What is the difference between epinephrine, norepinephrine and isoproterenol?💉💉💉

Have you played some survival video games? In these games, epinephrine (also call adrenaline) is often an emergency medicine. It can bring your character back to life. And it will also strengthen your character's state like a stimulant. In reality, adrenaline is also a commonly used emergency medicine in clinical practice. And there are two more medicines which are also adrenaline agonists. They are norepinephrine and isoproterenol. All of them can act directly on adrenergic receptors and activates them to produce therapeutic effects. What is the difference between the chemical structure, mechanism of action, strength of action, and clinical application of these three drugs?

1. Chemical structure

Adrenaline, norepinephrine and isoproterenol all contain phenolic hydroxyl groups, which are easily deteriorated by sunlight or in contact with air. Therefore, they need to be stored in a sealed, protected from light and cool place (below 20°C).

Epinephrine

Norepinephrine

Isoproterenol

Compared with the structure of norepinephrine, there is a methyl group on the amino nitrogen of adrenaline, and an isopropyl group on the amino nitrogen of isoproterenol.

Commonly used injections: Epinephrine 1ml : 1mg, Norepinephrine 1ml : 2mg, Isoproterenol 2ml : 1mg.

2. Mechanism

Adrenergic receptors can be divided into two types: α and β. Among them, α-adrenergic receptors have α1 and α2, and β-adrenergic receptors have β1, β2, and β3. They are distributed differently in various organs and have different effects. Adrenergic agonists are used as first aid drugs, mainly acting on α1, α2, β1 and β2 (β3-adrenergic receptor are mainly related to lipolysis). The activation of α1-adrenergic receptor will cause vascular smooth muscle to contract, which has the effect of raising blood pressure. α2-adrenergic receptor will produce feedback inhibition and will reduce the self-release of norepinephrine. In the market, α2-adrenergic receptor agonists (such as Clonidine) can treat high blood pressure. β1-adrenergic receptor are mainly distributed in the heart. Activation of it can increase the contractility and heartbeat of the heart. β2-adrenergic receptor mainly relax the smooth muscles of bronchial and skeletal muscle blood vessels. 

Epinephrine acts on α1, α2, β1 and β2 receptors. Norepinephrine acts on α1, α2 and β1 receptors. Isoproterenol acts on β1 and β2 receptors and has no obvious effect on α-receptor. 

• The ability to raise blood pressure: norepinephrine> epinephrine (its ability to relax skeletal muscle blood vessels is stronger than norepinephrine)> isoproterenol (It has no effect on the α-receptor.).
• Effect on heart rate: isoproterenol> epinephrine> norepinephrine (The effect of norepinephrine on β1-receptor is weaker than that of epinephrine).
• The effect on the bronchus: epinephrine ≈ isoproterenol> norepinephrine.

3. Clinical application

Cardiogenic shock, septic shock and shock due to hypovolemia

Norepinephrine mainly acts on α-receptors. It has a slight effect on heart β1-receptors and has almost no effect on β2-receptors. Compared with epinephrine, its vasoconstriction effect is better and it reflexively causes the heart rate to slow down. Therefore, norepinephrine is recommended for cardiogenic shock, septic shock, and shock caused by hypovolemia.

Because norepinephrine has a strong vasoconstriction effect. It is also used for non-varices upper gastrointestinal bleeding. 

Cardiac arrest

The effect on the heart β1 receptor: isoproterenol ≈ adrenaline. But the recommended drug is adrenaline. Main reason: Studies have confirmed that isoproterenol can cause myocardial inflammatory swelling and focal infarction.

Anaphylactic shock

The effect on bronchial smooth muscle β2 receptor: isoproterenol ≈ adrenaline. However, isoproterenol has a low affinity for α-receptors.

Adrenaline stimulates α-receptors and constricts blood vessels. It can raise blood pressure in patients with anaphylactic shock and eliminate bronchial mucosal edema. Adrenaline can also stimulate β2-receptors, which can expand bronchial smooth muscle. 

Therefore, epinephrine is recommended as the first choice.

• Note: Epinephrine can contract skin, mucous membrane blood vessels and expand skeletal muscle blood vessels. Subcutaneous injection of epinephrine is slower than intramuscular injection.

Complete atrioventricular block

Isoproterenol has a high affinity for heart β1-receptors. Compared with epinephrine, isoproterenol has a stronger effect on accelerating heart rate and accelerating conduction, but has a weaker effect on ectopic pacemaker. Therefore, the chance of causing arrhythmia is less than adrenaline. 

Isoproterenol is recommended for patients with complete atrioventricular block.