O-BENDRO TABLET (Each tablet contains Bendroflumethiazide 5mg)

Indications

• Hypertension
• Oedema in heart failure
• Nephrogenic diabetes insipidus
• Partial pituitary diabetes insipidus
• Management of chronic hypoglycaemia

Dosage

Children: For children aged 1 month to 1 year: 50–100 micrograms/kg daily; for children aged 1 to 11 years: Initially 50–400 micrograms/kg daily; for children aged 12–17 years: Initially 5–10 mg once daily.

Adults: Initially 2.5 mg once daily, adjusted according to response; maximum 10 mg per day.

Mechanism of action

Bendroflumethiazide works by inhibiting sodium reabsorption at the distal convoluted tubule in the kidneys, leading to increased excretion of sodium and water, which decreases blood volume and blood pressure.

Pharmacodynamics

As a thiazide diuretic, Bendroflumethiazide causes a dose-dependent diuresis and reduction in blood pressure. It also has effects on electrolyte balance, particularly reducing potassium levels and increasing calcium reabsorption.

Pharmacokinetics

Bendroflumethiazide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours after oral administration. It has a half-life of approximately 6-15 hours, and is primarily excreted in urine. Its effects can last for 24 hours or more.

Contra-indications

• Bilateral renovascular disease
• Severe or symptomatic aortic stenosis
• History of idiopathic or hereditary angioedema

Adverse effects

• Agranulocytosis
• Cholestasis
• Hypotension
• Angioedema
• Alopecia
• Blood disorders

Interactions

• Thiazide diuretics may interact with ACE inhibitors
• Increased risk of agranulocytosis in collagen vascular disease

Precautions

• Use with care in patients with hypertrophic cardiomyopathy
• Use with care in patients with a history of angioedema

Pregnancy

Use only if the benefits outweigh the risks; refer to specific guidelines.

Breast-feeding

The amount present in milk is too small to be harmful; large doses may suppress lactation.

Storage

Store below 25°C. Protect from light.

Formulations

• Bendroflumethiazide 2.5 mg tablets
• Oral suspension
• Oral solution

Mechanism of action

As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. ...BENZOTHIADIAZIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE...INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/ NATURE OF CHEM INTERACTION BETWEEN THIAZIDES & SPECIFIC RENAL RECEPTORS RESPONSIBLE FOR CHLORURETIC EFFECT IS NOT KNOWN; NO CRITICAL ENZYMATIC REACTIONS HAVE BEEN IDENTIFIED. /THIAZIDE DIURETICS/ ...MAY DECR EXCRETION OF URIC ACID IN MAN, THUS INCR ITS CONCN IN PLASMA. HYPERURICEMIC EFFECT RESULTS PRIMARILY FROM INHIBITION OF TUBULAR SECRETION OF URATE. ... UNLIKE MOST OTHER NATRIURETIC AGENTS...DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM... /ENHANCE/ EXCRETION OF MAGNESIUM... /THIAZIDE DIURETICS/ THIAZIDES INHIBIT REABSORPTION OF SODIUM &...CHLORIDE IN DISTAL SEGMENT. ... AS CLASS...HAVE IMPORTANT ACTION ON EXCRETION OF POTASSIUM THAT RESULTS FROM INCR SECRETION OF CATION BY DISTAL TUBULE. ... GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES, PARTICULARLY WITH IV ADMIN FOR EXPTL PURPOSES. /THIAZIDE DIURETICS/ For more Mechanism of Action (Complete) data for BENDROFLUMETHIAZIDE (11 total), please visit the HSDB record page.

Pharmacodynamics

Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits Na⁺/Cl^- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.