Benzthiazide

Usage

• Benzthiazide is prescribed for the treatment of hypertension (high blood pressure) and edema (fluid retention). It’s particularly effective in edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid and estrogen therapy, and renal dysfunction. It may also be used to treat edema associated with pregnancy.

• Pharmacological Classification: Thiazide diuretic.

• Mechanism of Action: Benzthiazide inhibits sodium reabsorption in the distal convoluted tubule of the nephron, promoting excretion of sodium, chloride, and water. This leads to a decrease in blood volume and peripheral vascular resistance, thereby lowering blood pressure. It also has a direct effect on vascular smooth muscle, reducing its responsiveness to vasoconstrictors, further contributing to its antihypertensive effect.

Alternate Names

• International/Regional Variations: Benzthiazide is the common international name. There are no significant regional variations. Bendroflumethiazide is chemically and functionally similar.
• Brand Names: Exna (discontinued), Dytide (in combination with triamterene), Aquatag (discontinued)

How It Works

• Pharmacodynamics: Benzthiazide’s primary effect is diuresis, achieved by inhibiting sodium reabsorption. This lowers blood volume and indirectly reduces peripheral vascular resistance, thus lowering blood pressure.

• Pharmacokinetics:

  • Absorption: Benzthiazide is well-absorbed orally.
  • Metabolism: Limited information is available about its metabolism, likely minimal.
  • Elimination: Primarily excreted unchanged by the kidneys.

• Mode of Action: Acts on the sodium-chloride symporter in the distal convoluted tubule of the nephron, inhibiting sodium reabsorption.

• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Inhibits the sodium-chloride symporter in the distal tubule. Does not directly interact with receptors, enzymes or neurotransmitters in the conventional sense.

• Elimination Pathways: Renal excretion.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose: 25-50 mg orally twice daily after meals. Maintenance: 25-100 mg daily.
• Edema: Initial dose: 50-200 mg orally once daily or in divided doses. Maintenance: 50-150 mg daily. Maximum dose: 200 mg daily.

Children: Bendroflumethiazide: Dosage is determined by the child’s weight or age. Consult specialized resources for precise pediatric dosing.

Special Cases:

• Elderly Patients: Lower initial doses (12.5-25mg) are recommended and titration should be slower than in younger patients. Close monitoring of electrolytes is especially crucial.
• Patients with Renal Impairment: CrCl <25 mL/min: Not recommended. CrCl 25-80 mL/min: Start with 25mg twice a day and adjust cautiously up to 50-100mg/day
• Patients with Hepatic Dysfunction: Use with caution. Data on dosage adjustments is not clearly established.
• Patients with Comorbid Conditions: Caution should be exercised in patients with diabetes, gout, or electrolyte imbalances, as it can exacerbate these conditions.

Clinical Use Cases

• Benzthiazide is not typically used in situations like intubation, surgical procedures, mechanical ventilation, ICU care, or emergency settings. Its primary role is in long-term management of hypertension and edema. Other diuretics, such as furosemide, are more appropriate for acute fluid overload situations.

Dosage Adjustments

• Dose adjustments are necessary for renal impairment and should be considered in elderly patients.
• Monitor electrolytes, particularly potassium, sodium, and magnesium.

Side Effects

Common Side Effects

• Dizziness, lightheadedness
• Dehydration
• Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation)

Rare but Serious Side Effects

• Severe dehydration
• Significant electrolyte imbalances, leading to cardiac arrhythmias
• Kidney dysfunction
• Allergic reactions (skin rashes)
• Pancreatitis
• Jaundice
• Elevated Uric acid levels (potentially precipitating gout)

Long-Term Effects

• Gout
• New onset or worsening of hyperglycemia (high blood sugar)

Adverse Drug Reactions (ADR)

• Severe electrolyte disturbances
• Hypersensitivity reactions
• Renal failure

Contraindications

• Hypersensitivity to thiazide diuretics or sulfonamides.
• Anuria (absence of urine production).
• Severe kidney or liver disease.
• Pregnancy (unless benefits clearly outweigh risks).

Drug Interactions

• NSAIDs: Reduce diuretic and antihypertensive effects.
• Corticosteroids: Increase risk of hypokalemia.
• Lithium: Increased lithium levels and toxicity.
• Other antihypertensives: Additive hypotensive effects.
• Digoxin: Increased digoxin toxicity due to hypokalemia.
• Alcohol: May increase the risk of certain side effects such as dizziness, nausea, and fainting.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA). Not generally recommended during pregnancy due to potential risk of fetal or neonatal jaundice, thrombocytopenia and electrolyte abnormalities.
• Breastfeeding: Benzthiazide can suppress lactation. Not recommended during breastfeeding due to potential for transfer into breast milk and effects on the infant.

Drug Profile Summary

• Mechanism of Action: Inhibits sodium reabsorption in the distal convoluted tubule.
• Side Effects: Dizziness, dehydration, electrolyte imbalances, GI upset.
• Contraindications: Hypersensitivity, anuria, severe renal/hepatic disease.
• Drug Interactions: NSAIDs, corticosteroids, lithium, other antihypertensives.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: Adults: 25-200 mg daily, depending on indication. Pediatrics: Consult specialized references.
• Monitoring Parameters: Blood pressure, electrolytes (sodium, potassium, magnesium, calcium), uric acid, blood glucose.

Popular Combinations

• Triamterene + Benzthiazide: Potassium-sparing diuretic combination to mitigate hypokalemia.

Precautions

• Monitor electrolytes, renal function, and blood glucose regularly.
• Patients with diabetes, gout, or hepatic impairment require careful monitoring.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Benzthiazide?

A: Adults: Hypertension: 25-50mg twice a day initially, 25-100 mg for maintenance. Edema: 50-200 mg once daily or in divided doses initially, 50-150 mg for maintenance. Pediatrics: Consult specialized resources.

Q2: What are the common side effects?

A: Dizziness, lightheadedness, dehydration, electrolyte imbalances (low potassium, sodium, magnesium), and gastrointestinal issues.

Q3: Is Benzthiazide safe in pregnancy?

A: Not generally recommended. It’s Pregnancy Category C and may pose risks to the fetus.

Q4: Can Benzthiazide be used in patients with renal impairment?

A: Use with caution. It is not recommended for patients with CrCl <25ml/min. Dose adjustment is required for patients with CrCl 25-80ml/min.

Q5: What are the major drug interactions?

A: NSAIDs, corticosteroids, lithium, other antihypertensives, and digoxin.

Q6: How does Benzthiazide work to lower blood pressure?

A: It reduces blood volume by increasing sodium and water excretion, and has a direct effect on vascular smooth muscle.

Q7: What should be monitored while a patient is taking Benzthiazide?

A: Blood pressure, electrolytes (potassium, sodium, magnesium, calcium), uric acid, and blood glucose.

Q8: Can Benzthiazide be used in breastfeeding mothers?

A: Not recommended as it can suppress lactation and potentially transfer into breast milk.

Q9: What is the difference between Benzthiazide and Hydrochlorothiazide?

A: Both are thiazide diuretics, but Benzthiazide is less commonly used and data on its use is less extensive. Clinically they both act similarly. Hydrochlorothiazide is considered more potent on a mg-to-mg basis.

Q10: When should I stop Benzthiazide?

A: Never discontinue Benzthiazide abruptly without consulting a doctor. Sudden discontinuation can lead to rebound hypertension.