Title: An Umbrella Review of Clinical Efficacy and Adverse Cardiac Events Associated with Hydroxychloroquine or Chloroquine with or Without Azithromycin in Patients with COVID-19

Context: The safety and efficacy of several repurposed drugs, including hydroxychloroquine and chloroquine, with or without azithromycin, were presumed to be miraculous in treating patients with COVID-19. However, as it later transpired, these therapeutic agents seem to be associated with critical adverse cardiac events. Objectives: Given the skepticism around the advantages and disadvantages of the aforementioned treatment strategies, the present study aimed to investigate the clinical efficacy and cardiac toxicity of hydroxychloroquine or chloroquine with or without azithromycin in the setting of COVID-19 infection. Method: This was an umbrella review conducted on patients with COVID-19 who received hydroxychloroquine or chloroquine with or without azithromycin from January 2020 to November 2020. We systematically searched PubMed, Scopus, Cochrane, ProQuest, Web of Science, and Embase databases. Results: Three studies (systematic review and meta-analysis) were analyzed to evaluate the arrhythmogenic potential of hydroxychloroquine or chloroquine with or without azithromycin in patients with COVID-19 and identify the clinical efficacy of such a combination. Conclusions: We found no benefit for patients with COVID-19 who received hydroxychloroquine or chloroquine alone or in combination with azithromycin. Moreover, it is noteworthy that these medications, particularly when considering co-administration, could result in both statistically and clinically elevated risks of notorious arrhythmias, such as TdP.

Potassium wasting nephropathy in the setting of tizanidine overdose: a case report

Background Hypokalemia has been rarely attributed to tizanidine, although the precise mechanism is unclear. Severe hypokalemia is a well-established cause of abnormalities involving cardiac conduction. Given this agent’s well-known cardiac arrhythmogenic potential, awareness of potential concomitant electrolyte abnormalities is important. Case presentation Electrolyte disorders, including hypokalemia, are rare complications of the antispasmodic medicine tizanidine when taken in doses as outlined by the manufacturer’s prescribing instructions. Although cases of severe hypokalemia have also been described in the literature in association with this agent, such reports are few. We report a Caucasian case of an intentional overdose involving a very large ingestion of tizanidine. In addition to the characteristic abnormalities on the electrocardiogram, our patient developed electrolyte derangements as well as self-limited acute kidney injury. These biochemical abnormalities included profound hypokalemia that was refractory to aggressive replacement over the ensuing several days, before eventually dissipating. A thorough assessment of the etiology of this hypokalemia was consistent with a defect in renal potassium handling. Conclusion In our patient with intentional tizanidine overdose, severe and refractory hypokalemia appears to have been due to a transient potassium wasting nephropathy.

QT Interval Monitoring and Drugs Management During COVID-19 Pandemic

While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti-virals (e.g. remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g. tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use however, are their possible effects on the QT interval and their arrhythmogenic potential. Some of this drugs have been in fact associated to QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. Aim of this review is to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physician dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.

Left Ventricular Regional Wall Motion Abnormality in the Setting of Acute Loperamide Overdose

Loperamide is an inexpensive, over-the-counter antidiarrheal agent with emerging reports of overdose due to its opioid properties. Although it is considered by many patients to be safe, cardiotoxicity has been reported, prompting the United States Food and Drug Administration to release a warning regarding the arrhythmogenic potential of loperamide. We present a case of a 32-year-old male presenting in acute loperamide overdose and subsequent cardiac dysrhythmia with focal wall motion abnormalities on echocardiogram. This finding has not been previously reported in the literature and is unique in this clinical presentation. We also highlight the potential mechanisms for loperamide cardiotoxicity and its challenging management.