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[New inotropic agents in the treatment of congestive heart failure]

M Freitas
Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology 1993, 12 Suppl 4: 19-28, 7-8
7904458
Significant advances are emerging in what concerns the newer inotropic agents. Despite the ideal agent, whose sole action is to increase the sensitivity of contractile proteins to calcium is yet to be found, the identification of specific receptors of dopamine in the CNS and peripheral circulation, had stimulated the pharmacological research of dopaminergic receptors agonists, selective for the subtypes DA1 and DA2, selective DA1 and DA2 antagonists and the dopamine beta-hidroxilase inhibitors and represent an unequivocal value. Beta-adrenergic agonists have been extensively evaluated as positive inotropic agents in the patients with congestive heart failure. Although norepinephrine, epinephrine and isoproterenol are potent stimulators of myocardial beta-adrenergic receptors, the clinical use of these agents has been limited by their positive chronotropic actions and their tendency to exacerbate cardiac arrhythmias (epinephrine and isoproterenol); their potent effects on vascular alpha 1-adrenergic receptors, which cause vasoconstriction (norepinephrine); and their effects on vascular beta 2 receptors, which cause vasodilation (isoproterenol). Dopamine, endogenous precursor of norepinephrine, is a sympathomimetic amine that has been widely used clinically as a cardiac stimulant. The effects of this drug are due to a combination of its actions on alpha, beta, and dopaminergic receptors, as well as a tyramine-like effect that causes the release of endogenous norepinephrine. Dopamine's positive inotropic effects are due principally to stimulation of cardiac beta-adrenergic receptors. At low doses it also stimulates renal dopaminergic receptors, thereby increasing renal cortical blood flow and promotion diuresis; higher doses causes stimulation of alpha 1-adrenergic receptors, resulting in increasing systemic arterial and venous pressures and, potentially, decrease renal blood flow. This vasoconstrictor action is frequently undesirable in patients with severe heart failure, and limits the drug's usefulness as a positive inotropic agent. Despite this risk, the use of synthetically derived catecholamines, i.e. dobutamine, has gained wide acceptance for the treatment of low output state associated with systemic hypotension. Despite the well reported down regulation of beta 1-adrenergic receptors in patients with chronic congestive heart failure, dobutamine consistently exerts hemodynamic benefits in this clinical situation. An attenuation of these benefits may be observed at times, although new tachyphylaxis very rarely occurs. Since dobutamine does not preferentially dilate the renal vasculature, concomitant administration of dopamine, at a dose which only stimulates the dopaminergic receptors in the renal artery, had the advantage of increasing renal perfusion and improving renal function. Administration of dopamine is often prolonged after that of dobutamine, and may help the wearing off of dobutamine.(ABSTRACT TRUNCATED AT 400 WORDS)

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