Diuretics

Diuretics

Diuretic agents are drugs that increase renal excretion of water and solute. Major purposes of diuretic therapy are to decrease fluid volume of the body, and to adjust the water and electrolyte balance. Diuretics are often used in the management of pathological conditions such as edema (e.g. in congestive heart failure and certain renal diseases) and hypertension.

Mechanism of Action

Most diuretics exert their effects by inhibiting tubular sodium and water reabsorption by epithelial cells lining the renal tubule system. Certain diuretics (such as carbonic anhydrase inhibitors, loop diuretics, thiazide-like diuretics and potassium-sparing diuretics) suppress sodium and water reabsorption by inhibiting the function of specific proteins that are responsible for (or participate in) the transportation of electrolytes across the epithelial membrane; osmotic diuretics inhibit water and sodium reabsorption by increasing intra tubular osmotic pressure. Different types of diuretics may inhibit different transporters in different segments of the tubular system.

Thiazide Diuretics

Such as hydrochlorothiazide, are moderately potent and act by inhibiting sodium and chloride reabsorption at the beginning of the distal convoluted tubule. They produce diuresis within 1-2 hours of oral administration and most have duration of action of 12-24 hours. Thiazide diuretics are used in the management of edema associated with mild to moderate congestive heart failure, renal dysfunction or hepatic disease. In hypertension, a thiazide diuretic is used at a low dose to lower blood pressure

Dosage of hydrochlorothiazide:

• Hypertension, by mouth, adult 12.5-25 mg daily; elderly initially 12.5 mg daily
• Edema, by mouth, adult initially 25 mg daily on rising, increasing to 50 mg daily

Loop Diuretics

Such as furosemide, are the most potent and rapidly produce an intense dose-dependent diuresis of relatively short duration. Oral furosemide produces diuresis within 30-60 minutes of administration, with the maximum diuretic effect in 1-2 hours. The diuretic action lasts for 4-6 hours. Intravenous furosemide produces diuresis within 5 minutes, with the maximum diuretic effect in 20-60 minutes and diuresis complete within 2 hours.

Loop diuretics inhibit reabsorption from the ascending loop of Henle in the renal tubule and are useful, particularly in situations where rapid and effective diuresis is needed such as reduction of acute pulmonary edema due to left ventricular failure. They are also used to treat edema associated with renal and hepatic disorders and are used in high doses in the management of oliguria due to chronic renal insufficiency.

Dosage of furosemide:

• Edema- adult initially 40 mg PO daily ; maintenance, 20-40 mg daily; may be increased to 80 mg daily or more in resistant edema; child 1-3 mg/kg daily (maximum 40 mg daily)
• Acute pulmonary edema, by slow intravenous injection, adult 20-50 mg, if necessary increase by 20-mg steps every 2 hours; if single dose is more than 50 mg, consider using slow intravenous infusion at a rate not exceeding 4 mg/minute; child 0.5-1.5 mg/kg daily (maximum 20 mg daily)

Potassium-Sparing Diuretics

Include amiloride and spironolactone; they are weak diuretics and reduce potassium excretion and increase sodium excretion in the distal tubule. Spironolactone, which acts by antagonizing aldosterone, has a relatively slow onset of action requiring 2-3 days to achieve maximum diuretic effect, and a similar period of 2-3 days for diuresis to cease after discontinuation of treatment. Amiloride may be used alone, but its principal use is in combination with a thiazide or a loop diuretic to conserve potassium during treatment of congestive heart failure or hepatic cirrhosis with ascites.

Spironolactone is used in the treatment of refractory edema due to heart failure, hepatic cirrhosis (with or without ascites), nephrotic syndrome and ascites associated with malignancy. It is frequently given with a thiazide or a loop diuretic, helping to conserve potassium in those at risk from hypokalemia. The most dangerous adverse effect of potassium-sparing diuretics, such as amiloride or spironolactone, is hyperkalemia, which can be life-threatening.

Osmotic Diuretics

Such as mannitol, are administered in sufficiently large doses to raise the osmolarity of plasma and renal tubular fluid. Osmotic diuretics are used to reduce or prevent cerebral edema, to reduce raised intraocular pressure. Mannitol is also used to control intraocular pressure during acute attacks of glaucoma. Reduction of cerebrospinal and intraocular fluid pressure occurs within 15 minutes of the start of infusion and lasts for 3-8 hours after the infusion has been discontinued; diuresis occurs after 1-3 hours.

Circulatory overload due to expansion of extracellular fluid is a serious adverse effect of mannitol; as a consequence, pulmonary edema can be precipitated in patients with diminished cardiac reserve, and acute water intoxication may occur in patients with inadequate urine flow.

Adverse Effects of Diuretics Hypokalemia

Hypomagnesaemia, hyponatremia, hypochloremic alkalosis, hypercalcemia; hyperglycemia; hyperuricaemia, gout; rash, photosensitivity; altered plasma lipid concentration; rarely impotence (reversible), blood disorders (including neutropenia, thrombocytopenia); pancreatitis, intrahepatic cholestasis and hypersensitivity reactions (including pneumonitis, pulmonary oedema, severe skin reactions) also reported.