Bisoprolol

Usage

Bisoprolol is primarily prescribed for:

• Hypertension: Management of high blood pressure.
• Angina Pectoris (Chronic Stable Angina): Treatment of chest pain due to reduced blood flow to the heart.
• Heart Failure (Chronic Stable Heart Failure with Reduced Ejection Fraction HFrEF): As an adjunct to other medications (e.g., ACE inhibitors, diuretics) to improve symptoms and reduce mortality.

Pharmacological Classification: Bisoprolol is a cardioselective beta-1 adrenergic receptor blocker (beta-blocker).

Mechanism of Action: Bisoprolol selectively blocks beta-1 adrenergic receptors in the heart, reducing heart rate, myocardial contractility, and cardiac output, thus lowering blood pressure and myocardial oxygen demand.

Alternate Names

Bisoprolol is the generic name. It’s also known as bisoprolol fumarate. Brand names include Zebeta (discontinued in the US), Concor and Bisoprolol Sandoz.

How It Works

Pharmacodynamics: Bisoprolol’s primary effect is on the cardiovascular system. By selectively blocking beta-1 receptors, it reduces heart rate (negative chronotropic effect), decreases the force of heart contractions (negative inotropic effect), slows atrioventricular conduction, and suppresses renin release from the kidneys.

Pharmacokinetics:

• Absorption: Bisoprolol is well-absorbed orally (around 90%).
• Metabolism: It is metabolized in the liver, with both the parent drug and its metabolites being active.
• Elimination: Bisoprolol is eliminated approximately equally through renal and hepatic routes. Its elimination half-life is 9-12 hours.

Mode of Action: Bisoprolol competitively binds to beta-1 adrenergic receptors, preventing the binding of endogenous catecholamines (like adrenaline and noradrenaline), thereby inhibiting sympathetic stimulation of the heart.

Receptor Binding: High affinity for beta-1 receptors with much lower affinity for beta-2 receptors, making it cardioselective.

Elimination Pathways: Excreted approximately equally via the kidneys (renal) and liver (hepatic/biliary) with a half-life of 9-12 hours, allowing for once-daily dosing.

Dosage

Standard Dosage

Adults:

• Hypertension/Angina: Initial dose is typically 5 mg once daily, which can be increased to 10 mg and then to a maximum of 20 mg once daily if needed. Some patients may benefit from a starting dose of 2.5 mg.
• Heart Failure (HFrEF): Initial dose is 1.25 mg once daily, titrated gradually over several weeks as tolerated, aiming for a target maintenance dose of 10 mg once daily. Titration steps usually involve increasing the dose to 2.5 mg, 3.75 mg, 5 mg, and 7.5 mg at weekly or monthly intervals as per patient response.

Children: Safety and efficacy in children have not been established. Use is not recommended.

Special Cases:

• Elderly Patients: Start with the lowest possible dose and titrate cautiously.
• Patients with Renal Impairment: For severe renal impairment (creatinine clearance < 20 mL/min), the maximum dose is 10 mg once daily.
• Patients with Hepatic Dysfunction: For severe hepatic impairment, the maximum dose is 10 mg once daily.
• Patients with Comorbid Conditions:
  • Bronchospastic Disease (Asthma, COPD): Bisoprolol is generally not recommended, but if necessary, start with an extremely low dose (2.5 mg) and titrate cautiously with a bronchodilator readily available.
  • Diabetes: Bisoprolol can mask symptoms of hypoglycemia (e.g., tachycardia), so careful monitoring is essential.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: While beta-blockers can be beneficial in perioperative settings and ICUs, bisoprolol’s specific dosing in these situations requires careful consideration and should be individualized based on patient condition and hemodynamic stability. A single preoperative dose of 2.5mg has been shown to reduce bleeding in some surgeries.
• Emergency Situations: Bisoprolol is not typically used in acute emergency situations requiring immediate hemodynamic control.

Dosage Adjustments:

Dose adjustments are based on renal/hepatic function, other comorbid conditions, and individual patient response. Close monitoring of heart rate and blood pressure is crucial during titration. Avoid abrupt discontinuation, as this can lead to rebound hypertension or worsening of heart failure. Taper the dose gradually when discontinuing therapy.

Side Effects

Common Side Effects:

• Bradycardia
• Dizziness
• Fatigue
• Headache
• Cold extremities

Rare but Serious Side Effects:

• Worsening of heart failure
• Severe bradycardia or hypotension
• Bronchospasm (in patients with pre-existing respiratory conditions)
• Hypoglycemia (masked symptoms in diabetics)

Long-Term Effects: With prolonged use, some patients may experience worsening of pre-existing peripheral vascular disease.

Adverse Drug Reactions (ADR): Rare but serious ADRs include severe bradycardia, heart block, and bronchospasm.

Contraindications

• Acute Heart Failure:
• Decompensated Heart Failure Requiring IV Inotropic Support:
• Cardiogenic Shock:
• Severe Bradycardia or Hypotension:
• Second- or Third-Degree Atrioventricular Block (without a pacemaker):
• Sick Sinus Syndrome:
• Severe Bronchial Asthma or COPD:
• Severe Peripheral Arterial Occlusive Disease or Raynaud’s Syndrome:
• Metabolic Acidosis:
• Untreated Pheochromocytoma:

Drug Interactions

Bisoprolol can interact with various medications:

• Calcium Channel Blockers (especially verapamil and diltiazem): Can enhance bradycardia and hypotension.
• Other Antihypertensives: Additive hypotensive effects.
• Class I Antiarrhythmics (e.g., disopyramide, flecainide): Additive negative inotropic and chronotropic effects.
• Digoxin: Can increase bradycardia.
• Insulin or Oral Hypoglycemics: Can mask symptoms of hypoglycemia and potentiate their effects.
• NSAIDS: Can reduce the antihypertensive effect of bisoprolol.

Pregnancy and Breastfeeding

Bisoprolol should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is classified as FDA Pregnancy Category C.

Bisoprolol is excreted in breast milk. Caution should be exercised when administering to breastfeeding mothers. Monitor the infant for bradycardia and hypotension.

Drug Profile Summary

• Mechanism of Action: Cardioselective beta-1 blocker, reduces heart rate and blood pressure.
• Side Effects: Bradycardia, dizziness, fatigue, headache. Rarely, worsening heart failure, severe hypotension, bronchospasm.
• Contraindications: Acute or decompensated heart failure, severe bradycardia, heart block, severe asthma/COPD.
• Drug Interactions: Calcium channel blockers, other antihypertensives, Class I antiarrhythmics, digoxin, insulin/oral hypoglycemics, NSAIDS.
• Pregnancy & Breastfeeding: Use with caution. Potential fetal/neonatal risks.
• Dosage: Hypertension/angina: 5-20 mg once daily. Heart failure: 1.25 mg titrated up to 10 mg once daily.
• Monitoring Parameters: Heart rate, blood pressure, signs and symptoms of worsening heart failure (especially in at-risk patients).

Popular Combinations

Bisoprolol is often used in combination with other medications for heart failure, such as ACE inhibitors (e.g., enalapril, ramipril), diuretics (e.g., furosemide, torsemide), and sometimes digoxin or mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone).

Precautions

• Pre-existing conditions like diabetes, peripheral vascular disease, and respiratory disorders require careful monitoring.
• Bisoprolol can mask hypoglycemia symptoms, so diabetics should be vigilant.
• Caution advised for patients with hepatic or renal impairment.
• Gradual dose reduction essential upon discontinuation.
• Lifestyle modifications such as diet and exercise are recommended alongside pharmacological therapy.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Bisoprolol?

A: It depends on the indication. For hypertension/angina, it’s 5-20 mg once daily. For heart failure, it starts at 1.25 mg and is titrated up to 10 mg once daily.

Q2: How should Bisoprolol be administered?

A: Orally, once daily, preferably in the morning, with or without food.

Q3: What are the common side effects of Bisoprolol?

A: Bradycardia, dizziness, fatigue, and headache are common.

Q4: What are the contraindications to using Bisoprolol?

A: Acute heart failure, decompensated heart failure, severe bradycardia, heart block, severe asthma/COPD.

Q5: Can Bisoprolol be used in patients with asthma?

A: Generally not recommended due to the risk of bronchospasm. If necessary, use with extreme caution at very low doses and ensure a bronchodilator is available.

Q6: How should Bisoprolol be discontinued?

A: Gradually taper the dose over 1-2 weeks to avoid rebound hypertension or worsening of heart failure.

Q7: Can Bisoprolol be used during pregnancy?

A: Use with caution only if the benefit clearly outweighs the risk to the fetus.

Q8: Does Bisoprolol interact with other medications?

A: Yes, it can interact with calcium channel blockers, other antihypertensives, and other medications, so a thorough medication review is necessary.

Q9: Can Bisoprolol affect blood sugar levels?

A: It can mask symptoms of hypoglycemia, so careful monitoring is essential, especially in diabetics.

Q10: Can Bisoprolol be crushed?

A: Some brands can be broken along a score line, but consult the specific product information before crushing or chewing. Generally, it’s best to swallow the tablets whole.