scholarly journals Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: A systematic review

Author(s):  
Veronique Michaud ◽  
Pamela Dow ◽  
Sweilem B. Al Rihani ◽  
Malavika Deodhar ◽  
Meghan Arwood ◽  
...  

ABSTRACTBackgroundThe World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored.MethodsA thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds.ResultsEstimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds.ConclusionThe risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs.

2021 ◽  
Vol 22 (15) ◽  
pp. 8090
Author(s):  
Daniela Baracaldo-Santamaría ◽  
Kevin Llinás-Caballero ◽  
Julián Miguel Corso-Ramirez ◽  
Carlos Martín Restrepo ◽  
Camilo Alberto Dominguez-Dominguez ◽  
...  

Long QT syndromes can be either acquired or congenital. Drugs are one of the many etiologies that may induce acquired long QT syndrome. In fact, many drugs frequently used in the clinical setting are a known risk factor for a prolonged QT interval, thus increasing the chances of developing torsade de pointes. The molecular mechanisms involved in the prolongation of the QT interval are common to most medications. However, there is considerable inter-individual variability in drug response, thus making the application of personalized medicine a relevant aspect in long QT syndrome, in order to evaluate the risk of every individual from a pharmacogenetic standpoint.


2020 ◽  
Vol 27 (3) ◽  
pp. 42-52
Author(s):  
G. A. Golovina ◽  
K. V. Zaphiraki ◽  
E. D. Kosmacheva

In this review drug-induced long QT interval syndrome is described. The authors discuss approaches for the prevention, diagnosis, and treatment of this potentially fatal complication.


2013 ◽  
Vol 6 (5) ◽  
pp. 1002-1009 ◽  
Author(s):  
Christiaan C. Veerman ◽  
Arie O. Verkerk ◽  
Marieke T. Blom ◽  
Christine A. Klemens ◽  
Pim N.J. Langendijk ◽  
...  

1970 ◽  
Vol 6 (2) ◽  
pp. 73-82
Author(s):  
Filipe Santos Falani ◽  
Vinícius Nasser de Carvalho ◽  
Túlio Torres Vargas

Objetivo: Revisar a literatura em relação à associação do prolongamento do intervalo QT no eletrocardiograma e o uso de citalopram e escitalopram, antidepressivos de segunda geração de largo consumo em escala mundial. Materiais e Métodos: Revisão da literatura em bases de dados Scielo e Medline. Desenvolvimento: citalopram e escitalopram são antidepressivos conhecidos como indutores de QT Longo dose-induzida, e os riscos-benefícios devem ser avaliados antes de seu uso. O citalopram é o inibidor seletivo da recaptação da serotonina mais prescrito no mundo, enquanto o escitalopram é amplamente usado nas doenças depressivas maiores. O escitalopram é também amplamente prescrito devido seus efeitos colaterais leves e transitórios. A Síndrome do QT Longo ocorre devido uma alteração no sistema elétrico cardíaco. Uma duração do intervalo QT maior que 450ms em homens e 460ms em mulheres deve ser considerada anômala, com etiologia específica. Entretanto, arritmias cardíacas ocorrem mais frequentemente quando o QT é maior que 500ms. O principal mecanismo do QT Longo induzido por drogas é a inibição do canal de potássio hERG, particularmente naqueles pacientes com a variante polimórfica. Conclusão: Apesar da pequena prevalência de prolongamento do intervalo QT induzido em usuários de antidepressivos de segunda geração, dado seu amplo uso pela população, é necessária uma maior preocupação em relação à monitorização eletrocardiográfica, principalmente quando estiverem presentes fatores de risco ou sinais de overdose.Palavras-chave: Associação, Síndrome do QT Longo, Citalopram.ABSTRACTObjective: To review the literature regarding the association of QT prolongation on electrocardiogram and the use of citalopram and escitalopram, the second generation of wide consumption worldwide antidepressants. Materials and Methods: Literature review in Scielo and Medline databases. Development: Citalopram and escitalopram are antidepressants known as Long QT-inducing dose-induced, and the benefit-risk should be evaluated before use. Citalopram is the selective inhibitor of serotonin reuptake most widely prescribed in the world as escitalopram is widely used in major depressive disorder. Escitalopram is also widely prescribed because of its mild and transient side effects. The Long QT syndrome occurs because of a change in the cardiac electrical system. A duration of the QT interval greater than 450ms in men and 460ms in women should be considered anomalous, with specific etiology. However, cardiac arrhythmias occur more frequently when QT is greater than 500ms. The primary mechanism of drug-induced long QT is the inhibition of the hERG potassium channel, particularly in those patients with the polymorphic variant. Conclusion: Despite the low prevalence of QT interval prolongation induced in second-generation antidepressant users, given its wide use by the population, a greater concern for electrocardiographic monitoring is required, especially when there are risk factors or signs of overdose.Keywords: Association, Long QT Syndrome, Citalopram.


Cardiology ◽  
2012 ◽  
Vol 122 (1) ◽  
pp. 3-11 ◽  
Author(s):  
John Chiladakis ◽  
Andreas Kalogeropoulos ◽  
Fani Zagkli ◽  
Nikolaos Koutsogiannis ◽  
Konstantinos Chouchoulis ◽  
...  

2000 ◽  
Vol 8 (1) ◽  
pp. 52-53 ◽  
Author(s):  
Guo Xing Weng ◽  
Hang Ding ◽  
Juan Qi ◽  
Chun Xuan Xu

A 22-year-old female suffering from idiopathic long-QT syndrome complicated by frequent syncope, torsade-de-pointes-type ventricular tachycardia, and asthma, was successfully treated by video-assisted extensive left second and third thoracic sympathetic ganglionectomy, instead of left stellate and first thoracic ganglio-nectomy, to avoid postoperative Horner's syndrome. The QT interval was significantly shortened from 0.6 to 0.43 seconds four days after the surgery. It remained at 0.43 seconds during a 3-month follow-up with no recurrence of tachycardia or syncope.


2014 ◽  
Vol 83 (3) ◽  
pp. 250-254
Author(s):  
Jerzy Sacha

Long QT syndrome (LQTS) is a heart disorder characterized by a prolongation of the QT interval on ECG and a predisposition to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest or sudden cardiac death. This condition may be inherited or induced by external factors such as drugs, electrolyte imbalances and some acquired cardiac diseases. The review addresses LQTS caused by acute cardiac illnesses which are associated with a large amount of stunned myocardium, i.e. the reperfused myocardial infarction and the group of stress-related cardiomyopathies. In these cases, specific ECG evolutionary changes may be observed, i.e. dynamic deep T-wave inversion and QT interval prolongation which predispose to fatal polymorphic ventricular tachyarrhythmia, i.e. torsade de pointes. However, lethal arrhythmias are relatively rare in these instances and probably concern patients with an underlying predisposition to LQTS. The pathological mechanisms of both repolarization abnormalities and ventricular arrhythmias as well as the practical approach how to interpret electrocardiographic changes and identify high risk patients are discussed in this review.


2019 ◽  
Vol 16 (4) ◽  
pp. 65-72
Author(s):  
Violeta Ion ◽  
Cristina Pascari ◽  
Florina Cristescu

AbstractWe present the evaluation of a 82 years old patient, diagnosed with long QT syndrome at 75 years (QTc =550 ms) and obstructive hypertrophic cardiomyopathy from 2011, complicated with ventricular fibrillation and torsade de pointes (QTc =840ms). In this situation, it was decided to follow via electrocardiography (ECG) her first and second degree relatives (daughter - 53 years old – QTc =505 ms, granddaughter - 23 years old – QTc =448ms), and to inform them about the importance of performing the cardiac echography to exclude a possible obstructive hypertrophic cardiomyopathy, and of the genetic testing. After the implantation of the ICD (implantable cardiac defibrillator) and on treatment with beta-blockers, the patient did not repeat any arrhythmic events, but still had the same electrocardiographic aspect of long QT interval. Due to the fact that the patient had a lot of other diseases, the administration of treatment which can prolong the QT interval was avoided. Long QT syndrome represents a congenital or acquired pathology, which sometimes can be induced by some drugs, and requires a correct diagnosis in order to establish an individualized pharmaceutical or surgical treatment, and to prevent the risk of sudden death by cardiac arrhythmias.


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