Hydroflumethiazide

Hydroflumethiazide is an antihypertensive agent belonging to Thiazide Diuretics.

Hydroflumethiazide is a thiazide diuretic used to treat hypertension and edema in congestive heart failure and liver cirrhosis.

Hydroflumethiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. The bioavailability of Hydroflumethiazide is about 65-75% after an oral administration. The Tmax occurs approximately 1-2.5 hours after oral administration and 40-68% of Hydroflumethiazide is protein bounded. The mean plasma half-life of Hydroflumethiazide is about 5.6 to 14.8 hours and minimally metabolized. Hydroflumethiazide is excreted in the urine; its metabolite has also been detected in the urine.

Hydroflumethiazide shows common side effects Weakness, Orthostatic hypotension, Pancreatitis, Jaundice, Nausea, vomiting, Sialadenitis, Abdominal cramping, Diarrhea/Constipation, Gastric irritation, Aplastic anemia, Agranulocytosis, Fever, Urticaria, Purpura, Muscle spasm, Vertigo/dizziness, Paresthesias, Headache, Restlessness, etc.

Hydroflumethiazide is available in the form of Oral Tablets.

Hydroflumethiazide is available in India, the US, the UK, Scotland Europe, and Ireland.

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

Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

The onset of action of Hydroflumethiazide occurs within 2 hours of its administration.

Hydroflumethiazide may remain in your body for approximately 2-3 days.

The Tmax was found within 1-2.5 hours and Cmax 10 ng/mL following the administration of Hydroflumethiazide.

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

Hydroflumethiazide is a thiazide diuretic used to treat hypertension and edema in congestive heart failure and liver cirrhosis. Hydroflumethiazide causes vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Hydroflumethiazide is an antihypertensive agent belonging to Thiazide Diuretics.

Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

Hydroflumethiazide is approved for use in the following clinical indications

• Edema

Hydroflumethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid, and estrogen therapy. Hydroflumethiazide has also been useful in edema due to various forms of renal dysfunction such as nephrotic syndrome; acute glomerulonephritis; and chronic renal failure.

• Hypertension

Hydroflumethiazide is indicated in managing hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.

• Edema

In the treatment of edema, the usual initial dose is 50 to 200 mg daily, in 1 or 2 divided doses, reduced to a dose of 25 to 50 mg on alternate days or intermittently.

• Hypertension

In the treatment of hypertension, the usual dose is 25 to 50 mg daily in 1 or 2 divided doses, either alone, or in conjunction with other antihypertensive agents. A suggested initial dose for children is 1 mg per kg of body weight daily, reduced for maintenance.

Hydroflumethiazide is available in various strengths as 12.5mg, 25mg, and 50mg.

Hydroflumethiazide is available in the form of Oral Tablets.

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

Hydroflumethiazide is contraindicated in patients with

• Documented hypersensitivity to Hydroflumethiazide or sulfonamides
• Anuria

• Fluid or electrolyte imbalance

All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance, namely, hyponatremia. hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Medication such as digitalis may also influence serum electrolytes. Warning signs, irrespective of cause, are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

• Hypokalemia

Hypokalemia may develop with thiazides as with any other potent diuretic, especially brisk diuresis. when severe cirrhosis is present, or during concomitant use of corticosteroids, including ACTH. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Digitalis therapy may exaggerate the metabolic effects of hypokalemia, especially with respect to the myocardial activity.

• Hyponatremia

Any chloride deficit is generally mild and usually does not require specific treatment, except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather. Appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

• Hyperuricemia

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

• In diabetic patients

Insulin requirements in diabetic patients may be increased, decreased, or unchanged. Latent diabetes mellitus may become manifest during thiazide administration.

• In severe renal disease

Hydroflumethiazide should be used with caution in severe renal disease. In patients with renal disease, thiazide may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

• In progressive liver disease

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

• Allergy or bronchial asthma

Sensitivity reactions may occur in patients with a history of allergy or bronchial asthma.

Consumption of alcohol is not recommended while taking Hydroflumethiazide due to the increased risk of low blood pressure.

Thiazides appear in breast milk. If the use of the drug is deemed essential, the patient may consider stopping nursing.

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes the mother and fetus to unnecessary risk. Diuretics do not prevent the development of toxemia in pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

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

• Common Adverse effects

Weakness, Orthostatic hypotension, Pancreatitis, Jaundice, Nausea/vomiting, Sialadenitis, Abdominal cramping, Diarrhea/Constipation, Gastric irritation, Aplastic anemia, Agranulocytosis, Fever, Urticaria/erythema multiforme/exfoliative dermatitis/TEN, Purpura, Muscle spasm, Vertigo/dizziness, Paresthesias, Headache, Restlessness.

• Rare Adverse effects

Hypokalemia, hyponatremia, hypercalcemia, and/or hypomagnesemia, azotemia, acute transient myopia, and acute angle-closure glaucoma, Leukopenia, Hemolytic anemia, Thrombocytopenia, Necrotizing angiitis, Pneumonitis, and pulmonary edema, Photosensitivity, Transient blurred vision, Xanthopsia, Impotence, Hyperuricemia, Hyperglycemia.

• Anticoagulants (oral): effects may be decreased when used concurrently with thiazide diuretics; dosage adjustments may be necessary.
• Antigout medications: thiazide diuretics may raise the level of blood uric acid; dosage adjustment of antigout medications may be necessary to control hyperuricemia and gout.
• Other antihypertensive medications, especially diazoxide; pre-anesthetic and anesthetic agents used in surgery; skeletal muscle relaxants, nondepolarizing, used in surgery: effects may be potentiated when used concurrently with thiazide diuretics; dosage adjustments may be necessary.
• Amphotericin B or Corticosteroids, including Corticotropin (ACTH): concurrent use with thiazide diuretics may intensify electrolyte imbalance, particularly hypokalemia.
• Cardiac glycosides: concurrent use with thiazide diuretics may enhance the possibility of digitalis toxicity associated with hypokalemia.
• Colestipol: may inhibit gastrointestinal absorption of the thiazide diuretics; administration 1 hour before or 4 hours after colestipol is recommended.
• Hypoglycemics: thiazide diuretics may raise blood glucose levels. For adult-onset diabetics, dosage adjustment of hypoglycemic medications may be necessary during and after thiazide diuretic therapy; insulin requirements may be increased, decreased, or unchanged.
• Lithium salts: concurrent use with thiazide diuretics is not recommended, as they may provoke lithium toxicity because of reduced renal clearance.
• Methenamine: effectiveness may be decreased when used concurrently with thiazide diuretics, because of alkalinization of the urine.

The common side of Hydroflumethiazide includes the following

• Common
  

Low blood pressure, Increased blood sugar levels, Increased sensitivity of the skin to sunlight, Nausea and Vomiting, Diarrhoea, Stomach cramps, Dizziness, and Fatigue.

• Rare

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

• Pregnancy

Pregnancy Category D. Teratogenic Effects

Hydroflumethiazide can cause fetal harm when administered to a pregnant woman. The hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in adults. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

• Nursing Mothers

Thiazides appear in breast milk. If the use of the drug is deemed essential, the patient may consider stopping nursing.

• Pediatric Use

Safety and effectiveness in children have not been established.

• Geriatric Use

Data not available

• Signs and Symptoms

Diuresis, lethargy progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration; GI irritation; hypermotility; transient elevation of BUN level.

• Treatment

Empty stomach by gastric lavage, taking care to avoid aspiration. Monitor serum electrolyte levels and renal function, and institute supportive measures, as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function. Treat GI effects symptomatically.

Pharmacodynamic

Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit 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

Hydroflumethiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. The bioavailability of Hydroflumethiazide is about 65-75% after an oral administration. The Tmax occurs approximately 1-2.5 hours after oral administration.

• Distribution

Approximately 40-68% of Hydroflumethiazide is protein bound. It appears to have a biphasic biological half-life with an estimated alpha phase of about 2 hours and an estimated beta-phase of about 17 hours; it has a metabolite with a longer half-life, which is extensively bound to the red blood cells.

• Metabolism and Excretion

The mean plasma half-life of Hydroflumethiazide is about 5.6 to 14.8 hours and minimally metabolized. Hydroflumethiazide is excreted in the urine; its metabolite has also been detected in the urine.

• https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6153ef9e-77f0-4233-a5bc-3e3d1f732323&type=display
• https://go.drugbank.com/drugs/DB00774
• https://www.rxlist.com/Hydroflumethiazide-drug.htm
• https://www.practo.com/medicine-info/hydroflumethiazide-5388-api
• https://www.drugs.com/ingredient/hydroflumethiazide.html