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Circulation Oct 2020Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and... (Review)
Review
Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient's arrythmia could be drug-induced is important.
Topics: American Heart Association; Arrhythmias, Cardiac; Electrocardiography; Risk Factors; United States
PubMed: 32929996
DOI: 10.1161/CIR.0000000000000905 -
British Journal of Clinical Pharmacology Mar 2016Torsades de pointes (TdP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface... (Review)
Review
Torsades de pointes (TdP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface electrocardiogram by QT interval prolongation. It typically occurs in self-limiting bursts, causing dizziness and syncope, but may occasionally progress to ventricular fibrillation and sudden death. Acquired long QT syndromes are mainly caused by cardiac disease, electrolyte abnormalities or exposure to drugs that block rectifying potassium channels, especially IKr. Management of TdP or marked QT prolongation includes removal or correction of precipitants, including discontinuation of culprit drugs and institution of cardiac monitoring. Electrolyte abnormalities and hypoxia should be corrected, with potassium concentrations maintained in the high normal range. Immediate treatment of TdP is by intravenous administration of magnesium sulphate, terminating prolonged episodes using electrical cardioversion. In refractory cases of recurrent TdP, the arrhythmia can be suppressed by increasing the underlying heart rate using isoproterenol (isoprenaline) or transvenous pacing. Other interventions are rarely needed, but there are case reports of successful use of lidocaine or phenytoin. Anti-arrhythmic drugs that prolong ventricular repolarization should be avoided. Some episodes of TdP could be avoided by careful prescribing of QT prolonging drugs, including an individualized assessment of risks and benefits before use, performing baseline and periodic electrocardiograms and measurement of electrolytes, especially during acute illnesses, using the lowest effective dose for the shortest possible time and avoiding potential drug interactions. These steps are particularly important in those with underlying repolarization abnormalities and those who have previously experienced drug-induced TdP.
Topics: Anti-Arrhythmia Agents; Disease Management; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 26183037
DOI: 10.1111/bcp.12726 -
Postgraduate Medical Journal Jul 2021Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac... (Review)
Review
Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a 'corrected QT' (QTc) value. Normal QTc intervals are typically <450 ms for men and <460 ms for women. For every 10 ms increase, there is a ~5% increase in the risk of arrhythmic events. When prescribing drugs associated with QT prolongation, three key factors should be considered: patient-related risk factors (eg, female sex, age >65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.
Topics: Humans; Long QT Syndrome; Patient Care Management; Practice Patterns, Physicians'; Risk Adjustment; Torsades de Pointes
PubMed: 33122341
DOI: 10.1136/postgradmedj-2020-138661 -
Frontiers in Physiology 2022
PubMed: 35800346
DOI: 10.3389/fphys.2022.947103 -
Cancers Mar 2020Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A...
Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported cases related to TKIs. Signal of Disproportionate Reporting (SDR) was found for cardiac failure, ischemic heart disease, cardiac arrhythmias, /QT prolongation, hypertension, and pulmonary hypertension. Dasatinib and bosutinib were related to the highest disproportionality for cardiac failure. Nilotinib was associated with the highest SDR for ischemic heart disease, /QT prolongation and cardiac arrhythmias. Only ponatinib was related to an SDR for hypertension, while dasatinib and imatinib were related to pulmonary hypertension. In the context of CML, TKIs have different safety profiles related to CV events, among which nilotinib seems particularly related to. These results claim for a revision of its CV safety profile mainly for the risk of /QT prolongation.
PubMed: 32235443
DOI: 10.3390/cancers12040826 -
Cureus Jan 2021Background Amiodarone causes less drug-induced torsade de pointes (TdP) compared to other class III antiarrhythmics. Two theories proposed for this finding include that...
Background Amiodarone causes less drug-induced torsade de pointes (TdP) compared to other class III antiarrhythmics. Two theories proposed for this finding include that amiodarone has less repolarization heterogeneity, and/or decreases early after depolarization (EADs). Corrected QT (QTc) dispersion as measured on a surface electrocardiogram (ECG) represents spatial heterogeneity of ventricular repolarization. Objective The purpose of this study was to analyze the difference in QT dispersion between amiodarone and other class III antiarrhythmics and to determine the etiology of TdP. Methods This was a retrospective, observational study at Montefiore Medical Center between January 2005 and January 2015. Inclusion criteria were adults >18 years on amiodarone, dofetilide, or sotalol with prolonged QT interval on 12-lead ECG. ECGs were reviewed by three blinded observers. QTc was calculated using the Bazett and Framingham formulas. QTc dispersion was calculated by subtracting the shortest from the longest QTc. Analysis of variance (ANOVA) was applied for comparison between antiarrhythmic groups with Bonferroni correction for multiple comparisons. Results A total of 447 ECGs were reviewed and 77 ECGs met inclusion criteria. The average QT dispersion for amiodarone, dofetilide, and sotalol was 0.050, 0.037, and 0.034, respectively (p=0.006) and the average QTc dispersion by Bazett was 0.053, 0.038, and 0.037 (p=0.008) and by Framingham was 0.049, 0.036, and 0.035 (p=0.009), respectively. Conclusion Our results show that given the increase in QT dispersion seen with amiodarone, heterogeneous ventricular repolarization as measured by QTc dispersion likely does not account for the lower incidence of drug-induced TdP seen with amiodarone. The ability of amiodarone to decrease EADs via sodium-channel blockade is more likely the explanation for its lower incidence of drug-induced TdP.
PubMed: 33643739
DOI: 10.7759/cureus.12895 -
Journal of the American Heart... Feb 2021
Topics: Arrhythmias, Cardiac; Gonadotropins; Humans; Testosterone; Torsades de Pointes
PubMed: 33599137
DOI: 10.1161/JAHA.120.020300 -
Postepy Dermatologii I Alergologii Jun 2014Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and... (Review)
Review
Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the 'rapid' I Kr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk.
PubMed: 25097491
DOI: 10.5114/pdia.2014.43191 -
Global Cardiology Science & Practice Jun 2017Literature about torsade de pointes induced by azole antifungal agents is scarce, despite the well-known association. Furthermore, little is known about the latency... (Review)
Review
Literature about torsade de pointes induced by azole antifungal agents is scarce, despite the well-known association. Furthermore, little is known about the latency time between commencing an azole antifungal agent and developing torsade de pointes. The objectives of the present study were therefore to identify all cases of torsade de pointes associated with systemic azole antifungal use reported to the WHO monitoring centre (Uppsala, Sweden) and to determine the latency times between commencing the azole and developing torsade de pointes. Investigator-driven, retrospective, descriptive analysis of post-marketing pharmacovigilance data regarding systemic azole antifungal agents and the development of torsade de pointes reported to the WHO monitoring centre 1995-2015. 191 cases were reported as follows: fluconazole 130, itraconazole 22, ketoconazole 5, posaconazole 1, voriconazole 33. More than half of all cases involved concomitant suspected or interacting drugs. The median latency times between starting the azole and developing torsade de pointes ranged from 1 (posaconazole) - 9.5 days (itraconazole), range <1-250). Clinicians should be aware of these features of azole-associated torsade de pointes, avoid interacting drugs if at all possible and monitor at-risk patients.
PubMed: 29644223
DOI: 10.21542/gcsp.2017.11