SYMPATHOMIMETIC AMINES



Potent, parenteral inotropic agents other than digitalis are sometimes required in severe heart failure, the two most common being dopamine and dobutamine. These are sympathomimetic agents producing less tachycardia and fewer pe­ripheral vascular effects than the older drugs nor­epinephrine, epinephrine, and isoproterenol. Do­pamine stimulates the myocardium by activating betai-adrenergic receptors directly and indirectly by releasing norepinephrine from sympathetic nerve terminals. Dopamine at low doses (2 jxg/kg/ min) activates dopaminergic receptors in the renal, mesenteric, coronary, and cerebral vascular beds and causes vasodilation. This is partially re­sponsible for dopamine-induced diuresis in pa­tients with severe congestive heart failure (renal vasodilator plus inotropic effects). With larger doses of dopamine (5 to 10 ^.g/kg/mm), alpha-ad-renergic agonism similar to that of norepineph­rine causes peripheral vasoconstriction. Thus, with infusion of 2 to 5 |xg/kg/min, renal blood flow, cardiac contractility, and cardiac output all increase with little change in the heart rate and possibly a small decrease in peripheral vascular resistance. Higher doses (5 to 10 u.g/kg/min) begin to increase arterial pressure, peripheral vascular resistance, and heart rate. In patients with hy­potension, the vasconstrictor effects of doses up to 20 |j.g/kg/min may be desired. The elevation of heart rate, contractility, and blood pressure as­sociated with dopamine may increase oxygen demand, but if cardiac performance is improved and cardiac size decreases, the net oxygen consump­tion may not be adversely affected.
Dobutamine increases cardiac contractility but has less effect on the peripheral vasculature than dopamine. It is useful when the vasoconstrictive effects of higher dopamine doses are to be avoided. Dobutamine does not have the renal va-sodilatory effects of dopamine. It is administered intravenously in a dose of 5 to 10 u.g/kg/min.
Amrinone is a noncatecholamine, nondigitalis positive inotropic agent with vasodilator activity. It is available for short-term intravenous use in patients with severe congestive heart failure. Mil­rinone is an orally active inotropic agent under investigational use in the United States.







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