Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine

doi:10.1016/j.ijcard.2007.04.055

International Journal of Cardiology

Volume 127, Issue 2, 4 July 2008, Pages e80-e82

https://doi.org/10.1016/j.ijcard.2007.04.055 Get rights and content

Abstract

A patient with polymorphic ventricular tachycardia, long QT interval and conduction disorders secondary to long-term treatment with chloroquine is presented.

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Y.G. Yap et al.
Drug induced QT prolongation and torsades de pointes
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J.-.P. Baguet et al.
Chloroquine cardiomyopathy with conduction disorders
Heart
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There are more references available in the full text version of this article.

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This chapter explores the potential for antimicrobial drugs to cause QT interval prolongation and torsades de pointes (TdP). Common mechanisms include inhibition of the rapid component of the delayed rectifier potassium current (I_Kr) as well as pharmacokinetic and pharmacodynamic drug-drug interactions. Many antimicrobials agents have the potential to cause TdP and electrocardiogram (ECG) monitoring is recommended in some cases. Attention should also be paid to other risk factors for proarrhythmia.
Possible mechanisms behind the anti-viral effects of chloroquine and hydroxychloroquine–Which reality for the treatment of COVID-19?
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La chloroquine (CQ) et l’hydroxychloroquine (HCQ) sont connues pour inhiber l'acidification du lysosome et empêcher la fusion de vésicules endocytiques. Cette inhibition de la fusion est probablement susceptible d'interférer avec le trafic endocytaire, provoquant un scénario d'"embouteillage" qui bloquerait le transport efficace du SARS-CoV-2 dans la cellule hôte. De plus, la caractérisation de CQ/HCQ en tant qu'inhibiteurs de l'endocytose à large spectre semble associée à un mécanisme de modulation du taux d'expression du phosphatidylinositol (PICALM). En dépit de la mise à disposition d'au moins cinq vaccins anti-Covid-19 désormais largement employés ; comprendre les mécanismes possiblement impliqués dans les effets anti-viraux de la CQ et l’HCQ sont d'un grand intérêt, car leur connaissance pourrait aider à identifier si les doses utilisées lors des essais cliniques jusqu'à présent ont assuré un rapport risques/bénéfices optimal. Cette thérapie CQ/HCQ doit suivre un algorithme précis destiné à réduire les effets indésirables liés aux médications.
Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), are known to prevent acidification of lysosomes, resulting in the inhibition of endocytic vesicle fusion. Prevention of lysosome fusion is likely to interfere with endocytic trafficking, causing a "bottleneck" scenario that might block efficient transport of SARS-CoV-2 to and from the host cell membrane. Besides, the characterization of both CQ and HCQ as broad-spectrum inhibitors of endocytosis might be associated with an expression rate modulation mechanism. Despite the availability of at least five Covid-19 vaccines that are now widely used; understanding the mechanisms possibly involved in the anti-viral effects of CQ and HCQ is of great interest, as knowledge of them could help identify whether the doses used in clinical trials to date have provided an optimal risk/benefit ratio. This CQ/HCQ therapy must follow a precise algorithm designed to reduce medication-related adverse effects.
New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2
2021, Bioorganic Chemistry
Citation Excerpt :
Several drugs that were considered for repurposing to control the COVID-19 pandemic include chloroquine (CQ) and hydroxychloroquine (HCQ) (Fig. 1). These exhibited promising responses accompanied with serious side effects (ventricular arrhythmias, retinopathy, QT prolongation, or cardiac-related toxicity) [5–11]. Recently, a few quinolone-based small molecules reported their antiviral properties against SARS-CoV-2 [12–20].
At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.
Potential Drug Interactions of Repurposed COVID-19 Drugs with Lung Cancer Pharmacotherapies
2021, Archives of Medical Research
Lung cancer patients are at heightened risk for developing COVID-19 infection as well as complications due to multiple risk factors such as underlying malignancy, anti-cancer treatment induced immunosuppression, additional comorbidities and history of smoking. Recent literatures have reported a significant proportion of lung cancer patients coinfected with COVID-19. Chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, oseltamivir, remdesivir, favipiravir, and umifenovir represent the major repurposed drugs used as potential experimental agents for COVID-19 whereas azithromycin, dexamethasone, tocilizumab, sarilumab, famotidine and ceftriaxone are some of the supporting agents that are under investigation for COVID-19 management. The rationale of this review is to identify potential drug-drug interactions (DDIs) occurring in lung cancer patients receiving lung cancer medications and repurposed COVID-19 drugs using Micromedex and additional literatures. This review has identified several potential DDIs that could occur with the concomitant treatments of COVID-19 repurposed drugs and lung cancer medications. This information may be utilized by the healthcare professionals for screening and identifying potential DDIs with adverse outcomes, based on their severity and documentation levels and consequently design prophylactic and management strategies for their prevention. Identification, reporting and management of DDIs and dissemination of related information should be a major consideration in the delivery of lung cancer care during this ongoing COVID-19 pandemic for better patient outcomes and updating guidelines for safer prescribing practices in this coinfected condition.
The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2
2021, European Journal of Medicinal Chemistry
Citation Excerpt :
Both hydroxychloroquine (2) receiving patients (811) and patients with no given drug (placebo group) showed a comparable risk from intubation or death [63]. Additionally, hydroxychloroquine (2) and chloroquine (1) are known to cause several side effects, including ventricular arrhythmias, QT prolongation, retinopathy, and other cardiac-related toxicity in patients [64–66]. In June 2020, the FDA revoked the emergency authorization for hydroxychloroquine (2) and chloroquine (1) as a treatment for COVID-19, and the WHO decided to suspend the SOLIDARITY trial of hydroxychloroquine (2) [67,68].
The unforeseen emergence of coronavirus disease 2019 (COVID-19), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Wuhan province of China in December 2019, subsequently its abrupt spread across the world has severely affected human life. In a short span of time, COVID-19 has sacked more than one million human lives and marked as a severe global pandemic, which is drastically accountable for the adverse effect directly to the human society, particularly the health care system and the economy. The unavailability of approved and effective drugs or vaccines against COVID-19 further created conditions more adverse and terrifying. To win the war against this pandemic within time there is a desperate need for the most adequate therapeutic treatment, which can be achieved by the collaborative research work among scientists worldwide. In continuation of our efforts to support the scientific community, a review has been presented which discusses the structure and the activity of numerous molecules exhibiting promising SARS-CoV-2 and other CoVs inhibition activities. Furthermore, this review offers an overview of the structure, a plausible mechanism of action of SARS-CoV-2, and crucial structural features substantial to inhibit the primary virus-based and host-based targets involved in SARS-CoV-2 treatment. We anticipate optimistically that this perspective will provide the reader and researcher’s better understanding regarding COVID-19 and pave the path in the direction of COVID-19 drug discovery and development paradigm.

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Letter to the EditorConduction disorder and QT prolongation secondary to long-term treatment with chloroquine

Abstract

Drug induced QT prolongation and torsades de pointes

Heart

Chloroquine cardiomyopathy with conduction disorders

Heart

Letter to the Editor
Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine