Norepinephrine is an extremely potent br and a1-adrenergic agonist. Its peripheral action is to induce intense vasoconstriction, particularly in the splanchnic and pulmonary vascular beds. The resultant increase in systemic vascular resistance opposes its inotropic effect. The clinical manifestation is an increase in blood pressure, with a mild increase in heart rate, but little or no change in cardiac output. To some degree, these effects are dose related, so that in the low-dose range norepinephrine has predominantly b-adrenergic action, whereas in the high-dose range its a-adrenergic vasoconstrictor effects are most prominent.

The dose for norepinephrine is usually in the range from 0.02 to 0.2 g/kg/min, with the very clear endpoint of achieving a mean arterial pressure of about 65 mmHg. Excessive doses of norepinephrine induce splanchnic and renal vasoconstriction, and tissue ischemia that may culminate in progressive metabolic acidosis and disseminated intravascular coagulation (DIC). Norepinephrine should be dosed to a specific clinical endpoint and weaned as soon as the clinical situation permits.

Renal autoregulation is lost in sepsis. Use of norepinephrine to restore normal perfusion pressure in septic patients with profound hypotension and oliguria has been shown to reverse acute renal dysfunction.

Alpha-receptor downregulation

As a potent direct-acting a1-adrenergic agonist, norepinephrine is indicated to maintain blood pressure in the presence of a rreceptor downregulation. This may occur after resection of a norepinephrine-secreting pheochromocytoma, long-term therapy (more than 3 weeks) with tricyclic antidepressants and monoamine oxidase inhibitors, and acutely during extracorporeal circulation which may in part explain low systemic vascular resistance states following cardiopulmonary bypass. In acute renal failure the renal arteries are much less sensitive to the vasoconstrictor effects of norepinephrine. This may be used to advantage in maintaining renal perfusion pressure during intermittent hemodialysis to avoid repeated hypotensive insults to the injured kidney.


Epinephrine is an endogenous catecholamine which is formed by the methylation of norepinephrine ('nor' is from the German N ohne Radikal, i.e. the nitrogen atom is without a methyl radical). Like norepinephrine, it acts on the cardiac b rreceptor and peripheral arreceptor to induce a combination of inotropy and vasoconstriction. Its ability to constrict venous beds augments venous return and cardiac preload. However, epinephrine also has substantial peripheral b .-receptor-mediated vasodilator activity. Thus, although the cutaneous, splanchnic, and pulmonary beds are constricted, skeletal muscle beds (which may receive up to 40 per cent of the cardiac output) are dilated. Therefore the effect of epinephrine on the systemic vascular resistance is more unpredictable than that of norepinephrine. When epinephrine is given in a low cardiac output state with high systemic vascular resistance, cardiac output increases and calculated systemic vascular resistance decreases. In contrast, when epinephrine is administered during anaphylaxis (high cardiac output, low systemic vascular resistance), it increases the systemic vascular resistance.

Like norepinephrine, the effect of epinephrine is predominantly b-adrenergic at lower doses but with increasing dosage vasoconstriction becomes more prominent. Epinephrine has potent chronotropic, dromotropic, and bathmotropic actions, increases myocardial work and oxygen consumption, and may exacerbate myocardial ischemia and induce dangerous tachyarrhythmias. Epinephrine is primarily indicated for low cardiac output states in the dosage range of 0.02 to 0.2 g/kg/min (20-200 ng/kg/min).

Epinephrine stimulates the Emden-Meyerhof pathway, and pyruvate production may actually increase lactic acid levels if the citrate acid cycle is impaired.


Dopamine is the naturally occurring precursor of norepinephrine. It is unique amongst endogenous catecholamines in that it has an agonist action on the dopaminergic (DA1 and Da2) receptors. DA1 receptors are situated in the blood vessels of the kidney and splanchnic bed, where they mediate vasodilation. There are also DA1 receptors in the lumen of the proximal renal tubule, where they promote sodium and water excretion. DA2 receptors are located in the presynaptic membrane When stimulated by free dopamine in the synaptic cleft, they suppress norepinephrine release from presynaptic storage vesicles. This promotes peripheral vasodilation, an action analogous to that of the presynaptic a .-adrenergic receptors. The dopaminergic effect of dopamine appears to be predominate in the low-dose range (0.5-3 g/kg/min).

At higher doses (3-10 g/kg/min), dopamine has modest b1-agonist activity, with minimal b2 peripheral vasodilator action, and maintains venous capacitance, preload, and blood pressure. Dopamine exerts about half its inotropic action indirectly through its conversion to or release of norepinephrine. At doses above 10 g/kg/min, dopamine induces progressive vasoconstriction via a 1-adrenergic mechanisms and norepinephrine release. In fact, there is a direct relationship between the dopamine dose and plasma norepinephrine levels. Excessive doses result in tachyarrhythmias, oliguria, and cutaneous vasoconstriction (skin necrosis and sloughing may occur when dopamine extravasates from a peripheral intravenous catheter).

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