A Review of Erythromycin-Induced Malignant Tachyarrhythmia— Torsade de Pointes

Abstract

The term torsade de pointes refers to a ventricular tachycardia characterized by QRS complexes of changing amplitude that appears to twist around the isoelectric line and occurs at rates of 200-250/minute. Most cases of torsade de pointes are iatrogenically induced by drugs or electrolyte abnormalities. The most important feature is QT interval prolongation. Torsade de pointes was first described in 1966 in France by Dessertenne. The authors report a case of a fifty-year-old woman with medical history of corrective surgery for tetralogy of Fallot who was admitted to the hospital with pneumonia and atrial fibrillation and later developed recurrent episodes of polymorphic ventricular tachycardia with QT interval prolongation after i.v. administration of erythromycin. The episodes did not recur after discontinuation of erythromycin, and the QT interval returned to normal. The association of erythromycin with torsade de pointes has been reported in 18 cases to date. Erythromycin has been shown to produce electrophysiologic effects similar to those of class Ia and class III antiarrhythmic drugs on the cardiac muscle. This potentially fatal complication of a commonly used antibiotic is rare, but increased physician awareness is important, especially in patients with predisposing factors like electrolytes abnormalities, use of class Ia and Class III antiarrhythmic drugs, and presence of prolonged QT interval (congenital prolonged QT syndromes). This is the second case reported in a patient with previous cardiac surgery and erythromycin administration.

QTc prolongation with concurrent use of azithromycin and diltiazem in an old female patient: a case report

“…It also causes EAD and triggered activity in M cells, resulting in increased dispersions of refractoriness in ventricular tissue and torsade de pointes. 15,17 Since azithromycin and diltiazem both act on the I Kr , therefore they may have had additive effects on the potential action duration which resulted in QTc interval prolongation and Torsade de pointes in this patient.…”

“…[15][16][17][18] Many factors may contribute to higher drug serum concentrations such as higher than average drug dosage and decreased clearance. Decreased drug clearance is observed in patients with liver or kidney impairment and in patients taking agents that may interfere with their clearance.…”

Preclinical Electrophysiology Assays of Mitemcinal (Gm-611), a Novel Prokinetic Agent Derived From Erythromycin

“…Cisapride, a piperidinyl benzamide prokinetic agent used for the treatment of gastrointestinal disorders, was withdrawn from the market in the United States in 2000 because of its propensity to prolong the QT interval, leading to lifethreatening TdP arrhythmias (Wysowski and Bacsanyi, 1996). Several macrolides, such as erythromycin (Katapadi et al, 1997) and clarithromycin (Kamochi et al, 1999;Lee et al, 1998) have also been associated with QT risk interval prolongation and TdP. Although mitemcinal is also a macrolide in the same chemical class, the in vitro and in vivo QT prolonging effects have remained obscure.…”

The Dog's Role in the Preclinical Assessment of QT Interval Prolongation

“…A cursory examination of the compounds associated with these properties reveal a highly diverse chemical structure set and seemingly nonrelated pharmacological targets. These therapeutics include several antibiotics (24,35) (some macrolides; erythromycin and other protein synthesis inhibitors, fluoroquinolones, DNA synthesis inhibitors; grepafloxacin), antifungals (3, 57) (fluconazole, ketoconazole), an agent for gastrointestinal prokinesis (17,37,50,66) (cisapride), histamine H1 receptor antagonists (5,9,14,25,36,38,39,72,75) (terfenadine, diphenhydramine, astemizole, phenothiazine derivatives), as well as antipsychotic agents (44) (phenothiazine derivatives, haloperidol, sertindole, risperidone). These compounds, although certainly not meant to be an exhaustive list, have been shown to cause serious and potentially fatal cardiac arrhythmias.…”