PROARHYTHMIC EFFECTS OF DOXORUBICIN (LITERATURE REVIEW)

Abstract

For the treatment of oncological diseases, a fairly extensive Arsenal of effective chemotherapeutic drugs is used. One of the most widely used drugs is doxorubicinan anthracycline antibiotic with pronounced antitumor activity. The antitumor properties of doxorubicin are based on several main mechanisms: intercalation (insertion) into the DNA and inhibition of topoisomerase II, which leads to a violation of DNA synthesis and repair. Doxorubicin also contains a quinone fragment that participates in redox reactions with certain intracellular molecules, which leads to the formation of reactive oxygen species. The oxidative stress that occurs when doxorubicin is administered also causes the development of adverse cardiotoxic effects that disrupt the contractile function of the myocardium, which ultimately leads to chronic heart failure. To date, there are a significant number of review articles describing doxorubicin-induced heart failure, but there is not enough information about the relationship between doxorubicin and cardiac arrhythmias. This review discusses the proarrhythmic effects of doxorubicin and the pathophysiological mechanisms underlying them: the effect of doxorubicin on cardiac action potential, dynamics of intracellular calcium concentration, and cardiac ion currents.

Keywords

• doxorubicin
• anthracyclines
• cardiotoxicity
• cardiac arrhythmias
• pathophysiology
• reactive oxygen species