Usage
S-Metoprolol Succinate, the S-enantiomer of metoprolol, is a cardioselective beta-1 adrenergic blocking agent primarily prescribed for:
- Hypertension: Lowers blood pressure, thus reducing risks of cardiovascular events like strokes and myocardial infarctions.
- Angina Pectoris: Reduces the frequency and severity of angina attacks.
- Heart Failure: Decreases morbidity and mortality in patients with heart failure, particularly by reducing the risk of heart failure hospitalizations.
- Myocardial Infarction (Post-MI): Reduces the risk of subsequent cardiac events and mortality after a heart attack.
Pharmacological Classification: Cardioselective Beta-1 Blocker, Antihypertensive, Antianginal.
Mechanism of Action: S-Metoprolol selectively blocks beta-1 adrenergic receptors in the heart, reducing heart rate, myocardial contractility, and cardiac output. This leads to a decrease in blood pressure and myocardial oxygen demand, providing therapeutic benefits in hypertension, angina, and heart failure.
Alternate Names
- Metoprolol succinate
- S-Isomer Metoprolol succinate
Brand Names: Toprol XL, Betaloc ZOK (and various generics)
How It Works
Pharmacodynamics: S-Metoprolol primarily affects the cardiovascular system by reducing heart rate, contractility, and cardiac output. It decreases blood pressure by reducing peripheral vascular resistance and renin release.
Pharmacokinetics:
- Absorption: Well-absorbed orally. The extended-release formulation provides slow and sustained release.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6, to inactive metabolites.
- Elimination: Excreted primarily in urine.
Mode of Action: Binds competitively to beta-1 adrenergic receptors in the heart, preventing the binding of catecholamines (norepinephrine and epinephrine). This inhibits the sympathetic stimulation of the heart, leading to the therapeutic effects.
Receptor Binding/Enzyme Inhibition: Selective beta-1 adrenergic receptor antagonist. It does not intrinsically inhibit enzymes. However, genetic polymorphisms of CYP2D6 can influence its metabolism.
Elimination Pathways: Primarily hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial 25-100 mg once daily, titrated weekly as needed. Maximum: 400 mg/day.
- Angina Pectoris: Initial 100 mg once daily, titrated weekly as needed. Maximum: 400 mg/day.
- Heart Failure: Initial 12.5 mg (severe HF) or 25 mg (NYHA Class II HF) once daily. Double every two weeks as tolerated. Maximum: 200 mg/day.
- Post-Myocardial Infarction: Initially, 5 mg IV every 2 minutes (x3 doses), followed by 50 mg orally every 6 hours for 48 hours, then 100 mg twice daily.
Children (6 years and older):
- Hypertension: Initial 1 mg/kg once daily (maximum 50 mg). Titrate as needed according to blood pressure response. Maximum: 2 mg/kg or 200 mg daily.
- Other indications: Limited data available; dosing must be determined by a physician.
Special Cases:
- Elderly Patients: Start with a low dose and titrate cautiously due to potential for reduced hepatic, renal, or cardiac function.
- Patients with Renal Impairment: No dosage adjustment is typically needed.
- Patients with Hepatic Dysfunction: Start with a low dose and titrate cautiously due to potential for reduced metabolism.
- Patients with Comorbid Conditions: Consider comorbid conditions like diabetes, asthma, or peripheral vascular disease during dose titration and monitoring.
Clinical Use Cases
Dosage adjustments for specific clinical situations (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations) should be determined on a case-by-case basis under the guidance of an experienced physician. The extended-release formulation is generally preferred for these settings due to its sustained hemodynamic effects. The immediate-release formulation or intravenous administration might be considered in acute or unstable scenarios. Specific dosing recommendations for those clinical use cases cannot be provided as they are not part of the FDA-approved labeling, and their usage should be determined by medical professionals based on individual patient conditions and clinical experience.
Dosage Adjustments
Dose modifications are based on patient response, tolerability, and comorbidities. Consider renal/hepatic function, drug interactions, and other patient-specific factors during dose titration.
Side Effects
Common Side Effects:
- Fatigue
- Dizziness
- Bradycardia
- Hypotension
- Depression
- Shortness of breath
- Diarrhea
- Nausea
- Cold extremities
Rare but Serious Side Effects:
- Worsening heart failure
- Severe bradycardia or heart block
- Bronchospasm (especially in patients with asthma or COPD)
- Anaphylactic reactions (rare)
Long-Term Effects:
- Potential for worsening pre-existing peripheral vascular disease.
- Mask symptoms of hypoglycemia in diabetic patients.
Adverse Drug Reactions (ADR):
- Angioedema
- Thrombocytopenia
- Liver injury (rare)
Contraindications
- Severe bradycardia
- Second- or third-degree heart block
- Cardiogenic shock
- Decompensated heart failure
- Sick sinus syndrome (unless a permanent pacemaker is in place)
- Hypersensitivity to metoprolol or any component of the formulation
Drug Interactions
- CYP450 Interactions: CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase metoprolol levels. CYP2D6 inducers (e.g., rifampin) can decrease metoprolol levels.
- Other Drug Interactions: Calcium channel blockers (especially verapamil and diltiazem), clonidine, digoxin, and other antihypertensives can potentiate bradycardia and hypotension.
- OTC Drugs/Supplements: Decongestants can increase blood pressure. Certain herbal supplements may interact.
- Food and Lifestyle Factors: Alcohol can enhance the hypotensive effects. Smoking may decrease its effectiveness.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA)
- Fetal Risks: Potential for fetal bradycardia, intrauterine growth retardation, and neonatal hypoglycemia. Use only if clearly needed.
- Breastfeeding: Metoprolol is excreted in breast milk in small quantities. Monitor the infant for bradycardia, hypotension, and poor feeding.
Drug Profile Summary
- Mechanism of Action: Cardioselective beta-1 blocker, reduces heart rate and contractility.
- Side Effects: Fatigue, dizziness, bradycardia, hypotension, depression.
- Contraindications: Severe bradycardia, heart block, cardiogenic shock, decompensated HF.
- Drug Interactions: Calcium channel blockers, clonidine, digoxin, CYP2D6 inhibitors.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Varies based on indication; titrate to response and tolerability.
- Monitoring Parameters: Heart rate, blood pressure, ECG, symptoms of heart failure.
Popular Combinations
- Hydrochlorothiazide: Synergistic antihypertensive effect.
- Other antihypertensives (e.g., ACE inhibitors, ARBs): Used in combination for more effective blood pressure control.
Precautions
- General Precautions: Monitor for bradycardia, hypotension, and heart failure exacerbation.
- Specific Populations: Monitor closely in elderly, patients with hepatic dysfunction, asthma/COPD, and diabetes. Use with caution in pregnancy and breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for S-Metoprolol Succinate?
A: Dosage varies depending on the indication. For hypertension, the initial dose is 25-100 mg once daily. For angina, 100 mg once daily. For heart failure, 12.5 or 25 mg once daily depending on severity. Doses are titrated as needed.
Q2: What are the common side effects?
A: Common side effects include fatigue, dizziness, bradycardia, hypotension, depression, shortness of breath, and gastrointestinal disturbances.
Q3: What are the contraindications to S-Metoprolol Succinate?
A: Contraindications include severe bradycardia, heart block, cardiogenic shock, decompensated heart failure, and sick sinus syndrome.
Q4: Can S-Metoprolol Succinate be used in pregnancy?
A: Use with caution in pregnancy only if clearly needed. It’s a Pregnancy Category C drug, meaning potential fetal risks exist.
Q5: How should S-Metoprolol Succinate be administered?
A: Administer orally once daily, preferably with or immediately after a meal.
Q6: What if a patient misses a dose?
A: Take the missed dose as soon as remembered unless it’s close to the next scheduled dose. Do not double doses.
Q7: What are the signs of an overdose?
A: Overdose symptoms include severe bradycardia, hypotension, difficulty breathing, and dizziness. Seek immediate medical attention.
Q8: Does S-Metoprolol affect blood sugar levels?
A: It can mask symptoms of hypoglycemia in diabetic patients, requiring careful monitoring.
Q9: Can S-Metoprolol Succinate be stopped abruptly?
A: No, abrupt cessation can exacerbate angina and potentially lead to myocardial infarction or arrhythmias. Taper the dose gradually under medical supervision.
Q10: What should be monitored in patients taking S-Metoprolol Succinate?
A: Closely monitor heart rate, blood pressure, ECG, and symptoms of heart failure, especially during dose titration.
