Cardio-toxicity and ionic channels activities: Implications for Treatment and Prevention of Heart Diseases

Introduction: Drug-induced cardiac abnormalities and toxicities such as long-QT syndrome and other dysrhythmias are among major concerns in pharmacotherapy. Some dysrhythmias which could be acute or chronic, including ventricular arrhythmias often are life-threatening. Accumulating evidence supports the concept that a growing number of drugs may cause acquired forms of long-QT syndrome. Since affecting ionic channels activities implicated with majority of drug-induced long-QT syndrome, many regulatory agencies around the world require a rigorous in vitro electrophysiological testing to exclude inhibitory effect on hERG channels and induction of late sodium currents before transition to clinical studies in the process of developing new medicines. It is also a well-established belief that physicians must be aware of the risks of cardiotoxic consequences versus the beneficial therapeutic outcomes, when making decisions related to drug prescriptions. Therefore, the main objective of this presentation is to critically and comprehensively analyze the recently reported mechanisms of drug-induced life-threatening arrhythmias, sudden cardiac death and heart failure with a substantial focus on ionic channels involvement. Novel personal observations on protecting cardiac function against free radical oxygen species and other late sodium currents inducing agents will be also discussed. It is expected to adopt safer strategies in pharmacotherapy by highlighting molecular and cellular mechanisms of drug-induced cardiotoxicity.

کلیدواژه ها:

Pharmacotherapy ، Cardiotoxicity ، Ionic channels activity ، late sodium current