What is metoprolol?

What is Metoprolol?

Metoprolol is a beta-1 selective (cardioselective) adrenergic receptor blocker used primarily to treat hypertension, angina pectoris, heart failure with reduced ejection fraction, and for secondary prevention after myocardial infarction. 1

Mechanism of Action

Metoprolol works by competitively blocking beta-1 adrenergic receptors, which are predominantly located in cardiac tissue 1. This preferential beta-1 selectivity is not absolute—at higher plasma concentrations, metoprolol also inhibits beta-2 receptors located in bronchial and vascular smooth muscle 1.

The drug's clinical effects include:

• Reduction in heart rate and cardiac output at rest and during exercise 1
• Decreased systolic blood pressure upon exertion 1
• Inhibition of catecholamine-induced increases in myocardial contractility and oxygen demand 1
• Slowing of sinus rate and AV nodal conduction 1

Available Formulations

Metoprolol exists in two distinct formulations with different pharmacokinetic profiles 2:

• Metoprolol tartrate (immediate-release): Requires twice-daily dosing, typically 25-100 mg twice daily 2
• Metoprolol succinate (extended-release/CR/XL): Allows once-daily dosing, typically 50-400 mg once daily 2

The oral bioavailability is approximately 50% due to significant first-pass hepatic metabolism, which is saturable and leads to non-proportionate increases in drug exposure with higher doses 1.

Primary Clinical Indications

Heart Failure with Reduced Ejection Fraction

Sustained-release metoprolol succinate has proven mortality benefit in chronic heart failure. 3 The MERIT-HF trial demonstrated a 34% reduction in all-cause mortality, 38% decrease in cardiovascular mortality, and 41% decrease in sudden death when metoprolol CR/XL was titrated to a target dose of 200 mg daily 3.

• Initial dosing: 12.5-25 mg once daily 2
• Target dose: 200 mg once daily 2
• Titration schedule: Increase every 2 weeks if tolerated 2

Hypertension

Metoprolol reduces blood pressure through multiple mechanisms: competitive antagonism of catecholamines at cardiac adrenergic receptors (decreasing cardiac output), central effects reducing sympathetic outflow, and suppression of renin activity 1.

• Metoprolol tartrate: 25-50 mg twice daily initially, maximum 200 mg twice daily 2
• Metoprolol succinate: 50-200 mg once daily, maximum 400 mg daily 2

Angina Pectoris

By blocking catecholamine-induced increases in heart rate, contractility, and blood pressure, metoprolol reduces myocardial oxygen requirements at any given level of effort 1.

Post-Myocardial Infarction

Metoprolol provides secondary prevention benefits after MI, though the precise mechanism remains incompletely understood 1. Early IV administration followed by oral therapy reduces reinfarction rates and ventricular fibrillation, but increases cardiogenic shock risk in high-risk patients 2.

Critical Contraindications

Absolute contraindications that preclude metoprolol use include: 2

• Decompensated heart failure or signs of low cardiac output
• Second or third-degree AV block without a functioning pacemaker
• PR interval >0.24 seconds
• Active asthma or severe reactive airway disease
• Cardiogenic shock
• Symptomatic bradycardia (heart rate <50-60 bpm with symptoms)
• Severe hypotension (systolic BP <100 mmHg with symptoms)

Pharmacokinetics and Drug Interactions

Metoprolol undergoes extensive hepatic metabolism via CYP2D6, making it subject to significant drug interactions with CYP2D6 inhibitors 1. The drug is extensively distributed with a volume of distribution of approximately 3.2-5.6 L/kg 1.

The half-life of metoprolol succinate is 3-7 hours, supporting once or twice daily dosing depending on formulation 2.

Important Clinical Distinctions

Not all beta-blockers are equivalent in heart failure. 3 Only three beta-blockers have demonstrated mortality reduction in chronic heart failure: bisoprolol, sustained-release metoprolol succinate, and carvedilol 3.

Immediate-release metoprolol tartrate showed lesser effectiveness compared to sustained-release metoprolol succinate in clinical trials 3. In the COMET trial, carvedilol demonstrated superior mortality reduction compared to immediate-release metoprolol tartrate, though this comparison used neither the dose nor formulation proven effective in MERIT-HF 3.

Common Adverse Effects

The most frequently reported side effects include: 2

• Hypotension (particularly with IV administration)
• Bradycardia (heart rate <60 bpm)
• Fatigue and dizziness
• Bronchospasm (especially in patients with reactive airway disease)

Abrupt discontinuation must be avoided, as it can precipitate severe exacerbation of angina, myocardial infarction, ventricular arrhythmias, and increased mortality risk 2.