[New inotropic agents in the treatment of congestive heart failure]. 1993

M Freitas
Faculdade de Medicina, Coimbra.

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)

UI MeSH Term Description Entries
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010726 Phosphodiesterase Inhibitors Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D011941 Receptors, Adrenergic Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013566 Sympathomimetics Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters. Amines, Sympathomimetic,Sympathomimetic,Sympathomimetic Agent,Sympathomimetic Drug,Sympathomimetic Agents,Sympathomimetic Drugs,Sympathomimetic Effect,Sympathomimetic Effects,Agent, Sympathomimetic,Agents, Sympathomimetic,Drug, Sympathomimetic,Drugs, Sympathomimetic,Effect, Sympathomimetic,Effects, Sympathomimetic,Sympathomimetic Amines
D015259 Dopamine Agents Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons. Dopamine Drugs,Dopamine Effect,Dopamine Effects,Dopaminergic Agents,Dopaminergic Drugs,Dopaminergic Effect,Dopaminergic Effects,Agents, Dopamine,Agents, Dopaminergic,Drugs, Dopamine,Drugs, Dopaminergic,Effect, Dopamine,Effect, Dopaminergic,Effects, Dopamine,Effects, Dopaminergic

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