Fig 1 - available via license: CC BY
Content may be subject to copyright.
Source publication
Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decad...
Contexts in source publication
Context 1
... is a 4-aminoquinoline known since 1934, discovered in the first half of the twentieth century as an effective substitute for quinine. Currently, CQ is the drug of choice for the treatment of malaria [12]. Hydroxychloroquine is a hydroxylated analogue of CQ that has both antimalarial and antiinflammatory activities (Fig. 1). These two molecules enter cells as non-protonated forms and become protonated, inversely proportional to pH, according to Henderson-Hasselbach's law. Therefore, these drugs are concentrated in acidic organelles, including endosomes, lysosomes and Golgi vesicles, increasing the pH ...
Context 2
... systematic review about CQ and HCQ cardiotoxicity found 86 articles, comprising only 127 patients in case reports or small case series, most of them were SLE (n = 49) or RA patients (n = 28). Most patients (58.3%) were treated with CQ with a median time of use of 7 years (3 days to 35 years) and median cumulative dose of 803 g (1235 g for HCQ). Heart rhythm problems were the main reported side effects, affecting 85% of patients. ...
Similar publications
![Figure 1: Virus breakdown by chloroquine (marked by purple arrows) [12].](profile/Nnenne-Onu/publication/342708913/figure/fig1/AS:910261246504960@1594034601286/Virus-breakdown-by-chloroquine-marked-by-purple-arrows-12_Q320.jpg)
Keywords: COVID-19; Hydroxychloroquine; Chloroquine The disease, COVID-19 has brought a lot of untold hardships to people, affecting persons from all cadres of human existence and causing a great deal of tragedy to nations. The race to halt this unseen enemy has gained momentum. This is seen in many trials, which are currently re-evaluating existin...
Citations
... thrombosis and ischemic heart disease. It has demonstrated its benefit in preventing thrombotic events in [1][2][3] APLS. Recently, HCQ use in diabetic population has resulted in clinically meaningful improvement in 4 diabetic control. ...
Background: Hydroxychloroquine (HCQ) has been historically used for treatment of autoimmune diseases and more recently, it is used for treatment of COVID-19 patients. Using HCQ in COVID-19 patients resulted in corrected QT(QTc) prolongation which has potential to deteriorate into Torsades de Pointes and sudden cardiac death. As it is used chronically by rheumatologic patients so this study was designed to establish effect of HCQ on QTc in rheumatic patients. Methods: A cross sectional comparative study conducted in Rheumatology Department Shaikh Zayed hospital, Lahore. Non-probability consecutive sampling technique was used. Duration of study was 169 days. 45 patients used HCQ for three months and 45 patients did not use HCQ. ECG was done at induction in the study and after three months. Serum calcium, potassium and magnesium were also checked at onset. QTc was calculated by Bazett’s formula. Results: QTc did not raise in 21(46%) patients, in both groups. QTc raised between 1- 50msec in 20(44.4%) and 23(51.1%) patients in HCQ exposed and unexposed patients, respectively. QTc rise more than 50msec in 4(8.88%) and 1(2.2%) patient in HCQ exposed and unexposed patients, respectively (p-value=0.344). The QTc change is associated with heart rate showing 75.0% chances of increased QTc among those with increased heart rate. Conclusion: HCQ did not increase QTc interval in 46% study. 8.88% of HCQ exposed population and 2.22% of HCQ unexposed population had significant change in QTc. However, no adverse cardiac events were observed in study duration
... This in turn results in the impairment and inhibition of various functions, including antigen presentation, prostaglandin and cytokine production, Toll-like receptor signalling, and leucocyte activation. These effects allow HCQ to play its immunosuppressive, antiproliferative, antithrombotic, and photoprotective roles [7,8]. ...
This review provides an overview of conventional and novel retinal imaging modalities for hydroxychloroquine (HCQ) retinopathy. HCQ retinopathy is a form of toxic retinopathy resulting from HCQ use for a variety of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Each imaging modality detects a different aspect of HCQ retinopathy and shows a unique complement of structural changes. Conventionally, spectral-domain optical coherence tomography (SD-OCT), which shows loss or attenuation of the outer retina and/or retinal pigment epithelium–Bruch’s membrane complex, and fundus autofluorescence (FAF), which shows parafoveal or pericentral abnormalities, are used to assess HCQ retinopathy. Additionally, several variations of OCT (retinal and choroidal thickness measurements, choroidal vascularity index, widefield OCT, en face imaging, minimum intensity analysis, and artificial intelligence techniques) and FAF techniques (quantitative FAF, near-infrared FAF, fluorescence lifetime imaging ophthalmoscopy, and widefield FAF) have been applied to assess HCQ retinopathy. Other novel retinal imaging techniques that are being studied for early detection of HCQ retinopathy include OCT angiography, multicolour imaging, adaptive optics, and retromode imaging, although further testing is required for validation.
... Although chronic use of 1 can cause significant adverse effects, such as cardiotoxicity or neurotoxicity [45], it is still widespread due to its high effectiveness in controlling plasmodium and low cost of production. Studies aimed at obtaining a more active and less toxic 1 derivative led to the discovery of hydroxychloroquine (HCQ-2, Fig. 2A) in 1950. ...
... Compound 43 was hydrolyzed in the presence of ammonia, forming diamide 44. The cyclization step between 44 and glyoxal was performed under acidic conditions, and pyrazinamide salt (45) was obtained in good yield. The bromination reaction of 45 was carried out in good flow, and compound 46 was obtained in good yield. ...
Introduction
Drug repositioning is a strategy to identify a new therapeutic indication for molecules that have been approved for other conditions, aiming to speed up the traditional drug development process and reduce its costs. The high prevalence and incidence of coronavirus disease 2019 (COVID-19) underline the importance of searching for a safe and effective treatment for the disease, and drug repositioning is the most rational strategy to achieve this goal in a short period of time. Another advantage of repositioning is the fact that these compounds already have established synthetic routes, which facilitates their production at the industrial level. However, the hope for treatment cannot allow the indiscriminate use of medicines without a scientific basis.
Results
The main small molecules in clinical trials being studied to be potentially repositioned to treat COVID-19 are chloroquine, hydroxychloroquine, ivermectin, favipiravir, colchicine, remdesivir, dexamethasone, nitazoxanide, azithromycin, camostat, methylprednisolone, and baricitinib. In the context of clinical tests, in general, they were carried out under the supervision of large consortiums with a methodology based on and recognized in the scientific community, factors that ensure the reliability of the data collected. From the synthetic perspective, compounds with less structural complexity have more simplified synthetic routes. Stereochemical complexity still represents the major challenge in the preparation of dexamethasone, ivermectin, and azithromycin, for instance.
Conclusion
Remdesivir and baricitinib were approved for the treatment of hospitalized patients with severe COVID-19. Dexamethasone and methylprednisolone should be used with caution. Hydroxychloroquine, chloroquine, ivermectin, and azithromycin are ineffective for the treatment of the disease, and the other compounds presented uncertain results. Preclinical and clinical studies should not be analyzed alone, and their methodology’s accuracy should also be considered. Regulatory agencies are responsible for analyzing the efficacy and safety of a treatment and must be respected as the competent authorities for this decision, avoiding the indiscriminate use of medicines.
... [82]. Cardiotoxicity with arrhythmias reported in the elderly with pre-existing cardiac history questioned the safety and efficacy of HCQ therapy [83]. Another trial demonstrated that hospitalized COVID-19 subjects on HCQ did not show a lower incidence of death at 28 days compared to non-HCQ subjects, confirming the lack of HCQ efficacy in COVID-19 [84]. ...
Consequences of Corona Virus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) are clinically diverse. SARS-CoV-2 infection has been associated with various autoimmune and rheumatic manifestations over the past three years. Emerging evidence points to the possibility of Long COVID predisposition in rheumatic patients due to the changes in immune regulatory response. The aim of this article was to overview data on the pathobiology of Long COVID in patients with RDs. Related risk factors, clinical characteristics, and prognosis of Long COVID in RDs were analyzed. Relevant articles were retrieved from Medline/PubMed, Scopus, and Directory of Open Access Journals (DOAJ). Diverse mechanisms of viral persistence, chronic low-grade inflammation, lasting production of autoantibodies, endotheliopathy, vascular complications, and permanent tissue damage have been described in association with Long COVID. Patients with RDs who survive COVID-19 often experience severe complications due to the immune disbalance resulting in multiple organ damage. Regular monitoring and treatment are warranted in view of the accumulating evidence.
... (2) Interference of cyclic GMP/AMP synthase, an essential enzyme in the function of type I interferon and IL-1. (3) Inhibition of Phospholipase A2 (PLA2) [7]. (4) Downregulation of the synthesis of proinflammatory cytokines, such as IL-1, IL-6, TNF, and IFN-γ in T and B cells [6]. ...
... Other benefits include a reduced risk of thromboembolism in patients with antiphospholipid antibodies [9], better glycemic control in SLE patients, and improved insulin sensitivity, thus decreasing the risk of developing diabetes [21,22]. The use of antimalarials leads to improved lipid profiles through reduced cholesterol synthesis and LDL receptor activity [7,22,23], improved bone density [24], and lower cancer risk [25]. ...
... HCQ and CQ have an established good safety profile and are usually well tolerated [7]. They are considered immunomodulatory, but not immunosuppressive, because their usage is not associated with an increased risk of infection or cancer [1]. ...
The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may compromise adherence and response to treatment. Therapy selection and monitoring will depend on patient characteristics and the safety profile of each drug. The aim of this review is to provide a comprehensive understanding of the most important synthetic drugs used in the treatment of SLE, including the current treatment options (mycophenolate mofetil, azathioprine, and cyclophosphamide), review their mechanism of action, efficacy, safety, and, most importantly, provide monitoring parameters that should be considered while the patient is receiving the pharmacotherapy.
... In addition, methotrexate appears to have cardioprotective properties on lipids and endothelium, in contrast to patients receiving adalimumab (53). Similarly, Hydroxychloroquine (HCQ) was found to have a protective effect on the vascular endothelium of RA patients (54), and it causes a lower cardiovascular risk in RA patients (55,56). HCQ treatment can reduce low-density lipoprotein and Triglyceride serum values, and plays an anti-platelet aggregation role, thus it is considered to be cardioprotective (57).Tumor necrosis factor inhibitor (TNFi) therapy in RA reduces CVD risk via inhibition of endothelial dysfunction and slows the progression of atherosclerosis by reducing the expression of proinflammatory cytokines and endothelial adhesion molecules (58). ...
As a systemic autoimmune disease, rheumatoid arthritis (RA) usually causes damage not only to joints, but also to other tissues and organs including the heart, kidneys, lungs, digestive system, eyes, skin, and nervous system. Excessive complications are closely related to the prognosis of RA patients and even lead to increased mortality. This article summarizes the serious complications of RA, focusing on its incidence, pathogenesis, clinical features, and treatment methods, aiming to provide a reference for clinicians to better manage the complications of RA.
... Hydroxychloroquine (HCQ) is initially used as an antimalarial drug, and is now widely used to treat many rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) (1)(2)(3)(4)(5). In particular condition, HCQ is used for the therapy of primary Sjögren's syndrome (pSS) (6) and antiphospholipid syndrome (APS) (7). ...
... In addition, HCQ blocks activation of endosomal TLRs by directly interacting with nucleic acids and preventing their binding to endosomal TLRs, thus inhibiting subsequent signal transduction pathway (8)(9)(10). HCQ reduces disease activity, flaring up, organ damage, steroid dose and mortality in SLE patients (4,11,12). It also improves disease activity and functional ability in RA patients (13). ...
Objectives:
To investigate the association of hydroxychloroquine (HCQ) with the risk of cardiovascular disease (CVD) events in patients with traditional risk factors, hypertension (HTN) or diabetes mellitus (DM).
Methods:
We conducted a retrospective cohort study from 1 January, 2010 to 30 September, 2022. There was a total of 1007585 patients from a hospital-based population. In this cohort, 146862 patients had newly diagnosed HTN or DM. Among these patients, 1903 patients had HCQ exposure and 136396 patients had no HCQ exposure after exclusion of previous CVD events or invasive cardiovascular procedures. The risk of developing CVD events, a composite of acute myocardial infarction (AMI) and ischaemic stroke was evaluated.
Results:
The patients with HCQ exposure had reduced risk of CVD events [HR (hazard ratio)=0.67 95%CI: 0.55-0.83], AMI (HR=0.61, 95%CI: 0.41-0.90) and ischaemic stroke (HR=0.74, 95%CI:0.59-0.93), when compared with non-HCQ exposure, after adjusting for age, sex, rheumatic diseases, comorbidities and medications. Specifically, reduced risk for CVD events (HR=0.67, 95%CI: 0.54-0.83), including AMI (HR=0.67, 95%CI: 0.44-1.00) and ischaemic stroke (HR=0.71, 95%CI: 0.55-0.90) were observed in older patients (age ≥50 yrs) with HCQ exposure, and reduced risk for AMI also observed in younger patients (age <50 yrs) (HR=0.28, 95%CI: 0.08-0.97). Reduced risk for CVD events (HR=0.63, 95%CI: 0.48-0.82) and ischaemic stroke (HR=0.63, 95%CI: 0.47-0.85) were observed particularly in female patients with HCQ exposure. Reduced risk for AMI was observed particularly in male patients with HCQ exposure (HR=0.44, 95%CI: 0.22-0.87).
Conclusions:
HCQ has protective effect on CVD events, including both AMI and ischaemic stroke in the patients with traditional risk factors. The protective effect of HCQ on CVD events is prominent in older patients.
... It is likely that due to the chronic progressive nature of fibrotic change, fibrosis may not play an important part in the proarrhythmic mechanisms of anti-malarial drugs in the acute setting. However, this becomes important when anti-malarial drugs are repurposed for other conditions such as rheumatoid arthritis requiring longer term regimens of the drug (Dos Reis Neto et al., 2020). Additionally, these mechanisms are relevant during chloroquine administration in patients under high-oxidative stress conditions, such as pathological myocardial hypertrophy or heart failure (Chaanine et al., 2015;Zhang et al., 2020). ...
Malaria remains the leading cause of parasitic death in the world. Artemisinin resistance is an emerging threat indicating an imminent need for novel combination therapy. Given the key role of mass drug administration, it is pivotal that the safety of anti‐malarial drugs is investigated thoroughly prior to widespread use. Cardiotoxicity, most prominently arrhythmic risk, has been a concern for anti‐malarial drugs. We clarify the likely underlying mechanisms by which anti‐malarial drugs predispose to arrhythmias. These relate to disruption of (1) action potential upstroke due to effects on the sodium currents, (2) action potential repolarisation due to effects on the potassium currents, (3) cellular calcium homeostasis, (4) mitochondrial function and reactive oxygen species production and (5) cardiac fibrosis. Together, these alterations promote arrhythmic triggers and substrates. Understanding these mechanisms is essential to assess the safety of these drugs, stratify patients based on arrhythmic risk and guide future anti‐malarial drug development.
... Следовательно, он может снизить иммунитет пациентов и, следовательно, усилить рост грибков [16]. Кроме того, длительное применение антибиотиков широкого спектра действия может привести к устранению конкурентного влияния нормальной бактериальной флоры, что приводит к чрезмерному росту грибов [17]. ...
Introduction. COVID-19 is widely known as a disease that causes respiratory dysfunction, however, it is also associated with a mass of extrapulmonary manifestations and complications, gastrointestinal, hepatocellular complications, neurological diseases, as well as complications in the maxillofacial region. Aim. The aim of this study was to diagnose osteomyelitis of the upper jaw in post COVID-19 patients using multispiral computed tomography. Material and methods. We retrospectively evaluated radiation imaging and clinical data of 37 patients, aged 28 to 52 years with osteomyelitis of the upper jaw, who underwent COVID-19. The male sex prevailed among the patients. Results and discussion. All patients had sinusitis and ophthalmic symptoms. The pattern of anatomical lesions of the upper jaw, nasal cavity, maxillary sinus, orbit, and lattice cells was consistently observed in all patients. Conclusion. Progressive and rapid course, involvement of the cavernous sinus, vascular structures, and further upward spread (intracranial) complications may be the usual evolution of rhinophthalmocerebral mucormycosis. Multiplanar tomographic imaging shows the localization, nature, as well as relationship of the surrounding structures, helping in turn to plan the operation. However, the prognosis remains difficult, despite radical surgery and, in particular, antifungal treatment.
... HCQ improves aAnA5 expression [163], reduces aPL binding to syncytiotrophoblasts [164], shows anti-platelet action [165] and decreases inflammation through its action on TNF-α and exerts a complement pathway inhibition [166]. It has been reported that HCQ is safe during pregnancy and breastfeeding [167]; thus, serious side effects associated with HCQ exposure are scarce; even the EULAR has permitted its use for OAPS treatment [22]. ...
Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS.
