Nor epinephrine vs epinephrine
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norepinephrine vs epinephrine pharmacology receptor effects clinical use comparison
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Norepinephrine vs. Epinephrine
Both are endogenous catecholamines synthesized from tyrosine, and both act as neurotransmitters and hormones. Epinephrine (adrenaline) is released mainly from the adrenal medulla; norepinephrine is the primary neurotransmitter of postganglionic sympathetic neurons and is also released from the adrenal medulla in smaller amounts.
1. Structure
They differ by a single methyl group on the amine nitrogen — epinephrine has it, norepinephrine does not. This small difference produces dramatically different receptor profiles.
2. Receptor Activity
| Receptor | Norepinephrine | Epinephrine |
|---|---|---|
| α₁ (vasoconstriction) | +++ (dominant) | ++ |
| α₂ (presynaptic inhibition) | ++ | ++ |
| β₁ (heart: ↑HR, ↑contractility) | ++ | +++ |
| β₂ (vasodilation, bronchodilation) | + (weak) | +++ (strong) |
| β₃ (lipolysis/thermogenesis) | + | + |
Rank order of affinity:
- α receptors: epinephrine ≥ norepinephrine >> isoproterenol
- β₁ receptors: isoproterenol > epinephrine = norepinephrine
- β₂ receptors: isoproterenol > epinephrine >> norepinephrine
(Schwartz's Principles of Surgery, Lippincott Pharmacology)
3. Cardiovascular Effects (the key difference)
Ganong's Review of Medical Physiology, Fig 19–5: Circulatory changes during slow IV infusion in humans.
| Parameter | Norepinephrine | Epinephrine |
|---|---|---|
| Systolic BP | ↑↑ | ↑ |
| Diastolic BP | ↑↑ | ↓ (β₂ vasodilation) |
| Pulse pressure | Narrow | Widened |
| Total peripheral resistance (TPR) | ↑↑ (α₁ dominant) | ↓ (β₂ vasodilation overrides α in skeletal muscle/liver) |
| Heart rate | ↓ (reflex bradycardia from baroreceptors) | ↑ (direct β₁ + baroreceptor effect insufficient to counteract) |
| Cardiac output | ↓ or unchanged | ↑ |
Key mechanism of heart rate difference:
- Norepinephrine raises BP enough to strongly activate baroreceptors → reflex vagal bradycardia dominates its direct β₁ tachycardia.
- Epinephrine: baroreceptor stimulation is insufficient to obscure the direct β₁ effect → net tachycardia and increased cardiac output.
4. Other Systemic Effects
| Effect | Norepinephrine | Epinephrine |
|---|---|---|
| Bronchial smooth muscle | Minimal (weak β₂) | Bronchodilation (strong β₂) |
| Blood glucose | Glycogenolysis (moderate) | Marked hyperglycemia (β₂ glycogenolysis in liver + ↑glucagon + ↓insulin via α₂) |
| Metabolic rate | ↑ | ↑↑ |
| CNS | Alertness | Alertness + more anxiety/fear |
| Mast cell mediator release | — | Inhibits histamine release |
5. Clinical Uses
| Indication | Drug of Choice | Rationale |
|---|---|---|
| Septic shock (first-line vasopressor) | Norepinephrine | Potent α₁ → ↑SVR → ↑MAP; also has β₁ inotropic support |
| Anaphylaxis | Epinephrine | α₁ (vasoconstriction), β₁ (↑HR/contractility), β₂ (bronchodilation + mast cell inhibition) — reverses all anaphylaxis mechanisms |
| Cardiac arrest (ACLS) | Epinephrine | Restores cardiac rhythm; β₁ + α₁ effects |
| Bronchospasm/asthma emergency | Epinephrine (or selective β₂ agents) | Strong β₂ bronchodilation |
| Adjunct to local anesthesia | Epinephrine | Vasoconstriction prolongs block, reduces systemic absorption |
| Post-cardiac arrest shock | Norepinephrine preferred | Lower re-arrest risk vs. epinephrine (recent meta-analysis) |
Harrison's (2025): "Norepinephrine is the first-choice vasopressor in septic shock... At higher doses, epinephrine has a similar profile... Vasopressin should be added as a second agent, and epinephrine as a third agent."
6. Pharmacokinetics
Both are rapidly metabolized by MAO and COMT → metabolites (metanephrine, normetanephrine, VMA) excreted in urine. Both have a very short duration of action and are given as IV infusions in acute settings.
7. Adverse Effects
| Effect | Norepinephrine | Epinephrine |
|---|---|---|
| Arrhythmias/angina | Yes | Yes (more pronounced) |
| Hypertension | Yes (dominant) | Yes |
| Tissue necrosis on extravasation | Yes — significant risk (treat with phentolamine or topical nitroglycerin) | Less prominent |
| Anxiety/tremor | Less | More |
| Hyperglycemia | Moderate | More marked |
| Pulmonary edema | Less | Yes (↑afterload) |
Quick Memory Hook
Norepinephrine = mostly α → Narrows vessels, No β₂ bronchodilation, Net bradycardia (reflex). Epinephrine = α + strong β → Elevates heart rate and output, Expands bronchi, Essential for anaphylaxis.
Sources: Lippincott Illustrated Reviews: Pharmacology; Ganong's Review of Medical Physiology; Basic Medical Biochemistry (Lieberman); Harrison's Principles of Internal Medicine 22e; Rosen's Emergency Medicine; Goldman-Cecil Medicine.
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