Nor Adrenaline or Norepinephrine is a sympathomimetic amine derived from tyrosine. It is structurally identical to epinephrine but differs because it lacks a methyl group on its nitrogen atom. This difference makes it primarily agonistic at alpha1 and beta1 receptors, with little-to-no beta2 or alpha2 activity. At low doses (less than 2 mcg/min), the beta1 effects may be more pronounced and increase cardiac output. However, in doses higher than 3 mcg/min, the alpha1 effects may predominate. The increased activation of the alpha1 receptors will result in vasoconstriction and dose-dependent increases in systemic vascular resistance
after initiation of intravenous infusion, the steady-state plasma concentration is attained in 5 min. The half-life of norepinephrine is approximately 2.4 min. The apparent volume of distribution is 8.8 L. Plasma protein binding of norepinephrine is approximately 25%. Norepinephrine crosses the placenta, but it doesn't cross the blood-brain barrier(BBB). Norepinephrine is metabolized by the enzymes catechol-O-methyltransferase (COMT) and MAO in the liver and other tissues. The major metabolites are normetanephrine and vanillylmandelic acid, VMA); both are metabolically inactive. Only small quantities of norepinephrine are excreted unchanged. Noradrenaline metabolites are excreted in the urine primarily as sulfate conjugates and, to a lesser extent, as glucuronide conjugates.
It is available as an intravenous solution of 1 mg/mL, 4 mg/250 mL in dextrose 5%, and 8 mg/250 mL in dextrose 5%. Because of its relatively short half-life of 2.5 minutes, the administration of norepinephrine is typically by continuous infusion
A common technique is to start the infusion at 8 mcg to 12 mcg per minute and titrate to the desired pressure. The average maintenance dose is around 2 to 4 mcg per minute
It is worth noting that hypotension secondary to hypovolemia should have treatment with fluid resuscitation as a priority. Using vasopressors such as norepinephrine in a patient who has not had appropriate resuscitation may worsen ischemia and an overall decline in clinical status.
The most common adverse effects of norepinephrine relate directly to the activation of alpha1 receptors. In addition, excessive vasoconstriction can result in decreased end-organ perfusion, primarily caused by norepinephrine infusions without appropriately treating hypovolemia; this can be detrimental as most patients who require infusions of norepinephrine already have poor oxygen delivery or utilization
Care is necessary when using norepinephrine concomitantly with monoamine oxidase inhibitors or amitriptyline and imipramine-type antidepressants. Combining any of these drugs can lead to severe and prolonged hypertension.
Blood pressure requires close monitoring whenever vasopressors such as norepinephrine are used; this is possible via invasive or non-invasive measurement techniques. If following non-invasive measurements, it is recommended to obtain values every 2 to 3 minutes during initial titration and then at least every 5 minutes following the determination of the appropriate maintenance dose.
Extravasation into surrounding tissue can cause local ischemia and necrosis. In such cases, treatment is with a 10 to 15 mL saline solution containing 5 to 10 mg of phentolamine. Phentolamine is an alpha1 antagonist, and this method has shown the capability to significantly reduce adverse events of extravasation if given within 12 hours
