Usage
- Medical Conditions: Hydrochlorothiazide + Propranolol is prescribed for the management of hypertension (high blood pressure). It is not indicated for initial therapy, but rather for patients whose blood pressure is not adequately controlled by monotherapy.
- Pharmacological Classification: This is a combination drug containing a thiazide diuretic (hydrochlorothiazide) and a beta-blocker (propranolol).
- Mechanism of Action: Hydrochlorothiazide lowers blood pressure by increasing the excretion of sodium and water from the body. Propranolol blocks beta-adrenergic receptors in the heart and blood vessels, leading to a decreased heart rate and reduced cardiac output, which in turn lowers blood pressure.
Alternate Names
- This combination is often referred to as a thiazide-beta-blocker combination.
- Brand Names: Inderide, Inderide LA (extended-release).
How It Works
- Pharmacodynamics: Hydrochlorothiazide reduces blood volume by inhibiting sodium reabsorption in the distal convoluted tubule of the nephron. Propranolol blocks beta-1 adrenergic receptors in the heart, reducing heart rate and contractility. It also blocks beta-2 receptors in the lungs and other tissues but at higher doses.
- Pharmacokinetics: Both drugs are orally absorbed. Hydrochlorothiazide is primarily excreted unchanged by the kidneys. Propranolol is extensively metabolized by the liver, primarily by CYP2D6 enzymes, with renal excretion of metabolites.
- Mode of Action: Hydrochlorothiazide acts on the sodium-chloride symporter in the distal tubule. Propranolol competitively binds to beta-adrenergic receptors.
- Elimination Pathways: Hydrochlorothiazide is primarily eliminated through renal excretion. Propranolol is metabolized in the liver and excreted in the urine, partially through CYP2D6 enzyme pathways.
Dosage
Standard Dosage
Adults:
- Initial dose: Hydrochlorothiazide 12.5-25 mg + Propranolol 40-80 mg twice daily.
- Maximum dose: Hydrochlorothiazide 50 mg + Propranolol 160 mg daily.
- Note: Doses above 160 mg of propranolol should not be given as part of the combination due to potential excessive thiazide dosage.
Children:
- Not recommended for pediatric use as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Initial dose should be at the lower end of the dosing range due to the potential for age-related decline in hepatic and renal function. Close monitoring is recommended.
- Patients with Renal Impairment: Use with caution. Dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with caution. Dose adjustments may be necessary.
- Patients with Comorbid Conditions: Individualized dosage adjustments may be required for patients with diabetes, heart failure, or other comorbidities.
Clinical Use Cases
This medication is not indicated for use in emergency or acute situations like intubation, surgical procedures, mechanical ventilation, or ICU use. It is primarily intended for chronic hypertension management in stable patients.
Dosage Adjustments
Dose adjustments may be necessary based on patient-specific factors including renal or hepatic dysfunction, metabolic disorders, other medical conditions, or concomitant medications.
Side Effects
Common Side Effects
- Dizziness, lightheadedness, fatigue, nausea, vomiting, diarrhea, constipation, upset stomach, sleep disturbances, and decreased libido.
Rare but Serious Side Effects
- Bradycardia, hypotension, bronchospasm, heart failure exacerbation, and electrolyte disturbances (hypokalemia, hyponatremia).
Long-Term Effects
- Electrolyte imbalances, metabolic abnormalities (e.g., hyperglycemia, hyperlipidemia), and impaired glucose tolerance.
Adverse Drug Reactions (ADR)
- Angioedema, Stevens-Johnson syndrome, blood dyscrasias, and severe hepatic injury.
Contraindications
- Asthma, bronchospastic disease, severe bradycardia, second- or third-degree atrioventricular block, cardiogenic shock, severe heart failure, sick sinus syndrome, anuria, hypersensitivity to sulfonamides, and hypersensitivity to propranolol.
Drug Interactions
- Other antihypertensive agents, calcium channel blockers, digoxin, insulin or other antidiabetic medications, NSAIDs, and certain antidepressants (e.g., MAOIs). There are also interactions with CYP2D6 inhibitors and inducers.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (FDA Classification). Use only if the potential benefit outweighs the potential risk to the fetus.
- Fetal risks include intrauterine growth retardation, bradycardia, hypoglycemia, and respiratory depression.
- Breastfeeding: Not recommended as both drugs are excreted in breast milk and can cause adverse effects in the neonate.
Drug Profile Summary
- Mechanism of Action: Hydrochlorothiazide: Thiazide diuretic that increases sodium and water excretion. Propranolol: Non-selective beta-blocker.
- Side Effects: Dizziness, fatigue, nausea, bradycardia, hypotension.
- Contraindications: Asthma, severe bradycardia, heart failure, anuria.
- Drug Interactions: Other antihypertensives, calcium channel blockers, digoxin.
- Pregnancy & Breastfeeding: Use with caution in pregnancy, not recommended during breastfeeding.
- Dosage: Adults: Hydrochlorothiazide 12.5-25 mg + Propranolol 40-80 mg twice daily.
- Monitoring Parameters: Blood pressure, heart rate, serum electrolytes (potassium, sodium).
Popular Combinations
Often used alone. If additional blood pressure control is needed, other antihypertensives like ACE inhibitors, ARBs or calcium channel blockers may be added.
Precautions
- Assess renal and hepatic function, electrolyte levels, and monitor for signs of heart failure exacerbation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide + Propranolol?
A: Adults: Initial dose is Hydrochlorothiazide 12.5-25 mg + Propranolol 40-80 mg twice daily. Maximum dose is Hydrochlorothiazide 50 mg + Propranolol 160 mg daily.
Q2: Can this combination be used in patients with asthma?
A: No, it is contraindicated in patients with asthma or other bronchospastic diseases.
Q3: What are the common side effects?
A: Dizziness, lightheadedness, fatigue, nausea, and bradycardia.
Q4: How should the dose be adjusted in elderly patients?
A: Start with a lower dose and titrate cautiously based on the patient’s response and renal function.
Q5: Is this combination safe during pregnancy?
A: It is Pregnancy Category C. Use only if the potential benefit justifies the potential risk to the fetus.
Q6: Can it be used in children?
A: No, its safety and efficacy haven’t been established in pediatric patients.
Q7: What should be monitored in patients taking this drug?
A: Blood pressure, heart rate, and serum electrolytes, especially potassium.
Q8: Can this combination be used in patients with diabetes?
A: Use cautiously. Monitor glucose levels closely as propranolol can mask symptoms of hypoglycemia.
Q9: What are the significant drug interactions?
A: Other antihypertensive medications, calcium channel blockers, digoxin, and NSAIDs can interact with this combination.
