scholarly journals Safety and effectiveness of drug therapy for the acutely agitated patient (Part I)

2013 ◽  
pp. 127-136
Author(s):  
Gianluca Airoldi
Keyword(s):  
Heart Rate ◽  
Qt Interval ◽  
Physical Restraint ◽  
Safety Data ◽  
Surrogate Marker ◽  
Diagnostic Procedures ◽  
Torsades De Pointes ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Interval Prolongation

Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series) is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone). Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc) is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5) and Fridericia (QTc=QT/RR^0.33), both of which standardize themeasuredQTinterval to an RRinterval of 1 s (heart rate of 60 bpm).However, QT variability can also be influenced by other factors that are more difficult to measure, including body fat, meals, psycho-physical distress, and circadian and seasonal fluctuations.

scholarly journals QT Interval Prolongation as a Biomarker for Torsades de Pointes and Sudden Death in Drug Development

2002 ◽  
Vol 18 (2) ◽  
pp. 57-62 ◽  
Author(s):  
Gregory D. Sides
Keyword(s):  
Sudden Death ◽  
Qt Interval ◽  
Drug Effect ◽  
Torsades De Pointes ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Apparent Increase ◽  
Intrinsic Factors ◽  
Qt Interval Prolongation ◽  
Extrinsic And Intrinsic Factors

Prolongation of the QT interval on the surface 12-lead electrocardiogram is widely accepted as a biomarker for the potential of a drug to produce torsades de pointes and/or sudden death. Detection of drug-induced prolongation of the QT interval in animals and man is frequently confounded by extrinsic and intrinsic factors that limit the ability to detect a true drug effect. In particular drugs that increase heart rate show an apparent increase in QT interval that confounds assessment of a true drug effect on cardiac ventricular repolarization. The basis for the use of the QT interval as a biomarker will be examined.

A Síndrome do QT Longo Associada ao uso de Citalopram e Escitalopram / The Long QT Syndrome Associated to Citalopram and Escitalopram

1970 ◽  
Vol 6 (2) ◽  
pp. 73-82
Author(s):  
Filipe Santos Falani ◽  
Vinícius Nasser de Carvalho ◽  
Túlio Torres Vargas
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Second Generation ◽  
Long Qt ◽  
Drug Induced ◽  
Electrocardiographic Monitoring ◽  
System A ◽  
Qt Interval Prolongation ◽  
Qt Syndrome ◽  
Low Prevalence

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.

scholarly journals Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19

2021 ◽  
pp. 266-279
Author(s):  
Jarir At Thobari
Keyword(s):  
Qt Interval ◽  
Observational Studies ◽  
Torsade De Pointes ◽  
Conduction Block ◽  
Torsades De Pointes ◽  
Polymorphic Ventricular Tachycardia ◽  
Cardiac Events ◽  
Drug Induced ◽  
Qt Interval Prolongation ◽  
Reduction Of Mortality

Chloroquine (CQ) and Hydroxychloroquine (HCQ) are highly prescribed as medications for COVID-19 infection, although no robust or convincing data has yet been published about the efficacy in COVID-19 patients. Therefore, risk and benefit assessment are necessary for decision to prescribe these drugs in COVID-19 patient in hospitals settings. We systematically searched from MEDLINE Database which investigate the benefits and risks of HCQ and CQ among COVID-19 patients. All records were searched using the search terms Hydroxychloroquine, Chloroquine, COVID-19, and SARS-CoV-2. The selection criteria include all clinical trials and observational studies. We found 11 records about benefit and 7 records about risks on HCQ and CQ in COVID-19 patients after following inclusion and exclusion criteria. From clinical trial and observational studies have showed that HCQ is very limited benefit particularly on reduction of mortality or clinical improvement. Similarly, there were seven observational studies have estimated the cardiac event in use of HCQ or CQ in COVID-19. Even though no increase death, but these studies reported the increase risk of prolong QT-interval in high proportion and other cardiac events such as arrythmia, torsade de pointes and conduction block. We conclude that the benefit effect of HCQ and CQ in COVID-19 remains very limited. However, both medications have independently shown to increase the risk in other populations for QT-interval prolongation, drug-induced torsades de pointes/TDP (a form of polymorphic ventricular tachycardia) and drug-induced other cardiac events. 

scholarly journals Drug-Induced QT Prolongation as a Result of an Escitalopram Overdose in a Patient with Previously Undiagnosed Congenital Long QT Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Paul Singh ◽  
J. Martin Maldonado-Duran
Keyword(s):  
Qt Interval ◽  
Torsades De Pointes ◽  
Qt Prolongation ◽  
Long Qt ◽  
Drug Induced ◽  
Prolonged Qt Interval ◽  
Prolonged Qt ◽  
Qt Syndrome ◽  
Congenital Lqts ◽  
Congenital Long Qt Syndrome

We present a case of drug-induced QT prolongation caused by an escitalopram overdose in a patient with previously undiagnosed congenital LQTS. A 15-year-old Caucasian female presented following a suicide attempt via an escitalopram overdose. The patient was found to have a prolonged QT interval with episodes of torsades de pointes. The patient was admitted to the telemetry unit and treated. Despite the resolution of the torsades de pointes, she continued to demonstrate a persistently prolonged QT interval. She was seen by the cardiology service and diagnosed with congenital long QT syndrome. This case illustrates the potential for an escitalopram overdose to cause an acute QT prolongation in a patient with congenital LQTS and suggests the importance of a screening electrocardiogram prior to the initiation of SSRIs, especially in patients at high risk for QT prolongation.

scholarly journals Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation

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 ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Molecular Mechanisms ◽  
Torsade De Pointes ◽  
Individual Variability ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Interval Prolongation ◽  
Qt Syndrome ◽  
The Many

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.

scholarly journals Towards a better understanding of QT interval variability

2011 ◽  
Vol 2 (6) ◽  
pp. 245-251 ◽  
Author(s):  
Larisa G. Tereshchenko ◽  
Ronald D. Berger
Keyword(s):  
Qt Interval ◽  
Surrogate Marker ◽  
Polymorphic Ventricular Tachycardia ◽  
Drug Induced ◽  
Technical Requirements ◽  
Qt Interval Prolongation ◽  
Torsades Des Pointes ◽  
Qt Variability ◽  
Life Threatening ◽  
Qt Interval Variability

The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Guideline E14 recommends ‘Thorough QT Study’ as a standard assessment of drug-induced QT interval prolongation. At the same time, the value of drug-induced QTc prolongation as a surrogate marker for risk of life-threatening polymorphic ventricular tachycardia known as torsades des pointes remains controversial. Beat-to-beat variability of QT interval was recently proposed as an alternative metric. The following review addresses mechanisms of beat-to-beat QT variability, methods of QT interval variability measurements, and its prognostic value in clinical studies.

scholarly journals Can laypeople identify a drug-induced QT interval prolongation? A psychophysical and eye-tracking experiment examining the ability of nonexperts to interpret an ECG

2019 ◽  
Vol 26 (5) ◽  
pp. 404-411 ◽  
Author(s):  
Alaa Alahmadi ◽  
Alan Davies ◽  
Markel Vigo ◽  
Caroline Jay
Keyword(s):  
Heart Rate ◽  
Eye Tracking ◽  
Qt Interval ◽  
Just Noticeable Difference ◽  
Interval Length ◽  
Difference Threshold ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Qt Interval Prolongation ◽  
Single Complex

Abstract Objective The study sought to quantify a layperson’s ability to detect drug-induced QT interval prolongation on an electrocardiogram (ECG) and determine whether the presentation of the trace affects such detection. Materials and Methods Thirty layperson participants took part in a psychophysical and eye-tracking experiment. Following training, participants completed 21 experimental trials, in which each trial consisted of 2 ECGs (a baseline and a comparison stimulus, both with a heart rate of 60 beats/min). The experiment used a 1 alternative forced-choice paradigm, in which participants indicated whether or not they perceived a difference in the QT interval length between the 2 ECGs. The ECG trace was presented in 3 ways: a single complex with the signals aligned by the R wave, a single complex without alignment, and a 10-second rhythm strip. Performance was analyzed using the psychometric function to estimate the just noticeable difference threshold, along with eye-tracking metrics. Results The just noticeable difference 50% and 75% thresholds were 30 and 88 ms, respectively, showing that the majority of laypeople were able to detect a clinically significant QT-prolongation at a low normal heart rate. Eye movement data indicated that people were more likely to appraise the rhythm strip stimulus systematically and accurately. Conclusions People can quickly be trained to self-monitor, which may help with more rapid identification of drug-induced long QT syndrome and prevent the development of life-threatening complications. The rhythm strip is a better form of presentation than a single complex, as it is less likely to be misinterpreted due to artifacts in the signal.

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