Assessing predictors of drug-induced torsade de pointes.
Torsades de pointes (TdP) is a malignant polymorphic ventricular tachyarrhythmia that can be caused by drugs that induce electrophysiological changes. Although the number of drugs known to cause TdP has increased in recent years, there is no cell-based assay, in vitro heart preparation or animal model that predicts the potential of a drug to induce TdP in humans. Nevertheless, certain electrophysiological events are known to be associated with the development of TdP. For example, a drug that prolongs action potential duration, induces early afterdepolarizations and ectopic beats, and increases dispersion of ventricular repolarization is likely to cause TdP. By contrast, a drug that does not induce these changes is unlikely to cause TdP. The exact relationship between these electrophysiological events and the development of TdP has not been defined, but the potential of a drug to elicit these events might predict its pro-arrhythmic risk.
Belardinelli
Luiz
L
CV Therapeutics, 3172 Porter Drive, Palo Alto, CA 94304, USA. luiz.belardinelli@cvt.com
Antzelevitch
Charles
C
Vos
Marc A
MA
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D006634:Histamine H1 Antagonists / Q000009:adverse effects; D006801:Humans; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D006634:Histamine H1 Antagonists