What is the mechanism of action of metoprolol (beta-blocker)?

Mechanism of Action of Metoprolol Tartrate

Metoprolol tartrate is a beta-1 selective (cardioselective) adrenergic receptor blocker that competitively blocks the effects of catecholamines on cell membrane beta receptors, primarily in the myocardium, reducing heart rate, contractility, and blood pressure. 1

Primary Mechanism of Action

Metoprolol works through several key mechanisms:

1. Beta-1 Receptor Selectivity

   • Selectively blocks beta-1 adrenergic receptors located primarily in the myocardium
   • At higher doses, this selectivity is not absolute and can also inhibit beta-2 receptors in bronchial and vascular musculature 1

2. Cardiovascular Effects

   • Reduces heart rate at rest and during exercise
   • Decreases cardiac output
   • Reduces systolic blood pressure, especially during exercise
   • Inhibits isoproterenol-induced tachycardia
   • Reduces reflex orthostatic tachycardia 1

3. Antihypertensive Mechanism Several proposed mechanisms contribute to blood pressure reduction:

   • Competitive antagonism of catecholamines at cardiac adrenergic neuron sites
   • Central effects leading to reduced sympathetic outflow
   • Suppression of renin activity 1

Clinical Effects

Metoprolol produces several measurable physiological changes:

• Heart Failure: Blocks the deleterious effects of chronic sympathetic nervous system activation, which initially supports the failing heart but long-term leads to adverse effects 2
• Cardiac Remodeling: Long-term administration reverses changes associated with left ventricular remodeling, decreases myocardial mass and left ventricular volume 2
• Electrophysiological Effects: Slows sinus rate and decreases AV nodal conduction 1
• Hemodynamic Effects: In myocardial infarction patients, causes reduction in heart rate, systolic blood pressure, and cardiac output 1

Differences from Non-Selective Beta Blockers

Metoprolol's beta-1 selectivity is demonstrated by:

• Less effect on FEV₁ and FVC in asthmatic patients compared to non-selective beta blockers
• Inability to reverse beta-2 mediated vasodilating effects of epinephrine 1

Important Clinical Considerations

• No Intrinsic Sympathomimetic Activity: Metoprolol lacks intrinsic sympathomimetic activity 1
• Membrane Stabilization: Only detectable at doses much higher than required for beta-blockade 1
• Pharmacokinetics: Has approximately 50% oral bioavailability due to pre-systemic metabolism 1
• Duration of Effect: Longer than expected from its half-life, making it suitable for twice daily administration in hypertension 3

Cautions and Considerations

• Withdrawal Phenomena: Abrupt discontinuation can lead to rebound increases in cardiac chronotropic sensitivity to isoproterenol and resting heart rate 4
• Formulation Differences: Sustained-release metoprolol (succinate) has been shown to be more effective than immediate-release metoprolol (tartrate) in reducing mortality in heart failure patients 2
• Comparison with Other Beta Blockers: In heart failure, carvedilol has shown greater mortality reduction compared to immediate-release metoprolol tartrate, though comparisons with sustained-release formulations are lacking 2

Metoprolol's cardioselectivity makes it particularly useful in patients who might not tolerate non-selective beta blockade, though this selectivity diminishes at higher doses.