Drug-Induced QT Prolongation and Torsades de Pointes: An All-Exclusive Relationship or Time for an Amicable Separation?

QT prolongation was perceived as a major antiarrhythmic mechanism, but soon became a surrogate for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity to no proarrhythmic action and even antiarrhythmic effects. Blockade of hERG channels is the primary cause of TdP, but blockade/activation of other channels can also be torsadogenic.

Should Domperidone be Used as a Galactagogue? Possible Safety Implications for Mother and Child.

Domperidone has been used as a galactagogue; however, solid evidence from an adequate sized randomized clinical trial is missing. Optimal dosage, start of treatment, length of treatment and scope of patients who can benefit also remain unknown. Although milk obtained after domperidone administration has not been shown to have untoward effects on newborns, no sufficiently large randomized clinical trial has been done to establish safety.

Disturbances of cardiac wavelength and repolarization precede Torsade de Pointes and ventricular fibrillation in Langendorff perfused rabbit hearts.

Drug-induced proarrhythmia is strongly focused on Torsade de Pointes (TdP), and QT prolongation is commonly used as a surrogate for TdP. This surrogate may be of limited value, as it produces false positives and false negatives. Cardiac electrophysiological parameters were obtained from monophasic action potentials recorded from Langendorff perfused female rabbit hearts.

Domperidone: limited benefits with significant risk for sudden cardiac death.

Background: Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism.

Methods And Results: Experiments were executed in isolated female rabbit hearts perfused for 150 minutes with domperidone 30, 60, or 100 nM.

Preclinical cardiovascular safety evaluations of biologics: optimizing the approach and follow-up.

Standard therapeutic agents (STA) are usually relatively small and simple molecules, which are synthesized as highly pure and consistent molecules. However, their target specificity can be low so that there is a liability for side effects at non-targeted receptors, enzymes or ion channels. Alternatively, highly specific and targeted small molecules can elicit cardiovascular liabilities due to their target-based effects.