Norepinephrine information from DrugsUpdate
L - Caution when used during lactation
Noradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter.
As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled. Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle.
However, when norepinephrine acts as a drug it will increase blood pressure by its prominent increasing effects on the vascular tone from α-adrenergic receptor activation. The resulting increase in vascular resistance triggers a compensatory reflex that overcomes its direct stimulatory effects on the heart, called the baroreceptor reflex, which results in a drop in heart rate called reflex bradycardia.
Norepinephrine is synthesized from dopamine by dopamine β-hydroxylase. It is released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. The actions of norepinephrine are carried out via the binding to adrenergic receptors.
Norepinephrine is a direct-acting sympathomimetic which stimulates β1- and α-adrenergic receptors. Its α-agonist effects cause vasoconstriction, thereby raising systolic and diastolic BP with reflex slowing of heart rate.
Short; stops within 1-2 minutes after discontinuing the infusion.
Oral: Destroyed in the GI tract; SC: Poorly absorbed.
Mainly localises in sympathetic nervous tissue; crosses the placenta but not the blood-brain barrier.
Metabolised in the liver and in other tissues by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).
Via urine (mainly as metabolites).
Hypertension, headache, peripheral ischaemia, bradycardia, arrhythmias, anxiety, skin necrosis (with extravasation), dyspnoea, respiratory difficulty.
Because of the potency of Norepinephrine and because of varying response to pressor substances, the possibility always exists that dangerously high blood pressure may be produced with overdoses of this pressor agent. It is desirable, therefore, to record the blood pressure every two minutes from the time administration is started until the desired blood pressure is obtained, then every five minutes if administration is to be continued.
Symptoms: Hypertension, sweating, cerebral haemorrhage, convulsions.
Not a substitute for replacement of blood, plasma, fluids, and/or electrolytes; correct volume depletion prior to admin. Identify and correct hypoxia, hypercapnia and acidosis prior to or during admin. Avoid extravasation as tissue necrosis may occur. Avoid inj into leg veins, especially in elderly or those with occlusive vascular diseases, arteriosclerosis, DM or Buerger's disease. Hypertensive or hyperthyroid patients. In conjunction with local anaesthetics, do not use in fingers, toes, ears, nose or genitalia. Lactation.
Guanethidine, methyldopa, reserpine, TCAs may increase pressor response to norepinephrine.
Potentially Fatal: Increased risk of arrhythmias with cocaine, cyclopropane or halogenated hydrocarbon anaesthetics. Hypertensive crisis may occur with MAOIs. Hypertensive effects may be increased by nonselective β-blockers.
Acute hypotensive states
Adult: Initially, 8-12 mcg/minute, up to 8-30 mcg/minute in refractory shock. Infuse using a solution of 4 mcg/ml in glucose 5%, or sodium chloride 0.9% and glucose 5% at a rate of 2-3 ml/minute. Adjust according to BP response. Average maintenance dose: 0.5-1 ml/minute (2-4 mcg/minute). Infuse via a central venous catheter or into a large vein.
Child: Administer at a rate of 2 mcg/minute. Alternatively, 2 mcg/m2/minute. Adjust rate according to BP response and perfusion.
Elderly: Initial dose should be at low end of dose range.
Upper gastrointestinal haemorrhage
Adult: Intraperitoneal admin: 8 mg in 250 ml of 0.9% sodium chloride injection. Alternatively, instill 8 mg in 100 ml of 0.9% sodium chloride solution through a nasogastric tube every hr for 6–8 hours, then every 2 hours for 4–6 hours. Withdraw drug gradually.
Dilute with 5% glucose inj, with or without sodium chloride; dilution with sodium chloride inj alone is not recommended.
Incompatible with alkali and oxidising agents, barbiturates, chlorphenamine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium bicarbonate, sodium iodide, streptomycin, insulin.
List of Contraindications
Contraindicated in pregnancy
Caution when used during lactation
Safety and effectiveness in pediatric patients has not been established.
Clinical studies of Norepinephrine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Norepinephrine infusions should not be administered into the veins in the leg in elderly patients.
Hypertension. Pregnancy. Patients with peripheral or mesenteric vascular thrombosis unless necessary as a life-saving procedure.
Store at room temperature (25°C) and protect from light. Store in tight, light-resistant containers as norepinephrine is readily oxidised. Do not use if discoloured (e.g. pink, dark yellow, brown) or if there is a precipitate.