Predictable and less predictable unwanted cardiac drugs effects: individual pre-disposition and transient precipitating factors

In addition to their therapeutic effect, all drugs have unwanted effects. For the purpose of this MiniReview, unwanted drug effects will be discussed as either predictable, dose-dependent effects, or as less predictable events which only occur in patients pre-disposed to unwanted drug reactions when confronted with specific situations. While clinicians have long been using biomarkers to identify patients prone to less predictable unwanted drug effects, emerging data clearly suggest that such effects are often a consequence of interactions between drug effects, drug metabolism, an individual, at times genetically conferred pre-disposition to the interaction, and transient pre-disposing factors. This paper describes general principles of predictable and less predictable unwanted drug effects and discusses the complex interplay of genetic and acquired pre-disposing and precipitating factors for such effects using the example of ventricular pro-dysrhythmia. The latter, an important unwanted effect of many drugs, is a common yet not fully understood less predictable cardiac drug effect. Understanding the mechanisms of ventricular pro-dysrhythmia may allow to predict this unwanted drug effect better, and to identify novel markers for such events in the future.