Mechanisms of action of organic nitrates: a clinician´s perspective

T. Gori. University Medical Center Mainz, 2. Medizinische Klinik, 55131, Germany

Organic nitrates remain commonly employed drugs in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. The major issue with this type of therapies is the development of tolerance, ie the reduced hemodynamic effectiveness that is invariably seen upon prolonged administration. Traditionally, tolerance was seen simply as the loss of a beneficial phenomenon, rather than a true “side effect” of nitrates. More recent insights into the pharmacology of these drugs have revealed that the matter is more complex than previously thought. Organic nitrates have potent non-hemodynamic effects whose clinical relevance remains incompletely understood: these include the induction of oxidative stress, autonomic dysfunction, endothelial dysfunction, and the induction of ischemic preconditioning.

The pharmacology of organic nitrates has also been profoundly revised in the last decade: the role of mitochondria in the metabolism of some of these drugs (but not others) explains previously unappreciated, clinically relevant, differences in their use, and has potential clinical implications. These topics will be discussed from a clinician´s perspective.