)
Antimaláricos/uso terapéutico , Autofagia/efectos de los fármacos , Cloroquina/uso terapéutico , Gusto/efectos de los fármacos , Reposicionamiento de Medicamentos , Humanos
12.
Pharmacol Res Perspect ; 9(1): e00705, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33421347

RESUMEN

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.


Asunto(s)
Antivirales/uso terapéutico , /tratamiento farmacológico , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Cloroquina/uso terapéutico , Interacciones Farmacológicas , Humanos , Lopinavir/uso terapéutico , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico
13.
Toxicol Appl Pharmacol ; 414: 115412, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33484708

RESUMEN

COVID-19 is a pandemic with no end in sight. There is only one approved antiviral agent but global stocks are deemed insufficient. Despite in vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were disappointing, and they may even impair outcomes. Chloroquine causes zebroid deposits reminiscent of Fabry disease (α-galactosidase A deficiency) and endothelial cells are key targets of COVID-19. We have explored the effect of chloroquine on cultured endothelial cells and its modulation by recombinant α-galactosidase A (agalsidase). Following dose-response studies, 0.5 µg/mL chloroquine was added to cultured human endothelial cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) - MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro test concentrations for COVID-19 therapy. At a sublethal concentration, chloroquine significantly induced the accumulation of acid organelles (P < 0.05), increased ROS levels, and decreased NO production (P < 0.05). These adverse effects of chloroquine on endothelial cell biology were decreased by agalsidase-ß (P < 0.05). Chloroquine-induced endothelial cell cytotoxicity and stress is attenuated by agalsidase-ß treatment. This suggests that endothelial cell injury may contribute to the failure of chloroquine as therapy for COVID-19 and may be at least in part related to causing dysfunction of the lysosomal enzyme α-galactosidase A.


Asunto(s)
/tratamiento farmacológico , Cloroquina/efectos adversos , Células Endoteliales/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Lisosomas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cloroquina/administración & dosificación , Cloroquina/uso terapéutico , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Enfermedad de Fabry/inducido químicamente , Humanos , Pandemias , Especies Reactivas de Oxígeno
14.
Appl Microbiol Biotechnol ; 105(4): 1333-1343, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33515285

RESUMEN

The anti-malarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been suggested as promising agents against the new coronavirus SARS-CoV-2 that induces COVID-19 and as a possible therapy for shortening the duration of the viral disease. The antiviral effects of CQ and HCQ have been demonstrated in vitro due to their ability to block viruses like coronavirus SARS in cell culture. CQ and HCQ have been proposed to reduce immune reactions to infectious agents, inhibit pneumonia exacerbation, and improve lung imaging investigations. CQ analogs have also revealed the anti-inflammatory and immunomodulatory effects in treating viral infections and related ailments. There was, moreover, convincing evidence from early trials in China about the efficacy of CQ and HCQ in the anti-COVID-19 procedure. Since then, research and studies have been massive to ascertain these drugs' efficacy and safety in treating the viral disease. In the present review, we construct a synopsis of the main properties and current data concerning the metabolism of CQ/HCQ, which were the basis of assessing their potential therapeutic roles against the new coronavirus infection. The effective role of QC and HCQ in the prophylaxis and therapy of COVID-19 infection is discussed in light of the latest international medical-scientific research results. KEY POINTS: • Data concerning metabolism and properties of CQ/HCQ are discussed. • The efficacy of CQ/HCQ against COVID-19 has been the subject of contradictory results. • CQ/HCQ has little or no effect in reducing mortality in SARS-CoV-2-affected patients.


Asunto(s)
Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Antimaláricos/química , Antivirales/química , Cloroquina/química , Humanos , Hidroxicloroquina/química
15.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33440983

RESUMEN

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Asunto(s)
Antivirales/uso terapéutico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/farmacología , Alanina/uso terapéutico , Amidas/farmacología , Amidas/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , Cloroquina/farmacología , Cloroquina/uso terapéutico , Combinación de Medicamentos , Humanos , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/farmacología , Indoles/uso terapéutico , Interferones/farmacología , Interferones/uso terapéutico , Ivermectina/farmacología , Ivermectina/uso terapéutico , Lopinavir/farmacología , Lopinavir/uso terapéutico , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Purinas/farmacología , Purinas/uso terapéutico , Pirazinas/farmacología , Pirazinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Ribavirina/farmacología , Ribavirina/uso terapéutico , Ritonavir/farmacología , Ritonavir/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Tiazoles/farmacología , Tiazoles/uso terapéutico
16.
Arch Virol ; 166(3): 949-954, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33492523

RESUMEN

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.


Asunto(s)
Amidas/uso terapéutico , Antivirales/uso terapéutico , Pirazinas/uso terapéutico , /efectos de los fármacos , Adulto , Cloroquina/uso terapéutico , Femenino , Humanos , Tiempo de Internación , Masculino , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
18.
J Antimicrob Chemother ; 76(1): 30-42, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33031488

RESUMEN

OBJECTIVES: Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. METHODS: We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. RESULTS: Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00-1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. CONCLUSIONS: Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19.


Asunto(s)
Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Azitromicina/uso terapéutico , Cloroquina/efectos adversos , Hospitalización/estadística & datos numéricos , Humanos , Hidroxicloroquina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
Eur J Pharmacol ; 893: 173813, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33345848

RESUMEN

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an enormous challenge to the medical system, especially the lack of safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials that attracted great attention. Clinically, however, many drugs, including those currently used in COVID-19, such as chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channels, especially hERG channel through their off-target effects. The blocking of the hERG channel prolongs QT intervals on electrocardiograms; thus, it might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG channels to cause arrhythmias cannot be ignored. To develop safer and more effective drugs, it is necessary to understand the interactions between drugs and the hERG channel and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of drug-related blockade of the hERG channel to provide insights into QT prolongation caused by off-label use of related drugs in COVID-19, and hope to weigh the risks and benefits when using these drugs.


Asunto(s)
Azitromicina/efectos adversos , Azitromicina/uso terapéutico , /tratamiento farmacológico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Canal de Potasio ERG1/efectos de los fármacos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/inducido químicamente , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Combinación de Medicamentos , Humanos , Síndrome de QT Prolongado/epidemiología , Uso Fuera de lo Indicado
20.
Actas dermo-sifiliogr. (Ed. impr.) ; 112: 0-0, 2021. ilus, tab
Artículo en Inglés | IBECS | ID: ibc-196953

RESUMEN

Researchers the world over are working to find the treatments needed to reduce the negative effects of coronavirus disease 2019 (COVID-19) and improve the current prognosis of patients. Several drugs that are often used in dermatology are among the potentially useful treatments: ivermectin, antiandrogenic agents, melatonin, and the antimalarial drugs chloroquine and hydroxychloroquine. These and other agents, some of which have proven controversial, are being scrutinized by the scientific community. We briefly review the aforementioned dermatologic drugs and describe the most recent findings relevant to their use against COVID-19


Frente a la necesidad de encontrar una alternativa terapéutica que logre disminuir el impacto negativo de la COVID-19 y mejore el pronóstico actual de los pacientes, investigadores de todo el mundo se esfuerzan por aportar información que nos acerque a esta meta. Dentro de los potenciales farmacos, existen algunos de uso frecuente en dermatología: los antipalúdicos (cloroquina e hidroxicloroquina), la ivermectina, los antiandrógenos y la melatonina. Tanto estos como otros tratamientos se encuentran en la mira de la comunidad científica, siendo algunos foco de polémica y controversia. En el presente trabajo relizamos una revisión breve de los fármacos previamente mencionados, presentando los más recientes hallazgos en relación a su uso en la COVID-19


Asunto(s)
Humanos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Pandemias , Antimaláricos/uso terapéutico , Antiparasitarios/uso terapéutico , Antagonistas de Andrógenos/uso terapéutico , Cloroquina/uso terapéutico , Ivermectina/uso terapéutico , Melatonina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Antimaláricos/historia , Antimaláricos/farmacología , Antiparasitarios/historia , Antiparasitarios/farmacología , Antagonistas de Andrógenos/historia , Antagonistas de Andrógenos/farmacología , Cloroquina/historia , Cloroquina/farmacología , Ivermectina/historia , Ivermectina/farmacología , Melatonina/historia , Melatonina/farmacología , Hidroxicloroquina/historia , Hidroxicloroquina/farmacología
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