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Swiss Medical Weekly May 2005Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. It prolongs the QT-interval and is mainly metabolized by the isoenzyme... (Review)
Review
Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. It prolongs the QT-interval and is mainly metabolized by the isoenzyme CYP3A4 of the hepatic cytochrome-P450-system, which is used by numerous other QT-prolonging agents. Its most severe side effect is the development of life-threatening Torsade de pointes ventricular tachycardia in the setting of a prolonged QT-interval. Since drug addicts are prone to concomitant medical conditions requiring additional medication as well as to continued abuse of cocaine, they are at higher risk for developing this major complication of methadone therapy. Before subjecting patients on methadone to other drugs, the QT-interval should be determined and it should be ascertained whether the new agent has the property to prolong the QT-interval or is metabolised by the cytochrome-P450 system.
Topics: Adult; Analgesics, Opioid; Cocaine-Related Disorders; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Methadone; Torsades de Pointes
PubMed: 15986265
DOI: 10.4414/smw.2005.10939 -
Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation.Europace : European Pacing,... Jun 2023Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the...
AIMS
Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP).
METHODS AND RESULTS
We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C.
CONCLUSION
These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.
Topics: Humans; Torsades de Pointes; Computer Simulation; Long QT Syndrome; Mutation; DNA-Binding Proteins; ERG1 Potassium Channel
PubMed: 37386841
DOI: 10.1093/europace/euad161 -
Annals of Palliative Medicine May 2020Prolongation of the QT interval by antiarrhythmic drugs is the primary cause of torsade de pointes. Although there are previous reports of drug-induced torsade de...
Prolongation of the QT interval by antiarrhythmic drugs is the primary cause of torsade de pointes. Although there are previous reports of drug-induced torsade de pointes in patients undergoing hemodialysis, torsade de pointes caused by a sudden decrease of potassium levels in patients initiating hemodialysis has not been well described. A 70-year-old woman with recurrent bilateral gluteal abscesses visited the hospital for antibiotic treatment. Twenty-eight days after admission, atrial fibrillation with rapid ventricular rhythm was newly detected and was controlled with intravenous amiodarone treatment. After developing pulmonary edema that did not improve with diuretic treatment, she underwent emergency hemodialysis. During hemodialysis, serum potassium and magnesium levels decreased to 3.1 and 1.7 mg/dL, respectively. The electrocardiogram showed torsade de pointes. Amiodarone treatment was stopped, and magnesium sulfate was infused. A higher concentration of potassium dialysate was used in continuous renal replacement therapy. Torsade de pointes episodes halted, and QT interval prolongation normalized. We describe a case with a rare complication of torsade de pointes upon initiating hemodialysis in a patient with QT prolongation. When initiating hemodialysis, serum potassium levels as well as electrocardiograms should be monitored in patients with a prolonged QT interval.
Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Female; Humans; Long QT Syndrome; Renal Dialysis; Torsades de Pointes
PubMed: 32389016
DOI: 10.21037/apm.2020.04.29 -
BMC Pharmacology & Toxicology Jan 2022Since an introduction of an ICH guidance in 2005, no new drugs were withdrawn from the market because of the causation of Torsade de Pointes (TdP). However, the risk of...
Since an introduction of an ICH guidance in 2005, no new drugs were withdrawn from the market because of the causation of Torsade de Pointes (TdP). However, the risk of TdP is still a concern for marketed drugs. TdP is a type of polymorphic ventricular tachycardia which may lead to sudden cardiac death. QT/QTc interval prolongation is considered a sensitive, but not specific biomarker. To improve the effectiveness of studies' workflow related to TdP risk prediction we created an extensive, structured, open-access database of drug-related TdP cases. PubMed, Google Scholar bibliographic databases, and the Internet, via the Google search engine, were searched to identify eligible reports. A total of 424 papers with a description of 634 case reports and observational studies were included. Each paper was manually examined and listed with up to 53 variables related to patient/population characteristics, general health parameters, used drugs, laboratory measurements, ECG results, clinical management, and its outcomes, as well as suspected drug's properties and its FDA adverse reaction reports. The presented database may be considered as an extension of the recently developed and published database of drug cardiac safety-related information, part of the tox-portal project providing resources for cardiac toxicity assessment.
Topics: Cardiotoxicity; Databases, Factual; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 35012678
DOI: 10.1186/s40360-021-00548-0 -
Clinical Cardiology Mar 1997The term torsade de pointes refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. While the most common cause is... (Review)
Review
The term torsade de pointes refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. While the most common cause is treatment with QT prolonging drugs, torsade de pointes also occurs in the congenital long QT syndromes and in the setting of acquired heart block or severe electrolyte disturbance, notably hypokalemia. Among QT prolonging drugs that cause torsade de pointes, both antiarrhythmics and "noncardioactive" drugs have been recognized. The electrocardiographic features of torsade de pointes include labile QT intervals, prominent U waves, and a "pause-dependent" onset of the arrhythmia. Treatment consists of recognition of the syndrome, correction of underlying electrolyte abnormalities, and withdrawal of any offending drugs. Magnesium, isoproterenol, or cardiac pacing provides specific antiarrhythmic therapy in torsade de pointes.
Topics: Electrocardiography; Humans; Long QT Syndrome; Risk Factors; Torsades de Pointes
PubMed: 9068917
DOI: 10.1002/clc.4960200318 -
The Netherlands Journal of Medicine Jun 2017We report a case of a 48-year-old female patient with newly diagnosed multiple myeloma. She developed recurrent torsade de pointes and required cardiopulmonary...
We report a case of a 48-year-old female patient with newly diagnosed multiple myeloma. She developed recurrent torsade de pointes and required cardiopulmonary resuscitation and defibrillation. Atrial arrhythmias in patients with multiple myeloma and hypercalcaemia have been described, but, to the best of our knowledge, this is the first report of torsade de pointes in this setting.
Topics: Fatal Outcome; Female; Humans; Hypercalcemia; Middle Aged; Multiple Myeloma; Torsades de Pointes
PubMed: 28653942
DOI: No ID Found -
Journal of General Internal Medicine Mar 2020One of the more challenging aspects of ECG interpretation is measurement and interpretation of the QT interval. This interval represents the time taken for the... (Review)
Review
One of the more challenging aspects of ECG interpretation is measurement and interpretation of the QT interval. This interval represents the time taken for the ventricles to completely repolarise after activation. Abnormal prolongation of the QT interval can lead to torsades de pointes, a form of potentially life-threatening polymorphic ventricular tachycardia (VT). Detection of a prolonged QT interval is essential as this can be a reversible problem, particularly in the context of the use of a variety of commonly prescribed medications in the hospital setting. Automated ECG printouts cannot be relied upon to diagnose QT interval prolongation; thus, the onus is on the clinician to identify it. This is a difficult task, as the normal QT interval is typically measured relative to the heart rate. Therefore, the QT interval often requires "correction" for the current heart rate, in order to correctly stratify the risk of torsades de pointes. A wealth of correctional formulae have been derived, but none has proven superior. We present an approach to the ECG in this context, and a step-by-step guide to manually measuring and correcting the QT interval, and an approach to management in common hospital-based clinical scenarios.
Topics: Electrocardiography; Humans; Long QT Syndrome; Physicians; Torsades de Pointes
PubMed: 31654357
DOI: 10.1007/s11606-019-05477-7 -
Medicine Jul 2003Numerous medications, including drugs prescribed for noncardiac indications, can lead to QT prolongation and trigger torsade de pointes. Although this complication... (Review)
Review
Numerous medications, including drugs prescribed for noncardiac indications, can lead to QT prolongation and trigger torsade de pointes. Although this complication occurs only rarely, it may have lethal consequences. It is therefore important to know if patients with torsade de pointes associated with noncardiac drugs have risk factors that are easy to identify. We reviewed reports of drug-induced torsade de pointes and analyzed each case of torsade de pointes associated with a noncardiac drug for the presence of risk factors for the long QT syndrome that can be easily identified from the medical history or clinical evaluation (female gender, heart disease, electrolyte disturbances, excessive dosing, drug interactions, and history of familial long QT syndrome). We identified 249 patients with torsade de pointes caused by noncardiac drugs. The most commonly identified risk factor was female gender (71%). Other risk factors were frequently present (18%-41%). Virtually all patients had at least 1 of these risk factors, and 71% of patients had 2 or more risk factors. Our study suggests that almost all patients with torsade de pointes secondary to noncardiac drugs have risk factors that can be easily identified from the medical history before the initiation of therapy with the culprit drug.
Topics: Anti-Bacterial Agents; Antipsychotic Agents; Female; Histamine H1 Antagonists; Humans; Male; Risk Factors; Sex Distribution; Torsades de Pointes
PubMed: 12861106
DOI: 10.1097/01.md.0000085057.63483.9b -
Europace : European Pacing,... Sep 2007
Topics: Atrial Fibrillation; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 17766319
DOI: 10.1093/europace/eum165 -
Progress in Biophysics and Molecular... May 2016
Editorial to "Disturbances of cardiac wavelength and repolarization precede torsade de pointes and ventricular fibrillation in langendorff perfused rabbit hearts" by Luc Hondeghem: It is difficult to make predictions, especially about the future∗: Thoughts about forecasting cardiotoxicity of...
Topics: Animals; Cardiotoxicity; Electrocardiography; Heart; Heart Conduction System; Rabbits; Torsades de Pointes; Ventricular Fibrillation
PubMed: 27137834
DOI: 10.1016/j.pbiomolbio.2016.04.001