Norfine Mechanism of Action

Adrenergic and Dopaminergic Agent.
Pharmacology: Pharmacodynamics: Norepinephrine has a very potent action on alpha receptors and a more moderate effect on beta-1 receptors. Norepinephrine causes generalized vasoconstriction, except for the coronary vessels, which it dilates indirectly by increasing oxygen consumption. This results in an increase in the force (and in the absence of vagal inhibition) in the rate of myocardial contraction. Peripheral resistance increases, and diastolic and systolic pressures are raised.
The vascular effects of norepinephrine in the doses usually used clinically result from the simultaneous stimulation of alpha and beta adrenergic receptors in the heart and vascular system. Except in the heart, its action is predominantly on the alpha receptors. This results in an increase in the force and (in the absence of vagal inhibition) in the rate of myocardial contraction. Peripheral resistance increases, and diastolic and systolic pressures are raised.
Pharmacokinetics: Two stereoisomers of Norepinephrine exist, the biologically active L-isomer is the one present in Norepinephrine 1 mg/mL concentrate for solution for infusion.
Absorption: Subcutaneous: Poor.
Oral: Norepinephrine is rapidly inactivated in the gastro-intestinal tract following oral administration.
After intravenous administration Norepinephrine has a plasmatic half-life of about 1 to 2 minutes.
Distribution: Norepinephrine is rapidly cleared from plasma by a combination of cellular reuptake and metabolism. It does not readily cross the blood-brain barrier.
Biotransformation: Methylation by catechol-o-methyltransferase.
Deamination by monoamine oxydase (MAO).
Ultimate metabolite from both is 4-hydroxy-3-methoxymandelic acid.
Intermediate metabolites include normetanephrine and 3,4-dihydroxymandelic acid.
Elimination: Norepinephrine is mainly eliminated as glucuronide or sulphate conjugates of the metabolites in the urine.
Up to 16% of an intravenous dose is excreted unchanged in the urine with methylated and deaminated metabolites in free and conjugated forms.
Paediatric Population: No data on experience of pharmacokinetic studies in paediatric age groups is available.