Metoprolol - Drug Monograph

Introduction

Metoprolol is a selective beta-1 adrenergic receptor blocking agent belonging to the class of medications known as beta-blockers. It is widely prescribed for cardiovascular conditions including hypertension, angina pectoris, heart failure, and following myocardial infarction. Available in both immediate-release (metoprolol tartrate) and extended-release (metoprolol succinate) formulations, it represents one of the most commonly utilized beta-blockers in clinical practice.

Mechanism of Action

Metoprolol competitively blocks beta-1 adrenergic receptors in the heart and vascular smooth muscle. This inhibition results in:

• Reduced heart rate (negative chronotropy)
• Decreased myocardial contractility (negative inotropy)
• Slowed atrioventricular conduction
• Reduced cardiac output
• Decreased renin release from the kidneys

The selective beta-1 blockade at therapeutic doses produces these cardiovascular effects while minimizing impact on beta-2 receptors in the lungs and vascular system.

Indications

• Hypertension (monotherapy or combination therapy)
• Angina pectoris
• Heart failure (NYHA Class II-III, stable patients, using extended-release formulation)
• Secondary prevention following myocardial infarction

• Supraventricular tachycardia
• Atrial fibrillation/flutter rate control
• Migraine prophylaxis
• Essential tremor
• Symptomatic treatment in hyperthyroidism

Dosage and Administration

• Immediate-release: 50-100 mg twice daily (max: 450 mg/day)
• Extended-release: 50-100 mg once daily (max: 400 mg/day)

• Immediate-release: 50-100 mg twice daily (max: 400 mg/day)
• Extended-release: 100 mg once daily (max: 400 mg/day)

• Extended-release: Start 12.5-25 mg once daily, titrate to target 200 mg once daily

• Immediate-release: 50 mg every 6 hours for 48 hours, then 100 mg twice daily

• Hepatic impairment: Use caution; consider reduced doses
• Renal impairment: No dosage adjustment typically needed
• Geriatric: Start with lower doses due to increased sensitivity
• Pediatric: Safety not established for children

Pharmacokinetics

Contraindications

• Severe bradycardia (heart rate <45 bpm)
• Second- or third-degree heart block (without pacemaker)
• Cardiogenic shock
• Decompensated heart failure
• Sick sinus syndrome (without pacemaker)
• Severe peripheral arterial disease
• Hypersensitivity to metoprolol or related compounds
• Pheochromocytoma (without alpha-blockade)

Warnings and Precautions

• Cardiac effects: May precipitate heart failure in susceptible patients
• Bronchospasm: Use caution in patients with asthma/COPD due to potential beta-2 effects
• Hypoglycemia: May mask signs of hypoglycemia in diabetics
• Peripheral vascular disease: May exacerbate symptoms
• Thyrotoxicosis: May mask clinical signs
• Major surgery: Consider withdrawal 24-48 hours preoperatively
• Anaphylaxis: May impair response to epinephrine

Drug Interactions

• CYP2D6 inhibitors: Fluoxetine, paroxetine, quinidine (increase metoprolol levels)
• Other beta-blockers: Additive effects
• Calcium channel blockers: Verapamil, diltiazem (additive bradycardia/AV block)
• Digoxin: Additive bradycardia
• Antiarrhythmics: Disopyramide, flecainide (negative inotropic effects)
• Clonidine: Rebound hypertension with concurrent use
• NSAIDs: May decrease antihypertensive effect

Adverse Effects

• Fatigue
• Dizziness
• Depression
• Bradycardia
• Diarrhea
• Dyspnea
• Cold extremities

• AV block
• Bronchospasm
• Heart failure exacerbation
• Hypotension
• Hepatotoxicity
• Raynaud's phenomenon
• Psychiatric effects (vivid dreams, hallucinations)
• Thrombocytopenia

Monitoring Parameters

• Heart rate, blood pressure
• ECG (assess conduction abnormalities)
• Renal and hepatic function
• Assessment for heart failure symptoms

• Blood pressure at each visit
• Heart rate regularly
• Signs/symptoms of heart failure
• Weight monitoring (in heart failure patients)
• Blood glucose in diabetics
• Mental status changes

• Hypertension: BP <140/90 mmHg (individualized)
• Heart failure: Resting heart rate 50-60 bpm
• Angina: Reduced frequency of attacks

Patient Education

• Do not abruptly stop medication; taper under medical supervision
• Take with food to increase bioavailability
• Extended-release tablets should be swallowed whole, not crushed or chewed
• Monitor pulse rate regularly; report rates below 50 bpm
• Rise slowly from sitting/lying position to prevent dizziness
• Report signs of heart failure (weight gain, edema, shortness of breath)
• Inform all healthcare providers about metoprolol use
• Use caution with alcohol and other medications
• Diabetics: Be aware metoprolol may mask hypoglycemia symptoms
• Notify physician if planning pregnancy or becoming pregnant

References

1. Frishman WH. Metoprolol: a new β-adrenergic receptor blocking agent. Am J Cardiol. 1979;44(1):171-175. 2. The MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001-2007. 3. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248. 4. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2017;70(6):776-803. 5. Metoprolol prescribing information. FDA.gov. 6. Johnson JA, Burlew BS. Metoprolol metabolism via cytochrome P4502D6 in ethnic populations. Drug Metab Dispos. 1996;24(3):350-355. 7. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996;334(21):1349-1355.