Learning Objective

By the end of this section, the student should be able to predict changes in heart rate, cardiac output, blood pressure, and mean arterial pressure produced by common sympathomimetic drugs and explain epinephrine reversal after α-blockade, a classic USMLE Step 1 concept.

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Physiologic Effects of Sympathomimetics

Sympathomimetic drugs alter vascular tone and cardiac function through varying degrees of α- and β-adrenergic receptor activation. The net hemodynamic effect depends on receptor selectivity, dose, and reflex responses.

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Norepinephrine (α₁ > α₂ > β₁)

• Vascular effects:
  Strong α₁-mediated vasoconstriction → ↑ systolic and diastolic BP → ↑ mean arterial pressure (MAP)
• Cardiac effects:
  Mild β₁ stimulation, but reflex bradycardia predominates due to baroreceptor activation
• Net effect:
  • ↑ MAP
  • ↓ or unchanged HR
  • Variable cardiac output
  • Narrowed pulse pressure

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Epinephrine (β > α at low dose; α > β at high dose)

Before α-blockade

• β₁ effects: ↑ heart rate and contractility → ↑ cardiac output
• β₂ effects: Vasodilation → ↓ diastolic BP
• α₁ effects (higher doses): Vasoconstriction → ↑ systolic BP

Net effect:

• ↑ MAP
• Widened pulse pressure (↑ systolic, ↓ diastolic)

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Activity

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Activity

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After α-blockade (Epinephrine Reversal)

• α₁ effects are blocked
• Unopposed β₂-mediated vasodilation
• ↓ peripheral resistance → ↓ MAP

📌 This is called epinephrine reversal and is highly testable on Step 1.

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Isoproterenol (β₁ = β₂, no α activity)

• β₂-mediated vasodilation: ↓ diastolic BP and ↓ MAP
• β₁-mediated cardiac stimulation: ↑ heart rate and ↑ cardiac output

Net effect:

• ↓ MAP
• ↑ HR
• ↑ CO
• Rarely used clinically

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Phenylephrine (α₁ agonist only)

• Vascular effects: Pure vasoconstriction → ↑ systolic and diastolic BP
• Cardiac effects: Reflex bradycardia
• Key concept: No β₂ activity → cannot cause epinephrine reversal

📌 After α-blockade, phenylephrine’s pressor response is suppressed but not reversed.

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High-Yield Comparison Table (Conceptual)