Usage
Metoprolol Tartrate is prescribed for:
- Hypertension: Managing high blood pressure, often in combination with other antihypertensives.
- Angina Pectoris: Long-term prevention of angina attacks (chest pain).
- Myocardial Infarction: Treatment and prevention of heart attacks, both in the acute phase and for long-term management.
- Heart Failure: Managing stable, symptomatic heart failure.
- Cardiac Arrhythmias: Controlling certain types of irregular heartbeats.
- Hyperthyroidism: As an adjunctive therapy to manage symptoms.
- Migraine Prevention: Prophylactic treatment to reduce the frequency and severity of migraine headaches.
- Other conditions such as anxiety, tremors and alcohol withdrawal.
Pharmacological Classification: Metoprolol is classified as a beta-adrenergic blocking agent, specifically a selective beta-1 blocker (cardioselective). At higher doses, the selectivity for beta-1 receptors decreases.
Mechanism of Action: Metoprolol primarily blocks beta-1 adrenergic receptors located in the heart. This action reduces heart rate, myocardial contractility, and cardiac output, thereby lowering blood pressure and reducing the workload on the heart.
Alternate Names
International and Regional Variations: The generic name “metoprolol tartrate” is widely recognized.
Brand Names: Lopressor is a common brand name for the immediate-release formulation of metoprolol tartrate.
How It Works
Pharmacodynamics: Metoprolol’s primary effect is on the cardiovascular system. It reduces heart rate, myocardial contractility, and cardiac output. This leads to a decrease in blood pressure and myocardial oxygen demand.
Pharmacokinetics:
- Absorption: Metoprolol tartrate is rapidly and almost completely absorbed after oral administration. The presence of food may enhance bioavailability.
- Metabolism: It undergoes extensive first-pass metabolism in the liver, primarily by the CYP2D6 enzyme. This results in significant interindividual variability in plasma concentrations.
- Elimination: Metoprolol and its metabolites are primarily eliminated by the kidneys.
Mode of Action: Metoprolol competitively binds to beta-1 adrenergic receptors in the heart, preventing the binding of catecholamines (such as adrenaline and noradrenaline). This inhibits the sympathetic stimulation of the heart, leading to the observed cardiovascular effects.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Metoprolol is a competitive antagonist at beta-1 adrenergic receptors. It does not have significant intrinsic sympathomimetic activity.
Elimination Pathways: Primarily renal excretion of metabolites. Some hepatic metabolism via CYP2D6.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 100 mg per day, given in single or divided doses. The dose can be increased at weekly (or longer) intervals up to a maximum of 450 mg per day for immediate-release tablets and 400 mg per day for extended-release formulations.
- Angina Pectoris: Initial dose of immediate-release metoprolol tartrate is 50 mg twice daily. For extended-release, 100 mg once daily. May be increased weekly up to 400 mg per day.
- Myocardial Infarction (Early Treatment): 5 mg IV every 2 minutes for three doses, followed by 50 mg orally every 6 hours for 48 hours. Transition to 100 mg twice daily for maintenance.
Children:
- Hypertension (Extended-release formulation only): For children 6 years and older, the initial dose is 1 mg/kg once daily (maximum 50 mg). May be increased to a maximum of 2 mg/kg (or 200 mg) once daily. Immediate-release tablets are not recommended for children.
- Other indications: Use and dose must be determined by a doctor.
Special Cases:
- Elderly Patients: Initiate with a low dose and titrate cautiously.
- Patients with Renal Impairment: No dosage adjustment is typically needed.
- Patients with Hepatic Dysfunction: Start with low doses and titrate very carefully due to increased risk of adverse effects.
- Patients with Comorbid Conditions: Individualized dosing is essential. Close monitoring is required, especially in patients with diabetes, other cardiovascular diseases, or respiratory conditions.
Clinical Use Cases
Dosing for these cases should be individualized based on patient status, hemodynamics, and co-existing medical conditions. Consult specialized resources and institutional protocols for specific guidance.
- Intubation: Premedication with metoprolol may be considered to attenuate the hemodynamic response. Dosage needs careful titration.
- Surgical Procedures: Metoprolol may be used perioperatively to manage blood pressure and heart rate.
- Mechanical Ventilation: Use with caution due to potential for bradycardia and hypotension.
- Intensive Care Unit (ICU) Use: Dosing is highly patient-specific. Continuous hemodynamic monitoring is crucial.
- Emergency Situations: IV administration is preferred for rapid control of heart rate and blood pressure in situations like hypertensive emergencies.
Dosage Adjustments
- Dosage adjustments are based on patient response, tolerability, and renal/hepatic function.
- CYP2D6 genetic polymorphisms can influence metoprolol metabolism, potentially requiring dose adjustments. Slow metabolizers are at increased risk of side effects with standard doses.
Side Effects
Common Side Effects:
- Dizziness, fatigue, bradycardia, hypotension, nausea, diarrhea, constipation, shortness of breath, cold hands and feet.
Rare but Serious Side Effects:
- Worsening heart failure, severe bradycardia or heart block, bronchospasm, Raynaud’s phenomenon.
Long-Term Effects:
- Some studies suggest potential long-term risks like weight gain, sexual dysfunction. Close monitoring is advised.
Adverse Drug Reactions (ADR):
- Severe hypotension, bronchospasm, heart block.
Contraindications
- Absolute: Severe bradycardia, second- or third-degree heart block (without a pacemaker), cardiogenic shock, decompensated heart failure, sick sinus syndrome, severe peripheral artery disease.
- Relative: Asthma or chronic obstructive pulmonary disease, Prinzmetal’s angina.
Drug Interactions
Metoprolol interacts with numerous medications. Consult a comprehensive drug interaction resource. Some clinically significant interactions include:
- CYP450 Inhibitors: Fluoxetine, paroxetine, and other CYP2D6 inhibitors can increase metoprolol levels.
- CYP450 Inducers: Rifampin, phenytoin, and other CYP2D6 inducers can reduce metoprolol levels.
- Calcium Channel Blockers: Verapamil and diltiazem can enhance bradycardia and hypotension.
- Digoxin: Can increase the risk of bradycardia.
- Clonidine: Concurrent use may increase rebound hypertension upon discontinuation.
- Insulin and oral hypoglycemic agents: Metoprolol can mask the symptoms of hypoglycemia and prolong its effects.
- MAO inhibitors: May result in severe hypertension.
- Alcohol, smoking, grapefruit juice: Consumption can be detrimental and potentially dangerous when used concomitantly.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA). Metoprolol crosses the placenta. Use only if clearly needed and with careful monitoring. Potential fetal risks include bradycardia, intrauterine growth restriction.
- Breastfeeding: Metoprolol is excreted in breast milk. While generally considered safe, monitor infants for potential side effects such as bradycardia.
Drug Profile Summary
- Mechanism of Action: Beta-1 adrenergic receptor blocker.
- Side Effects: Dizziness, fatigue, bradycardia, hypotension, nausea.
- Contraindications: Severe bradycardia, heart block, decompensated heart failure.
- Drug Interactions: CYP2D6 inhibitors/inducers, calcium channel blockers, digoxin.
- Pregnancy & Breastfeeding: Use with caution; monitor for fetal/infant bradycardia.
- Dosage: Hypertension: 100-450 mg/day; Angina: 100-400 mg/day.
- Monitoring Parameters: Heart rate, blood pressure, ECG.
Popular Combinations
- Hydrochlorothiazide or other thiazide diuretics: Synergistic antihypertensive effect.
- Other antihypertensives (e.g., ACE inhibitors, ARBs, calcium channel blockers): Used in combination for additive blood pressure control.
Precautions
- General: Monitor heart rate, blood pressure, and ECG. Assess for respiratory conditions and peripheral vascular disease.
- Specific Populations: See Dosage - Special Cases.
- Lifestyle: Alcohol may increase side effects. Smoking can reduce efficacy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Metoprolol Tartrate?
A: The dosage is individualized. For hypertension, the starting dose is typically 100 mg daily, which can be increased up to 450 mg/day. For angina, the starting dose is 50 mg twice daily (immediate-release) or 100 mg once daily (extended-release), up to 400 mg/day.
Q2: How should Metoprolol Tartrate be administered?
A: Orally, with or immediately following meals. Extended-release formulations should be swallowed whole and not crushed or chewed.
Q3: What are the most common side effects of Metoprolol?
A: Dizziness, fatigue, bradycardia, and hypotension are common.
Q4: Can Metoprolol be used in patients with asthma?
A: Use with extreme caution as it can exacerbate bronchospasm. Cardioselective beta-blockers like metoprolol are generally preferred over non-selective ones if a beta-blocker is necessary.
Q5: What are the contraindications to Metoprolol use?
A: Severe bradycardia, second- or third-degree heart block, cardiogenic shock, and decompensated heart failure.
Q6: Does Metoprolol interact with other medications?
A: Yes, numerous drug interactions exist. Inform patients to disclose all medications, supplements, and herbal products they are taking.
Q7: Can Metoprolol be used during pregnancy and breastfeeding?
A: Use with caution if benefits outweigh risks. Monitor for fetal/infant bradycardia.
Q8: What should patients be advised about Metoprolol?
A: Do not discontinue abruptly. Report any side effects. Monitor blood pressure and heart rate regularly. Avoid alcohol.
Q9: How does Metoprolol affect blood sugar levels?
A: Metoprolol can mask the symptoms of hypoglycemia and potentially prolong its effects. Careful blood glucose monitoring is especially important in diabetic patients.
Q10: Can Metoprolol worsen heart failure?
A: It can initially worsen heart failure symptoms in some patients, especially during dose titration. Careful monitoring and dose adjustment are crucial. However, it is beneficial in chronic stable heart failure.
