Usage
Norepinephrine is primarily used to treat hypotension (low blood pressure) and shock. It’s prescribed for various conditions, including septic shock, cardiogenic shock, and other distributive shock. Its pharmacological classifications include vasopressor, inotrope, and adrenergic agonist. Norepinephrine works by mimicking the actions of the sympathetic nervous system, leading to vasoconstriction (narrowing of blood vessels) and increased heart contractility.
Alternate Names
Norepinephrine is also known as noradrenaline and levarterenol. Brand names include Levophed.
How It Works
Pharmacodynamics: Norepinephrine primarily acts on alpha-adrenergic receptors, causing vasoconstriction, which increases blood pressure. It also has some beta-1 adrenergic activity, resulting in increased heart rate and contractility.
Pharmacokinetics: Administered intravenously, norepinephrine is rapidly distributed and has a short half-life of about 2.4 minutes. It’s metabolized in the liver and other tissues by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Elimination is primarily renal.
Mode of Action: Norepinephrine binds to alpha-1 and beta-1 adrenergic receptors on the surface of cells. Binding to alpha-1 receptors on vascular smooth muscle leads to vasoconstriction, increasing systemic vascular resistance and blood pressure. Binding to beta-1 receptors in the heart increases heart rate and the force of contractions.
Elimination Pathways: Norepinephrine is metabolized by COMT and MAO, and the metabolites are primarily excreted in the urine.
Dosage
Standard Dosage
Adults:
Initial: 8-12 mcg/min IV infusion; titrate to effect.
Maintenance: 2-4 mcg/min IV infusion.
Children:
Initial: 0.05-0.1 mcg/kg/min IV infusion; titrate to effect.
Maximum: 1-2 mcg/kg/min.
Special Cases:
- Elderly Patients: Start at the lower end of the dose range due to potential for decreased organ function. Avoid administering into leg veins.
- Patients with Renal Impairment: Dose adjustments may be necessary based on individual patient response. Monitor closely.
- Patients with Hepatic Dysfunction: Dose adjustments may be necessary based on individual patient response. Monitor closely.
- Patients with Comorbid Conditions: Consider potential interactions and adjust as needed.
Clinical Use Cases
Dosages are titrated to effect in all cases, based on the patient’s hemodynamic response.
- Intubation: Use as needed to maintain blood pressure during the procedure.
- Surgical Procedures: Use as needed to support blood pressure.
- Mechanical Ventilation: Use as needed to manage hypotension.
- Intensive Care Unit (ICU) Use: Commonly used for managing hypotension and shock.
- Emergency Situations: Use as needed to treat life-threatening hypotension.
Dosage Adjustments
Adjustments are based on patient response and may be necessary in patients with renal or hepatic impairment, or other comorbid conditions.
Side Effects
Common Side Effects:
- Bradycardia (slow heart rate)
- Hypertension (high blood pressure)
- Arrhythmias (irregular heartbeat)
- Anxiety
- Headache
- Nausea and vomiting
- Tissue necrosis at injection site (due to extravasation)
Rare but Serious Side Effects:
- Severe hypertension
- Myocardial ischemia
- Stroke
- Acute kidney injury
- Limb ischemia
Long-Term Effects:
Data on chronic complications from prolonged use is limited, but potential risks include cardiac complications and vascular damage.
Adverse Drug Reactions (ADR):
Severe hypertension, arrhythmias, and tissue necrosis require immediate intervention.
Contraindications
- Hypersensitivity to norepinephrine
- Hypotension due solely to hypovolemia (fluid depletion)
- Peripheral vascular thrombosis (except in life-saving procedures)
- Concomitant use with certain general anesthetics (e.g., halothane, cyclopropane)
Drug Interactions
- MAOIs: Severe, prolonged hypertension.
- Tricyclic Antidepressants: Severe, prolonged hypertension.
- Alpha and Beta Blockers: Can lead to severe hypertension or diminished response to norepinephrine.
- General Anesthetics (e.g., halothane): Increased risk of arrhythmias.
Pregnancy and Breastfeeding
- Pregnancy: Use with caution if the benefits outweigh the risks. Norepinephrine can cross the placenta and potentially affect fetal circulation.
- Breastfeeding: No definitive information is available on the safety of norepinephrine during breastfeeding. Caution is advised.
Drug Profile Summary
- Mechanism of Action: Alpha- and beta-adrenergic agonist.
- Side Effects: Bradycardia, hypertension, arrhythmias, anxiety, headache, nausea/vomiting.
- Contraindications: Hypersensitivity, hypovolemia without fluid resuscitation, peripheral vascular thrombosis.
- Drug Interactions: MAOIs, tricyclic antidepressants, alpha/beta blockers.
- Pregnancy & Breastfeeding: Use with caution during pregnancy; limited information on breastfeeding safety.
- Dosage: Titrated to effect; typical adult maintenance 2-4 mcg/min IV.
- Monitoring Parameters: Blood pressure, heart rate, cardiac rhythm, urine output, peripheral perfusion.
Popular Combinations
Norepinephrine is often used in combination with other vasopressors and inotropes (e.g., dobutamine) in the management of shock.
Precautions
- Administer through a central venous catheter when possible to minimize risk of extravasation.
- Monitor blood pressure closely and titrate dose carefully.
- Treat hypovolemia (low blood volume) with fluids before starting norepinephrine.
- Extravasation can lead to tissue necrosis. Infiltrate the area with phentolamine if extravasation occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Norepinephrine?
A: Adult: Initial 8-12 mcg/min IV infusion, titrate to effect; maintenance 2-4 mcg/min IV. Pediatric: Initial 0.05-0.1 mcg/kg/min IV infusion, titrate to effect; maximum 1-2 mcg/kg/min.
Q2: How should Norepinephrine be administered?
A: Administer as a continuous IV infusion using an infusion pump, preferably through a central venous catheter.
Q3: What are the major side effects of Norepinephrine?
A: Bradycardia, hypertension, arrhythmias, anxiety, headache, extravasation leading to tissue necrosis.
Q4: What are the contraindications to using Norepinephrine?
A: Hypersensitivity, hypotension due solely to hypovolemia, peripheral vascular thrombosis (except in life-saving scenarios), concomitant use with certain general anesthetics.
Q5: What drugs interact with Norepinephrine?
A: MAOIs, tricyclic antidepressants, alpha and beta-blockers, some general anesthetics.
Q6: Can Norepinephrine be used during pregnancy?
A: Use with caution if the benefits outweigh the risks. It can cross the placenta and may affect fetal circulation.
Q7: Can Norepinephrine be used during breastfeeding?
A: Limited information is available about the safety of norepinephrine during breastfeeding. Exercise caution.
A: Stop the infusion immediately and aspirate any remaining drug. Infiltrate the area with phentolamine. Consider surgical consultation.
A: Metabolized by COMT and MAO. Primarily eliminated renally.
Q10: What is the difference between norepinephrine and epinephrine?
A: While both are adrenergic agonists, norepinephrine has predominantly alpha-adrenergic activity while epinephrine has more balanced alpha- and beta-adrenergic effects.
