Pharmacology: Norepinephrine is a sympathomimetic amine which mainly acts through direct effect on α- and β-receptor on the heart. This causes peripheral vasoconstriction (α-adrenergic action), positive inotropic effect and coronary arterial dilatation (β-adrenergic action). These actions result in an increased systemic blood pressure and coronary arterial blood flow. In myocardial infarction accompanied with hypotension, norepinephrine usually increase aortic blood pressure, coronary arterial blood flow and myocardial oxygenation, thereby helping to limit the area of myocardial ischaemia and infarction. Venous return is increased and the heart tends to resume a more normal rate and rhythm than in the hypotensive state. If hypotension persists after correction of blood volume deficits, norepinephrine helps raise the blood pressure to an optimal level and establishes a more adequate circulation. However, norepinephrine effects in β1-receptor is lower than epinephrine or isoproterenol. It is believed that α-adrenergic effect resulted from inhibition of cyclic adenosine-31,51-monophosphate (AM)-production by inhibition of adenyl cyclase enzyme, whereas β-adrenergic is produced by stimulating the activity of adenyl cyclase.
Pharmacokinetics: Absorption: Oral ingestion of norepinephrine is destroyed in GI tract and it is poorly absorbed after SC injection. After IV administration, a pressor response occurs rapidly. Norepinephrine has a short duration of action and its pressure action stops within 1-2 min after infusion is discontinued.
Distribution: Norepinephrine localises mainly in sympathetic nervous system. It can pass through the placenta but not the blood-brain barrier.
Elimination: Pharmacological action of norepinephrine are terminated primarily by uptake & metabolism in sympathetic nerve endings. It is metabolised in the liver & other tissues by a combination of reactions involving catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). The major metabolites are normetanephrine and 3-methoxy-4-hydroxy mandelic acid (vanillylmandelic acid, VMA), both are inactive. Other inactive metabolites are 3-methoxy-4-dihydroxyphenylglycol, 3,4-dihydroxymandelic acid and 3,4-dihydroxyphenylglycol. Norepinephrine metabolites are excreted in urine, primarily as sulphate conjugates and to a lesser extent, as the glucuronide conjugates. Only a small quantity of norepinephrine are excreted in the unchanged form.