Hydroflumethiazide
Mechanism :
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.
Indication :
- Used as adjuvant therapy in edema associated with hepatic cirrhosis, congestive heart failure, and corticosteroid and estrogen therapy.
- Management of hypertension either as monotherapy or in combination with other antihypertensive drugs in the more severe forms of hypertension.
Contraindications :
Not established.
Dosing :
Safety and efficacy is not established in children.
Children:
A suggested initial dose for children is 1 mg per kg of body weight daily, reduced for maintenance.
Adults:
Edema:
Initial dose is 50 to 200 mg daily, either as a single dose or 2 divided doses, reduced to a dose of 25 to 50 mg on every second day or intermittently.
Hypertension:
25 to 50 mg daily as a single dose or 2 divided doses, either as monotherapy, or in combination with other antihypertensive drugs.
Adverse Effect :
Anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, dizziness, vertigo, paresthesias, headache, xanthopsia, leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, Hypersensitivity reactions (purpura, photosensitivity, rash, urticaria, necrotizing angiitis), orthostatic hypotension, hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness.
Interaction :
Not established.
Hepatic Dose :
Caution should be observed in patients with acute or severe liver impairment as vigorous diuretic therapy may precipitate encephalopathy in susceptible patients.