NOREPINEPHRINE

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Norepinephrine, also known as noradrenaline, is an important neurotransmitter and hormone in the human body. It plays a crucial role in various physiological processes, including the regulation of blood pressure, heart rate, and stress response. In the context of anesthesia, norepinephrine is significant for several reasons:

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1. Hemodynamic stability: Anesthesia can lead to hemodynamic instability, including hypotension and decreased cardiac output. Norepinephrine, as a potent vasoconstrictor and inotropic agent, can help maintain adequate blood pressure and cardiac output during surgery. It is often used as a vasopressor to treat anesthesia-induced hypotension.

2. Stress response modulation: Surgical procedures can trigger a stress response in patients, leading to an increase in catecholamines like norepinephrine. High levels of norepinephrine can cause undesirable effects such as tachycardia, hypertension, and increased myocardial oxygen demand. Anesthesiologists may use medications to blunt this stress response and reduce the release of norepinephrine, ultimately decreasing the risk of perioperative complications.

3. Pain management: Norepinephrine is involved in the modulation of pain perception. Some regional anesthesia techniques, like epidural or spinal anesthesia, can result in a reduction of norepinephrine release, which can contribute to better postoperative pain control.

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Here are the main steps in norepinephrine's mechanism of action:

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1. Binding to adrenergic receptors: Norepinephrine binds to and activates α1-, α2-, and β1-adrenergic receptors found in the smooth muscle cells of blood vessels, the heart, and other tissues.

2. Vasoconstriction: Activation of α1-adrenergic receptors on vascular smooth muscle cells leads to the activation of intracellular signaling pathways that increase intracellular calcium levels, causing the smooth muscle cells to contract. This results in vasoconstriction, which narrows the blood vessels, primarily arterioles, and increases systemic vascular resistance.

3. Cardiac effects: Norepinephrine's action on β1-adrenergic receptors in the heart increases the force of cardiac muscle contractions (positive inotropic effect) and the heart rate (positive chronotropic effect). This results in an increased cardiac output, further contributing to the elevation of blood pressure.

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                                                                                         Key points about Norepinephrine

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• Direct α1, α2 and β1 adrenergic agonist. Minimal β2 effects.

 

• Increases BP, SVR and PVR.

 

• Norepinephrine causes greater increase in SVR, MAP, SBP, and DBP than epinephrine because it has minimal β2 effects.

 

• Cardiac output may increase or decrease depending on SVR. A high afterload may decrease cardiac output.

 

• Equal in potency to epinephrine for stimulation of β1 receptors.

 

• Heart rate changes may be minimal because β1-mediated increases in HR are counteracted by baroreceptor reflexes due to arterial vasoconstriction.

 

• The major process of elimination is by reuptake into adrenergic nerve endings where it is stored for later release.

 

• Small amount is metabolized by MAO and COMT.

 

• Indicated for peripheral vascular collapse to increase SVR such as septic shock and vasoplegia after cardiopulmonary bypass.

 

• Risk of reduced organ perfusion (kidney, mesenteric, bowel, extremities).

 

• Myocardial ischemia is possible from increased afterload and HR.

 

• Phentolamine is the treatment for norepinephrine extravasation (leakage into extravascular tissue).

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