Learning Objective

By the end of this section, students should be able to classify sympathomimetic drugs, identify their receptor selectivity, predict their hemodynamic effects, and select the appropriate clinical application in common Step 1 scenarios.

Sympathomimetic Drugs

Sympathomimetics are agents that stimulate adrenergic receptors either directly or indirectly, producing cardiovascular, pulmonary, and metabolic effects. Their clinical use depends on receptor selectivity, dose, and route of administration.

Direct Sympathomimetics

β₂-Selective Agonists

Albuterol, Salmeterol, Terbutaline (β₂ > β₁)

Hemodynamic effects: Minimal ↑ HR
Primary actions: Bronchodilation, uterine relaxation
Clinical uses:
- Albuterol: Acute asthma/COPD exacerbations
- Salmeterol: Long-term (maintenance) asthma/COPD
- Terbutaline: Acute bronchospasm, tocolysis

β₁-Selective Agonist

Dobutamine (β₁ > β₂)

Hemodynamic effects: ↑ HR, ↑ contractility, ↑ cardiac output; BP unchanged or ↓
Clinical uses:
- Cardiac stress testing
- Acute decompensated heart failure with cardiogenic shock
Key concept: Pure inotrope

Mixed Dopamine Receptor Agonist

Dopamine (D₁ = D₂ > β > α)

Dose-dependent effects:
- Low dose: Renal vasodilation (D₁)
- Medium dose: ↑ HR, ↑ CO (β₁)
- High dose: Vasoconstriction, ↑ BP (α₁)
Clinical uses: Shock, unstable bradycardia

Mixed α and β Agonists

Epinephrine (β > α)

Hemodynamic effects: ↑ HR, ↑ CO; ↑ BP at high doses
Clinical uses:
- Anaphylaxis
- Asthma
- Shock
Key concept: Stronger β₂ effect than norepinephrine

Norepinephrine (α₁ > α₂ > β₁)

Hemodynamic effects: ↑ BP, minimal or reflex ↓ HR, variable CO
Clinical uses: Septic shock, severe hypotension

Selective Vasodilators

Fenoldopam (D₁ agonist)

Hemodynamic effects: Vasodilation → ↓ BP, ↑ HR, ↑ CO
Clinical uses: Hypertensive emergencies
Additional effects: Natriuresis
Adverse effects: Headache, flushing, hypotension

Pure β Agonist

Isoproterenol (β₁ = β₂)

Hemodynamic effects: ↓ BP (vasodilation), ↑ HR, ↑ CO
Clinical uses: Electrophysiologic testing for arrhythmias
Note: No α activity → may worsen ischemia

α₁-Selective Agonists

Phenylephrine (α₁ > α₂)

Hemodynamic effects: ↑ BP, reflex ↓ HR, ↓ or unchanged CO
Clinical uses:
- Hypotension
- Nasal decongestion
- Mydriasis
- Ischemic priapism

Midodrine (α₁)

Hemodynamic effects: ↑ BP, ↓ HR
Clinical uses: Orthostatic hypotension
Caution: Supine hypertension

β₃-Selective Agonist

Mirabegron (β₃)

Primary effect: Bladder relaxation
Clinical use: Overactive bladder
Mnemonic: “Mirab3gron”

Indirect Sympathomimetics

These agents increase endogenous catecholamines by promoting release or inhibiting reuptake.

Amphetamine

Mechanism: Increases release + inhibits reuptake of catecholamines
Clinical uses: ADHD, narcolepsy, obesity

Cocaine

Mechanism: Reuptake inhibition of NE, dopamine, serotonin
Effects: Vasoconstriction, local anesthesia
Key warning: Avoid β-blockers → unopposed α₁ stimulation
Special use: Produces mydriasis in intact sympathetic innervation (Horner syndrome testing)