Propranolol

Usage

Propranolol is a non-selective beta-adrenergic blocking agent prescribed for various medical conditions, including:

• Hypertension: Management of high blood pressure.
• Angina Pectoris: Prevention of chest pain caused by reduced blood flow to the heart.
• Cardiac Arrhythmias: Treatment of irregular heartbeats.
• Migraine Prophylaxis: Prevention of migraine headaches.
• Myocardial Infarction (Post-MI): Reduction of cardiovascular mortality after a heart attack.
• Essential Tremor: Treatment of involuntary shaking.
• Hypertrophic Subaortic Stenosis: Treatment of a heart muscle disease that makes it hard for the heart to pump blood.
• Pheochromocytoma (Adjunctive Therapy): Used in combination with alpha-blockers to control blood pressure and symptoms caused by tumors of the adrenal glands.
• Thyrotoxicosis: Management of an overactive thyroid gland.
• Anxiety: Relief of anxiety symptoms.
• Proliferating Infantile Hemangioma: Treatment of a common vascular birthmark in infants.
• Tetralogy of Fallot: Management of a congenital heart defect.
• Prophylaxis of Variceal Bleeding in Portal Hypertension: Prevention of bleeding from swollen veins in the esophagus and stomach.

Pharmacological Classification: Non-selective beta-blocker, antihypertensive, antianginal, antiarrhythmic, antimigraine.

Mechanism of Action: Propranolol competitively blocks beta-adrenergic receptors in the heart and other organs. This action reduces heart rate, myocardial contractility, and cardiac output, leading to lower blood pressure and decreased myocardial oxygen demand. Propranolol’s effects on the central nervous system contribute to its anti-anxiety and migraine prophylaxis effects.

Alternate Names

Generic Name: Propranolol hydrochloride

Brand Names: Inderal, Inderal LA, InnoPran XL, Hemangeol (for infantile hemangiomas)

How It Works

Pharmacodynamics: Propranolol’s primary action is blocking beta-1 and beta-2 adrenergic receptors. Blocking beta-1 receptors decreases heart rate and myocardial contractility, while beta-2 blockade can lead to bronchoconstriction and peripheral vasoconstriction. Propranolol also has membrane stabilizing activity at high doses.

Pharmacokinetics:

• Absorption: Well-absorbed orally, but undergoes extensive first-pass metabolism in the liver, resulting in variable bioavailability.
• Metabolism: Primarily metabolized in the liver, with 4-hydroxypropranolol being a major active metabolite.
• Elimination: Excreted primarily via the kidneys and bile, with a half-life of 3-6 hours for conventional formulations and longer for extended-release versions.

Mode of Action: Competitive antagonism at beta-adrenergic receptors reduces sympathetic stimulation of the heart. This results in decreased cAMP production, reduced calcium influx into cardiac cells, and consequently, decreased heart rate and contractility.

Receptor Binding: Binds non-selectively to both beta-1 and beta-2 adrenergic receptors.

Enzyme Inhibition/Neurotransmitter Modulation: No significant direct enzyme inhibition or neurotransmitter modulation. The therapeutic effect is achieved by reducing the effects of catecholamines (epinephrine and norepinephrine) on beta receptors.

Elimination Pathways: Primarily hepatic metabolism, with renal and biliary excretion of metabolites. Metabolism is primarily by CYP2D6, 1A2, and 2C19 enzymes.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial 40 mg twice daily, increased gradually to 120-240 mg daily. Extended-release: 80 mg once daily, increased to 120-160 mg once daily. Max: 640 mg/day.
• Angina Pectoris: 80-320 mg daily in divided doses. Extended-release: 80 mg once daily, titrated up to 320 mg as needed.
• Arrhythmias: 10-30 mg three or four times daily.
• Migraine Prophylaxis: Initial 80 mg daily, increasing gradually to 160-240 mg daily.
• Post-MI: Initial 40 mg four times daily for 2-3 days, then 80 mg twice daily. Total daily dose may be up to 240 mg.
• Essential Tremor: 40-120 mg daily.
• Hypertrophic Subaortic Stenosis: 20-40 mg three or four times daily.
• Pheochromocytoma (pre-op): 60 mg daily for 3 days prior to surgery, along with an alpha-blocker.
• Thyrotoxicosis: 10-40 mg three or four times daily.
• Anxiety: 40 mg daily, increased as needed to 40 mg three times daily.
• Proliferating Infantile Hemangioma: Initial 0.5 mg/kg twice daily, increasing as tolerated to 1.5 mg/kg twice daily.

Children:

Dosing is based on weight or age and should be determined by a physician. General guidelines:

• Arrhythmias, Thyrotoxicosis: 0.25-0.5 mg/kg three or four times daily.
• Hypertension: Initial 1-2 mg/kg daily in divided doses, up to a maximum of 4 mg/kg daily (or 640 mg).
• Migraine (under 12 years): 20 mg two or three times daily. Older children may receive adult dosages.
• Tetralogy of Fallot: 0.5 - 1mg/kg 8 hourly. Maximum 1mg/kg 6 hourly.

Pediatric Safety Considerations: Monitor heart rate, blood pressure, and blood glucose, especially in infants and young children.

Special Cases:

• Elderly Patients: Start with lower doses and titrate carefully due to potential age-related decline in organ function.
• Patients with Renal Impairment: No specific dosage adjustment is routinely recommended, but caution is advised, and lower initial doses may be considered.
• Patients with Hepatic Dysfunction: Reduce dosage due to impaired metabolism. For IV administration, consider significantly lowering the dose.
• Patients with Comorbid Conditions: Adjust dose based on the specific comorbidity, e.g., patients with diabetes may experience masked hypoglycemia symptoms.

Clinical Use Cases

• Intubation: May be used to control heart rate and blood pressure. Dosage individualized.
• Surgical Procedures: Generally, continue propranolol preoperatively but consult with the anesthesiologist. Use anesthetic agents with minimal cardiac depressant effects.
• Mechanical Ventilation: May be used as an adjunct to sedation protocols to reduce sedative requirements. 20-60 mg every 6 hours, titrated to effect.
• Intensive Care Unit (ICU) Use: Similar to mechanical ventilation, can be used to reduce sedative needs.
• Emergency Situations (e.g., supraventricular tachycardia): IV: 1-3 mg administered slowly (1 mg/minute), repeated every 2 minutes as needed up to a total of 10 mg (conscious patients) or 5 mg (patients under anesthesia). For thyrotoxic crisis: 1 mg IV over 1 minute, repeated every 2 minutes if needed.

Dosage Adjustments

Adjustments are based on individual patient response, heart rate, blood pressure, and the presence of any adverse effects. Consider renal/hepatic function, drug interactions, and comorbid conditions.

Side Effects

Common Side Effects

• Bradycardia
• Hypotension
• Dizziness
• Fatigue
• Nausea
• Diarrhea
• Bronchospasm (in susceptible individuals)
• Cold extremities

Rare but Serious Side Effects

• Heart block
• Heart failure
• Severe bronchospasm
• Hypoglycemia
• Thrombocytopenia
• Anaphylactic reactions

Long-Term Effects

• Depression
• Sexual dysfunction
• Nightmares

Adverse Drug Reactions (ADR)

• Bradycardia leading to syncope or cardiac arrest
• Severe bronchospasm requiring urgent intervention
• Angioedema

Contraindications

• Absolute: Bronchospasm/Asthma, bradycardia, second- or third-degree heart block, cardiogenic shock, severe peripheral arterial disease, untreated pheochromocytoma, sick sinus syndrome.
• Relative: Heart failure, diabetes, hepatic impairment, renal impairment.

Drug Interactions

• CYP450 Interactions: Inhibits CYP2D6. Metabolism can be affected by inducers or inhibitors of CYP1A2, 2C19, and 2D6.
• Other Interactions: Calcium channel blockers (additive bradycardia and hypotension), digoxin (additive bradycardia), insulin and oral hypoglycemics (masked hypoglycemia), nonsteroidal anti-inflammatory drugs (NSAIDs) (reduced antihypertensive effect), warfarin (increased anticoagulant effect).

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA). Use only if the potential benefit justifies the potential risk to the fetus. Propranolol crosses the placenta and can cause fetal bradycardia, hypoglycemia, and growth retardation.

• Breastfeeding: Propranolol is excreted in breast milk. Monitor infants for bradycardia and hypoglycemia. Consider alternative medications.

Drug Profile Summary

• Mechanism of Action: Non-selective beta-blocker.
• Side Effects: Bradycardia, hypotension, fatigue, dizziness, nausea. Rarely: heart block, bronchospasm, hypoglycemia.
• Contraindications: Asthma, bradycardia, heart block, cardiogenic shock.
• Drug Interactions: Calcium channel blockers, digoxin, insulin, NSAIDs, warfarin.
• Pregnancy & Breastfeeding: Use with caution; potential for fetal/neonatal bradycardia and hypoglycemia.
• Dosage: Varies by indication; see detailed dosage guidelines above.
• Monitoring Parameters: Heart rate, blood pressure, blood glucose (especially in infants and diabetics), ECG (for arrhythmias).

Popular Combinations

• Hydrochlorothiazide: Enhances the antihypertensive effect of propranolol.
• Other antihypertensive agents: Used in combination for additive blood pressure control.

Precautions

• General Precautions: Assess for allergies, cardiac, respiratory, hepatic, and renal function before starting therapy. Monitor heart rate and blood pressure. Taper off gradually to avoid rebound effects.
• Specific Populations: See “Special Cases” under Dosage.
• Lifestyle Considerations: Limit alcohol intake. Avoid smoking, as it can reduce the drug’s effectiveness. Caution when driving or operating machinery, as dizziness may occur.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Propranolol?

A: The dosage varies depending on the indication and patient factors. See the detailed dosage section above.

Q2: How should propranolol be administered?

A: Orally (tablets, capsules, solution) or intravenously in emergency situations.

Q3: Can propranolol be used in asthmatic patients?

A: No, propranolol is contraindicated in patients with asthma or bronchospasm as it can exacerbate these conditions.

Q4: What are the most common side effects of propranolol?

A: Bradycardia, hypotension, fatigue, and dizziness are the most common side effects.

Q5: Can propranolol interact with other medications?

A: Yes, propranolol can interact with various medications, including calcium channel blockers, digoxin, and insulin. Refer to the “Drug Interactions” section.

Q6: Is propranolol safe to use during pregnancy?

A: Propranolol is a Pregnancy Category C drug and should be used during pregnancy only if the potential benefits outweigh the potential risks to the fetus.

Q7: How should propranolol be discontinued?

A: Propranolol should be tapered off gradually over 1-2 weeks, especially in patients with ischemic heart disease, to avoid rebound hypertension or angina.

Q8: Can propranolol be used to treat acute anxiety attacks?

A: While propranolol can be helpful for performance anxiety or generalized anxiety, it may not be effective for acute panic attacks due to its slower onset of action. Other medications may be more appropriate.

Q9: What should I monitor in a patient taking propranolol?

A: Monitor heart rate, blood pressure, and ECG (if indicated). For infants and diabetics, blood glucose monitoring is also essential.

Q10: What is the maximum daily dose of propranolol?

A: The maximum daily dose generally should not exceed 640 mg, but this may vary depending on the formulation and indication. Always refer to the specific product information.