Clinical pharmacology of inodilators

Recent advances in our knowledge of heart failure have shown that both a central and a peripheral factor are involved in this syndrome. Therefore, the ideal drug should combine the properties of a positive inotropic agent with those of a peripheral vasodilator; many drugs recently introduced into clinical practice have been shown to present both of these features, and the term "inodilators" has been used to characterize them. Inodilators can be further classified on the basis of their mechanism of action, i.e., phosphodiesterase inhibitors, and sympathomimetic and dopaminergic drugs. Phosphodiesterase inhibitors include bipyridine, imidazolone, and benzimidazole derivatives, which present potent inotropic and vasodilatatory actions. Despite their favorable acute effects, long-term studies have often yielded controversial, and sometimes disappointing, results as their chronic administration seems often to be associated with untoward effects and, above all, a poor prognosis. Sympathomimetic agonists act by stimulation of beta-receptors, with a consequent increase of myocardial contractility and peripheral vasodilation. Differently from the parenteral drugs (e.g., dobutamine), the oral agents present many important shortcomings including central nervous system effects, increased myocardial oxygen consumption, tachyarrhythmias, and, above all, development of tolerance during chronic administration. Dopaminergic drugs possess a unique pharmacologic profile since they add to the adrenergic stimulation their selective action on dopaminergic receptors. Dopamine is still one of the most useful drugs for the treatment of acute heart failure; the two oral drugs that more closely resemble its actions are levodopa and ibopamine. The administration of levodopa to patients with heart failure can induce a significant hemodynamic improvement that is maintained during chronic therapy. Ibopamine has been widely shown to cause a significant hemodynamic improvement in patients with heart failure. Its effects can be ascribed to a moderate increase of myocardial contractility accompanied by peripheral and renal vasodilatatory actions. This drug can also counteract some of the neurohumoral mechanisms (e.g., sympathetic stimulation and aldosterone secretion) that are activated in heart failure. These features can explain the favorable results that have also been recently obtained after the chronic administration of ibopamine.