Bendroflumethiazide

Bendroflumethiazide is an antihypertensive agent belonging to Thiazide Diuretics.

Bendroflumethiazide is a thiazide diuretic used to treat hypertension and edema in people with congestive heart failure, or a kidney disorder such as nephrotic syndrome

Bendroflumethiazide completely absorbed from the GI tract. Time to peak plasma concentration of Bendroflumethiazide was found to be approximately 3-6 hours. It is highly bound to plasma protein albumin, about 96%. It undergoes a fairly extensive metabolism. Plasma half-life was found to be approximately 3-4 hours. As an unchanged drug, it is excreted via urine about 30%.

Bendroflumethiazide shows common side effects Hypotension, Hyperglycaemia, Vomiting, Nausea, Diarrhoea, Stomach cramps, Dizziness, Fatigue, etc.

Bendroflumethiazide is available in the form of Oral Tablets.

Bendroflumethiazide is available in India, China, US, England, UK and Hong Kong

Bendroflumethiazide belonging to the Thiazide Diuretics, acts as an antihypertensive agent.

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.

The onset of action of Bendroflumethiazide occurs within 2 hours.

The Duration of Action for Bendroflumethiazide in the body is approximately 12-18 hours.

The Tmax was found within 3-4 hours following the oral administration of Bendroflumethiazide.

Bendroflumethiazide comes as an Oral Tablet taken by mouth. It is usually taken once daily or on alternate days.

Bendroflumethiazide is a thiazide diuretic used to treat hypertension and edema in people with congestive heart failure or a kidney disorder such as nephrotic syndrome. It should be used with caution in patients with severe kidney disease.

Bendroflumethiazide is an antihypertensive agent belonging to Thiazide Diuretics.

Inhibits sodium, chloride, and water reabsorption in the renal distal tubules, thereby producing diuresis with a resultant reduction in plasma volume; hypothetically may reduce peripheral resistance through increased prostacyclin synthesis.

Bendroflumethiazide is approved for use in the following clinical indications.

• Edema

Bendroflumethiazide is indicated in the treatment of oedema associated with conditions such as congestive heart failure, nephrotic syndrome, and cirrhosis of the liver.

• Hypertension

Bendroflumethiazide is indicated in the treatment of essential hypertension where it may be used as the sole antihypertensive agent or as an adjunct to other medicines whose action it potentiates.

• Edema

Adult: Initially: 5-10 mg in the morning, daily or on alternate days.

Maintenance dose: 2.5-5 mg orally once a day. Max: 20 mg daily.

Child:

1 month to 2-year: 50-100 mcg/kg/day

>2-12-year: 50-400 mcg/kg/day (max of 10 mg), followed by 50-100 mcg/kg/day, adjusted according to response.

• Hypertension

Adult: 2.5 mg in the morning daily, either alone or in conjunction with other antihypertensive. Max: 20 mg daily.

Child:

1 month to 2-year: 50-100 mcg/kg/day

>2-12 years: 50-400 mcg/kg/day (max of 10 mg), followed by 50-100 mcg/kg/day, adjusted according to response.

Bendroflumethiazide is available in various strengths as 5mg and 10mg.

Bendroflumethiazide is available in the form of Oral Tablets.

Avoid consumption of a high-salt or high-sodium diet while taking Bendroflumethiazide.

Bendroflumethiazide is contraindicated in patients with

• Hypersensitivity to this or other sulfonamide-derived drugs.
• Anuria
• Renal decompensation
• Pregnancy

• Mild to moderate Renal and Hepatic Dysfunctions

Thiazide diuretics should be used with caution in patients with mild or moderate renal or hepatic dysfunction. Renal function should be monitored during bendroflumethiazide therapy. Thiazides can cause electrolyte imbalance which is more severe in patients with hepatic and renal impairment and in those receiving higher or prolonged doses.

• Hypokalemia

Elderly patients and those on intensive or long-term treatment need regular blood tests to monitor serum electrolytes (especially potassium). Hypokalemia should be corrected by adding potassium supplements to the regimen and may be required in the following cases:

If the patient is vomiting, has diarrhea or is suffering from an acute febrile or chronic

illness (especially cirrhosis of the liver or heart failure).

To prevent hypokalemia, possible arrhythmias and other ECG changes in patients

receiving digitalis especially if diuretic treatment is prolonged.

In patients at risk of myocardial infarction.

In patients admitted for cardiac surgery.

In patients receiving concurrent therapy with carbenoxolone or corticosteroids.

• Hypomagnesaemia

In cirrhosis of the liver, thiazides may precipitate hepatic encephalopathy. The risk of hypomagnesaemia is increased in alcoholic cirrhosis.

• Hypercalcemia

Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

• Patients with Diabetes mellitus

Diabetes mellitus may be aggravated by Bendroflumethiazide and cause symptoms in patients with latent disease. Bendroflumethiazide may impair control of diabetes in patients receiving sulphonyl urea’s.

• Patients with porphyria

Caution is required when treating patients with porphyria.

• Hyperlipidemia

Thiazides may cause or aggravate hyperlipidemia.

Consumption of alcohol is not recommended when on treatment with Bendroflumethiazide due to the increased risk of low blood pressure.

Bendroflumethiazide suppresses lactation and, although the amounts passing into breast milk are small, it should be avoided in breast feeding mothers.

Thiazide diuretics readily cross the human placenta, with umbilical cord blood thiazide levels approximately equivalent to maternal plasma thiazide levels. Bendroflumethiazide should only be given during pregnancy when there are no alternatives and benefits outweigh risk.

Avoid consumption of a high-salt or high-sodium diet while taking Bendroflumethiazide.

• Common Adverse effects

Orthostatic hypotension, Hyponatremia, Hypokalemia, Anorexia, Upset stomach, Diarrhea.

• Rare Adverse effects

Drowsiness, Nausea, Vomiting, hyperuricemia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia, hepatitis, hepatic function, impairment, paresthesia, polyuria, uremia, allergic reactions.

• Allopurinol: Bendroflumethiazide may antagonize the action of allopurinol by causing retention of urate in the kidney. Caution is advised when using this combination.
• Anion exchange resins: Colestyramine and colestipol reduce absorption of Bendroflumethiazide. This can be prevented by leaving an interval of two hours between doses of Bendroflumethiazide and the anion exchange resin.
• Antiarrhythmics: The cardiotoxicity of disopyramide, amiodarone, flecainide and quinidine is increased if hypokalaemia occurs following the administration of Bendroflumethiazide. The actions of lidocaine and mexiletine are antagonised by hypokalaemia.
• Antidepressants: There is an increased risk of postural hypotension if Bendroflumethiazide is given with tricyclic antidepressants. There may also be a risk of hypokalaemia if thiazides are given with reboxetine. Concomitant use with MAOIs may result in an enhanced hypotensive effect.
• Antidiabetics: Bendroflumethiazide antagonises the hypoglycaemic effects of sulfonylureas, with a potential loss of diabetic control.
• Antiepileptics: There is an increased risk of hyponatraemia when Bendroflumethiazide and carbamazepine are taken concurrently.
• Antifungals: The risk of hypokalaemia is increased when amphotericin and Bendroflumethiazide are taken concurrently.
• Antihypertensives: Bendroflumethiazide may enhance the antihypertensive effect of ACE inhibitors and angiotensin-II antagonists. There is an increased risk of first dose hypotension if prazosin is given to a patient taking Bendroflumethiazide.
• Antipsychotics: Hypokalaemia increases the risk of ventricular arrhythmias with pimozide or thioridazine so concomitant use should be avoided.
• Calcium salts: Bendroflumethiazide reduces urinary excretion of calcium so there is an increased risk of hypercalcaemia when calcium salts are taken concurrently. Serum calcium levels should be monitored to ensure that they do not become excessive.
• Calcium channel blockers and peripheral vasodilators: The hypotensive effect of calcium channel blockers and moxisylyte may be enhanced when co-administered with Bendroflumethiazide.
• Corticosteroids: Corticosteroids may exacerbate hypokalaemia associated with Bendroflumethiazide and its diuretic activity may be antagonized.
• Cytotoxics: Concomitant use with cisplatin can lead to an increased risk of nephrotoxicity and ototoxicity.
• Digoxin: The hypokalaemic effect of Bendroflumethiazide may enhance sensitivity to digoxin when taken concurrently. Patients should be monitored for signs of digoxin intoxication, especially arrhythmias. The dose of digoxin should be reduced and potassium supplements given, so that digoxin toxicity will not develop.
• Hormone antagonists: There is an increased risk of hyponatraemia when Bendroflumethiazide is used concomitantly with aminoglutethamide. Bendroflumethiazide can cause an increased risk of hypercalcaemia when co-administered with toremifene.
• Lithium: Bendroflumethiazide inhibits the tubular elimination of lithium, resulting in an elevated plasma lithium concentration and risk of toxicity. Plasma lithium concentrations must be monitored when these drugs are given concurrently.
• Muscle relaxants: The hypotensive activity of Bendroflumethiazide may be increased by baclofen and tizanidine. Bendroflumethiazide may enhance the neuromuscular blocking activity of non-depolarising muscle relaxants, such as tubocurarine, gallamine, alcuronium and pancuronium.
• NSAIDs: Bendroflumethiazide may enhance the nephrotoxicity of NSAIDs. Indomethacin and ketorolac antagonize the diuretic effect of Bendroflumethiazide, this occurs to a lesser extent with ibuprofen, piroxicam and naproxen. The effects of concurrent use should be monitored and the dose of Bendroflumethiazide modified if necessary.
• Estrogens and progestogens: Estrogens and combined oral contraceptives antagonize the diuretic effect of Bendroflumethiazide.
• Sympathomimetics: Sympathomimetics can cause hypokalaemia. The risk of serious heart arrhythmias in asthmatic patients may be increased if Bendroflumethiazide is added to their medication.
• Theophylline: Concomitant administration of theophylline and Bendroflumethiazide increases the risk of hypokalaemia.
• Ulcer healing drugs: There is an increased risk of hypokalaemia and a decrease in diuretic activity when carbenoxolone and Bendroflumethiazide are taken together. Patients should be monitored and given potassium supplements when required.
• Vitamins: The risk of hypercalcaemia is increased if Bendroflumethiazide is given with vitamin D.

The common side of Bendroflumethiazide include the following

• Common
  

Hypotension, Hyperglycaemia, Vomiting, Nausea, Diarrhoea, Stomach cramps, Dizziness, Fatigue.

• Rare

Fever, Haemolytic anaemia, Necrotizing angiitis, Pneumonitis and pulmonary edema, Photosensitivity, Weight gain, Redness of eye, sexual problems, Pancreatitis, Jaundice, Nausea/vomiting, Thrombocytopenia, Sialadenitis, Aplastic anaemia, Agranulocytosis, Leukopenia.

• Pregnancy

Pregnancy Category C

Bendroflumethiazide is best avoided for the management of edema of pregnancy or hypertension in pregnancy as it crosses the placenta and its use may be associated with hypokalaemia, increased blood viscosity and reduced placental perfusion. There is inadequate evidence of safety in human pregnancy. There are rare reports of foetal and neonatal bone marrow depression, thrombocytopenia, electrolyte imbalance, hypoglycaemia and jaundice. Expectant mothers who receive thiazide diuretics may be at increased risk from acute haemorrhagic pancreatitis. In parturition, thiazides may cause uterine inertia and delay the onset of labour. Thiazides are only indicated in pregnancy if edema complicates a pathological lesion and, even then, after assessing risk versus benefit including the undesirability of administering medicines in the first trimester.

• Nursing Mothers

Bendroflumethiazide suppresses lactation and, although the amounts passing into breast milk are small, it should be avoided in breast feeding mothers.

• Symptoms

Nausea, vomiting, diarrhoea, dehydration, dizziness, weakness, muscle cramps, diuresis, increased frequency of micturition with polyuria and thirst. Extreme cases may show depletion of intravascular volume, hypotension and peripheral circulatory failure. CNS depression (eg. drowsiness, lethargy and coma) may occur without cardiovascular or respiratory depression. Hypokalaemia and mild hypoglycaemia are likely to be present if diuresis is profound.

• Treatment

Activated charcoal may help reduce absorption of substantial amounts if given within one hour of ingestion. Treatment should be symptomatic and directed at fluid and electrolyte replacement which should be monitored together with the blood pressure and renal function. Hyponatraemia should be treated with water deprivation rather than the administration of sodium chloride. Cathartics should be avoided.

Pharmacodynamic

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.

Pharmacokinetics

• Absorption

Bendroflumethiazide completely absorbed from the GI tract. Time to peak plasma concentration of Bendroflumethiazide found to be approximately 3-6 hour.

• Distribution

Bendroflumethiazide is highly bound to plasma protein albumin about 96%.

• Metabolism and Excretion
  

Bendroflumethiazide undergoes fairly extensive metabolism. Plasma half-life found to be approximately 3-4 hours. As unchanged drug it is excreted via urine about 30%.

• https://www.drugs.com/dosage/bendroflumethiazide.html
• https://go.drugbank.com/drugs/DB00436
• https://www.mims.com/philippines/drug/info/bendroflumethiazide?mtype=generic
• https://www.medsafe.govt.nz/profs/datasheet/a/arrow-bendrofluazidetab.pdf