U01.05.023 Sympathomimetics

Sympathomimetics are drugs that mimic the effects of the sympathetic nervous system by stimulating adrenergic receptors. These can be classified into direct and indirect sympathomimetics based on their mechanism of action.

Direct Sympathomimetics

These drugs directly bind to adrenergic receptors, producing receptor-specific effects.

Drug Actions, Hemodynamic Changes, and Clinical Applications

Drug	Receptor Selectivity	Hemodynamic Effects	Clinical Applications
Albuterol, Salmeterol, Terbutaline	β2 > β1	Minimal effect on HR	– Albuterol: Acute asthma/COPD. – Salmeterol: Long-term asthma/COPD. – Terbutaline: Acute bronchospasm in asthma, tocolysis.
Dobutamine	β1 > β2, α	/ BP, ↑ HR, ↑ CO	– Heart failure (inotropic > chronotropic). – Cardiogenic shock. – Cardiac stress testing.
Dopamine	D1 = D2 > β > α	↑ BP (high dose), ↑ HR, ↑ CO	– Unstable bradycardia. – Heart failure. – Shock. – Vasoconstriction at high doses (α effects).
Epinephrine	β > α	↑ BP (high dose), ↑ HR, ↑ CO	– Anaphylaxis. – Asthma. – Open-angle glaucoma. – Strong β2 effect compared to norepinephrine.
Fenoldopam	D1	↓ BP (vasodilation), ↑ HR, ↑ CO	– Postoperative hypertension. – Hypertensive crisis. – Promotes natriuresis.
Isoproterenol	β1 = β2	↓ BP (vasodilation), ↑ HR, ↑ CO	– Electrophysiologic evaluation of tachyarrhythmias. – Can worsen ischemia.
Midodrine	α1	↑ BP (vasoconstriction), ↓ HR, / CO	– Autonomic insufficiency. – Postural hypotension. – May worsen supine hypertension.
Mirabegron	β3	Not significant	– Urinary urgency, incontinence, or overactive bladder.
Norepinephrine	α1 > α2 > β1	↑ BP, ↑ HR, / CO	– Hypotension. – Septic shock.
Phenylephrine	α1 > α2	↑ BP (vasoconstriction), ↓ HR, / CO	– Hypotension. – Ocular procedures (mydriatic). – Rhinitis (decongestant). – Ischemic priapism.

Indirect Sympathomimetics

These drugs act by increasing the release of endogenous catecholamines or inhibiting their reuptake.

Drug	Mechanism of Action	Clinical Applications
Amphetamine	Indirect general agonist, reuptake inhibitor; releases stored catecholamines	– Narcolepsy. – Obesity. – ADHD.
Cocaine	Indirect general agonist, reuptake inhibitor	– Local anesthesia. – Vasoconstriction. Caution: Avoid β-blockers to prevent unopposed α1 activation, which can cause extreme hypertension.
Ephedrine	Indirect general agonist, releases stored catecholamines	– Nasal decongestion (pseudoephedrine). – Urinary incontinence. – Hypotension.

Key Points to Remember

Receptor Selectivity Matters: The clinical effects depend on the receptor subtype targeted by the drug.
Indirect Mechanisms: Drugs like cocaine and amphetamines act by increasing endogenous catecholamines.
Cautions:
- Epinephrine: Strong β2 effect at low doses; α effects predominate at high doses.
- Cocaine: Avoid β-blockers to prevent severe hypertension.
Applications Tailored to Hemodynamics: Choose drugs based on specific cardiovascular or respiratory needs (e.g., dobutamine for inotropic support).

Bibliography Reference Links

First Aid for the USMLE Step 1 2024.
NCBI: Sympathomimetic Agents
Pharmacology Simplified

USMLE Step 1 Review Series

Curriculum