Mitochondrial toxicity of cardiac drugs and its relevance to mitochondrial disorders.

INTRODUCTION

One target of toxicity caused by cardiac drugs is the mitochondrion. This review focuses on the mitochondrion-toxic effects of cardiac drugs and the extent to which mitochondrion-mediated side effects influence the treatment of cardiac disease in mitochondrial disorders (MIDs).

AREAS COVERED

Areas discussed in this review include the pathogenesis of mitochondrion toxicity and the mechanisms by which cardiac drugs exhibit their mitochondrion-toxic effect. Whenever available, the mitochondrion-toxic effect of cardiac drugs in patients with a MID is highlighted.

EXPERT OPINION

Most of the drugs used in cardiology are somewhat mitochondrion-toxic. The degree of toxicity, however, is variable and dependent on the type of drug, tissue, organ, subject, cell system investigated, the co-medication, and the conditions under which the investigations have been carried out. Abnormalities induced by mitochondrion-toxic cardiac drugs include impairment of respiratory chain functions resulting in reduced ATP production, increased production of reactive oxygen species with increased oxidation of proteins or lipids, reduction of the mitochondrial membrane potential and apoptosis. Several other mitochondrial functions may be additionally impaired by culprit compounds. Cardiac drugs that should be applied with particular caution in patients with MIDs include amiodarone, phenytoin, lidocaine, quinidine, isoproterenol, clopidogrel, acetyl-salicylic acid and molsidomine.