Drug Induced Torsades de Pointes: A Short Review

 

 

 

Article By:

I. Antao Pereira

R. Navelkar

 

Abstract:

Drug induced alteration in heart rate and rhythm are often encountered in clinical practice. Torsades de pointes (TdP), a polymorphic ventricular tachycardia with a prolonged QT interval, though often of very little consequence and self-limiting, can at times can be life threatening. The authors wish to highlight the various responsible drugs causing TdP with their common indications and likely causative mechanism(s). This would serve as a good guide to clinicians.

 

Introduction:

“Torsades” refers to an ornamental motif imitating twisted hairs or threads as seen on classical architectural columns and “pointes” referred to peaks or points.[1] Drug induced alteration in heart rate and rhythm are often encountered in clinical practice, percentages of which vary but to a maximum of 10% with known causative drugs.[2] However, though it is often of very little consequence and usually self-limiting, it can at times be life threatening. A patient who has been administered the offending/causative drug may not always complain about the problem which may then be rarely detected on an electrocardiogram (ECG) by chance or following vague complaints of discomfort and uneasiness felt by the patient.

Such a type of alteration in cardiac rhythm may be sudden and life threatening, enough to make it essential for the individual to seek emergency medical aid and/or admission and treatment including cardiac life support. Considering the seriousness of the irregular cardiac rhythm, the authors wish to highlight the various responsible drugs causing TdP with their common indications and likely causative mechanism(s). This would serve as a good guide to clinicians.

 

Definitions:

Torsades de pointes (TdP): It is described as a polymorphic ventricular tachycardia with prolonged QT interval, the occurrence of which is ascribed to marked prolongation of cardiac repolarization.[3]

Prolonged QT Interval: A QT interval over the 99th percentile should be considered abnormally prolonged. For both males and females, a QT interval>500 ms (milliseconds) is considered highly abnormal.[2,4]

The incidence of TdP varies from rare to maximum incidence of 10%[2,5-8] for known offending drugs. The risk of TdP ranges from approximately 0.001% for cisapride to approximately 8% for the antiarrhythmic drug quinidine.[2] The risk factors are usually hypokalemia  and  bradycardia.[1]

Herein described are the drugs that can cause prolongation of QT interval and as such can further on progress to cause TdP and subsequently  ventricular  fibrillation  and death.

TC-July2018-012 - Table 1 Drugs known to cause Torsades de Pointes

TC-July2018-013 - Table 1 Drugs known to cause Torsades de Pointes TC-July2018-014 - Table 1 Drugs known to cause Torsades de Pointes

Treatment of Torsades de pointes (TdP) includes:

  • Establish the diagnosis and identify the causative agent
  • Withdrawal of the causative factors/drugs[23]
  • Correction of  hypokalemia[2]

Measures to increase the heart rate which can be achieved by either using isoprenaline or cardiac pacing and intravenous administration of magnesium of 1-2 grams even if the magnesium level is normal.[2,41] If the episodes of TdP persist, it may be necessary to repeat infusions of magnesium sulfate.[2]

 

Discussion and Conclusion:

It must be noted that in most cases drugs used individually are responsible for the occurrence of TdP. However, in other circumstances, polytherapy or polypharmacy may be responsible for the occurrence of TdP due to pharmacokinetic drug interactions or additive pharmacological effects on the heart which further delay cardiac repolarization.

Other factors that can precipitate TdP in susceptible individuals include age>65 years (the elderly are also more frequently exposed to polypharmacy),[42,43] preexisting cardiac disease especially bradycardia,[2,44] female gender,[2,23,44,45] electrolyte imbalances especially hypokalemia[12,29]  and hypomagnesemia,[2,41,44-46] renal or hepatic dysfunction,[2] treatment with more than one QT prolonging drug,[12] and genetic predisposition.[2]

The analysis of TdP cases associated with non-cardiac drugs found that majority of the patients had two or more risk factors like preexisting heart disease, female gender, electrolyte imbalance, drug interactions, LQTS or high drug doses etc. These risk factors can be easily identified from medical history, thus drugs with known potential to cause TdP should be avoided in such patients.[11,45-47]

It is expected and very much possible that more drugs may and will be added to this list of drugs causing TdP with their possible mechanism(s) causing this untoward action. This will help in further improving our understanding and help to diagnose such causative agents as well as occurrence of a rare but important clinical situation requiring prompt and emergency medical management.

TC-July2018-015 - Authors Pg20

 

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