ABSTRACT
Cardiovascular toxicity, defined as adverse drug reactions that primarily affect the heart, blood vessels, and blood constituents, is the primary cause for drug attrition during nonclinical and clinical development and for withdrawal of drugs from the marketplace. Numerous drugs have been shown to have the ability to induce potentially lethal cardiac arrhythmias, specifically torsades de pointes, by affecting cardiac electrophysiology, which was for a long time the focus of preclinical cardiovascular toxicity testing. However, a substantial number of drugs can also affect cardiac function beyond an interaction with the hERG channel and resulting alteration to the QT interval. Within this broader sense of cardiovascular toxicity, this chapter discusses key drug actions known to be involved in adverse drug effects on the cardiovascular system. It focuses on functional and mechanistic aspects rather than structural and descriptive parameters.
