Drug induced QT prolongation and torsades de pointes

Yap, Yee Guan; Aj, Camm

doi:10.1136/heart.89.11.1363

Cited by 851 publications

(693 citation statements)

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“…This is particularly important since I Ks and I Kr are known to exhibit pharmacologically distinct properties. I Kr is not only a target of class III antiarrhythmic agents (14) but is also blocked by various, structurally unrelated drugs such as antipsychotics, H 1 -antihitamines, and fluoroquinolones (2). The most common mechanism of QT interval prolongation by pharmaceuticals appears to be inhibition of I Kr (2).…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Inhibition of the Slowly Activating Delayed Rectifier K+ Current in Guinea Pig Ventricular Cells

2004

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Abstract. Single ventricular cells were enzymatically isolated from guinea pig hearts and the effects of sevoflurane on the delayed rectifier K + current were investigated by the patch clamp method. The rapidly (I Kr ) and slowly activating delayed rectifier K + current (I Ks ) were isolated using chromanol 293B, a selective blocker for I Ks , a blocker for I Kr . Sevoflurane and halothane decreased I Ks in a concentration-dependent manner with an IC 50 value of 0.38 mM for sevoflurane and 1.05 mM for halothane. I Ks inhibition was characterized by suppression of maximum conductance with little effect on activation kinetics. Inhibition occurred immediately after anesthetic application and recovered upon wash-out. In contrast to the marked inhibition of I Ks , I Kr was hardly affected by sevoflurane. Under the current clamp, sevoflurane prolonged the action potential duration in a reversible manner and this effect was more marked when I Kr was inhibited by E4031. The results suggest that sevoflurane inhibits I Ks , and not I Kr , in a concentration-dependent manner at clinically relevant concentrations. The resulting prolongation of ventricular repolarization may partly account for the clinical observation of excessive QT prolongation by these anesthetics.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane Inhibition of the Slowly Activating Delayed Rectifier K+ Current in Guinea Pig Ventricular Cells

2004

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“…The cardiac cycle ends with closure of the Caþþ channels and activation of Kþ efflux channels, causing the potential to again approach ÿ90 mV (phase 3). It is this potassium efflux from the myocardial cell that is directly responsible for the QT interval on the ECG [3]. …”

Section: Cardiac Physiologymentioning

confidence: 99%

“…This triggered activity potentially can progress to re-entry and subsequent polymorphic ventricular tachycardia, or torsades de pointes [11]. These dysrhythmias are associated most commonly with QT intervals greater than 0.50 seconds, although the potential for dysrhythmia for a given QT interval varies from drug to drug and patient to patient [3]. In addition, there is not a simple relationship between the degree of drug-induced QT interval prolongation and the potential for the occurrence of torsades de pointes.…”

Section: Electrocardiographic Manifestationsmentioning

confidence: 99%

“…In addition, there is not a simple relationship between the degree of drug-induced QT interval prolongation and the potential for the occurrence of torsades de pointes. Drug-induced torsades de pointes can occur even without any substantial prolongation of the QT interval [3].…”

Section: Electrocardiographic Manifestationsmentioning

confidence: 99%

“…These medications all block the outward flow of potassium from intracellular to extracellular spaces. Myocardial repolarization is driven predominantly by this outward movement of potassium ions [3]. Blockade of the outward potassium currents by drugs may prolong the cardiac cycle action potential ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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ECG Manifestations: The Poisoned Patient

Holstege

Eldridge

Rowden

2006

Emergency Medicine Clinics of North America

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Emergency physicians routinely evaluate and manage poisoned patients. In 2003, more than 2 million human exposure cases were reported to poison centers throughout the United States [1]. Of those cases, 22% were treated in a health care facility with most of those cases evaluated in the emergency department. Cardiovascular drugs were listed as the fifteenth most frequently encountered human exposure (66,401) and the fifth leading cause of poisoning deaths.Drug-induced changes and abnormalities on the 12-lead electrocardiogram (ECG) are common. There are numerous drugs that can cause ECG changes and lead to cardiac dysrhythmias. The diagnoses and subsequent management of patients manifesting ECG changes following poisonings can challenge even the most experienced physician. Drugs that are advocated in Advanced Coronary Life Support protocols for cardiac dysrhythmias may not apply or may even worsen the condition of overdose patients [2].Despite that drugs have widely varying indications for therapeutic use, many unrelated drugs share a common cardiac pharmacologic effect if taken in overdose. The purpose of this article is to group together agents that cause similar electrocardiographic effects, review their pharmacologic actions, and discuss the electrocardiographic findings reported in the medical literature. The five main categories reviewed include potassium (Kþ) efflux blockers, sodium (Naþ) channel blockers, sodium-potassium adenosine-triphosphatase (Naþ/Kþ ATPase) blockers, calcium channel blockers (CCB), and beta-adrenergic blockers (BB). It is important to keep in mind, however, that many medications have actions that involve more than one of these

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Does This Patient With Palpitations Have a Cardiac Arrhythmia?

Thavendiranathan

Bagai

Khoo³

et al. 2009

JAMA

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Context Many patients have palpitations and seek advice from general practitioners. Differentiating benign causes from those resulting from clinically significant cardiac arrhythmia can be challenging and the clinical examination may aid in this process.Objective To systematically review the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations. MEDLINE (1950 to August 25, 2009 and EMBASE (1947 to August 2009) searches of English-language articles that compared clinical features and diagnostic tests in patients with palpitations with a reference standard for cardiac arrhythmia. Of the 277 studies identified by the search strategy, 7 studies were used for accuracy analysis and 16 studies for diagnostic yield analysis. Two authors independently reviewed articles for study data and quality and a third author resolved disagreements. Data Source, Study Selection, and Data ExtractionData Synthesis Most data were obtained from single studies with small sample sizes. A known history of cardiac disease (likelihood ratio [LR], 2.03; 95% confidence interval [CI], 1.33-3.11), having palpitations affected by sleeping (LR, 2.29; 95% CI, 1.33-3.94), or while the patient is at work (LR, 2.17; 95% CI, 1.19-3.96) slightly increase the likelihood of a cardiac arrhythmia. A known history of panic disorder (LR, 0.26; 95% CI, 0.07-1.01) or having palpitations lasting less than 5 minutes (LR, 0.38; 95% CI, 0.22-0.63) makes the diagnosis of cardiac arrhythmia slightly less likely. The presence of a regular rapid-pounding sensation in the neck (LR, 177; 95% CI, 25-1251) or visible neck pulsations (LR, 2.68; 95% CI, 1.25-5.78) in association with palpitations increases the likelihood of a specific type of arrhythmia (atrioventricular nodal reentry tachycardia). The absence of a regular rapid-pounding sensation in the neck makes detecting the same arrhythmia less likely (LR, 0.07; 95% CI, 0.03-0.19). No other features significantly alter the probability of clinically significant arrhythmia. Diagnostic tests for prolonged periods of electrocardiographic monitoring vary in their yield depending on the modality used, duration of monitoring, and occurrence of typical symptoms during monitoring. Loop monitors have the highest diagnostic yield (34%-84%) for identifying an arrhythmia.Conclusions While the presence of a regular rapid-pounding sensation in the neck or visible neck pulsations associated with palpitations makes the diagnosis of atrioventricular nodal reentry tachycardia likely, the reviewed studies suggest that the clinical examination is not sufficiently accurate to exclude clinically significant arrhythmias in most patients. Thus, prolonged electrocardiographic monitoring with demonstration of symptom-rhythm correlation is required to make the diagnosis of a cardiac arrhythmia for most patients with recurrent palpitations.

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Drug induced QT prolongation and torsades de pointes

Cited by 851 publications

References 18 publications

Sevoflurane Inhibition of the Slowly Activating Delayed Rectifier K+ Current in Guinea Pig Ventricular Cells

Sevoflurane Inhibition of the Slowly Activating Delayed Rectifier K+ Current in Guinea Pig Ventricular Cells

ECG Manifestations: The Poisoned Patient

Does This Patient With Palpitations Have a Cardiac Arrhythmia?

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