Diuretics

Diuretics are the drugs which increase the urine volume or increases excretion of water and sodium in urine.
The clinical used of diuretics includes relieving edema and fluid retention caused due to congestive heart failure, renal diseases and hepatic cirrhosis. Diuretics are also used in the treatment of hypertension.

The diuretics act at different sites of nephron.

Osmatic diuretics include Glycerol and Mannitol
After intravenous administration, it is filtered at the glomerulus but is not reabsorbed from the renal tubules. It osmotically attracts and retains water as it moves through the nephron and into the urine. This action reduces the tubular sodium concentration and the concentration gradient between the tubular fluid and cells and thereby retards the reabsorption of sodium. Osmatic diuretics are used for inducing diuresis, for reduction of intraocular pressure in glaucoma. mannitol is specifically used to reduces Intracerebellar pressure in cerebral edema.

The proximal tubule of nephron is site of action of carbonic anhydrase inhibitors such as acetazolamide and Dorzolamide.
Carbonic anhydrase catalyzes the reversible conversion of hydrogen ion and bicarbonate to carbon dioxide and water. Thereby enabling the reabsorption of sodium bicarbonate. This process is inhibited by carbonic anhydrase inhibitors leads to corresponding increase in its renal excretion sodium bicarbonate and water.
Carbonic anhydrase inhibitors are used in Glaucoma, Epilepsy, High-altitude sickness and they are also used to alkalinize urine in urinary tract infection and to promote excretion of certain acidic drugs.

The thick ascending limb of the loop of Henle is the site of action of High ceiling or loop diuretics like Ethacrynic acid, Furosemide, Bumetanide and Torasemide.
This segment has a high capacity for absorbing NaCl. The loop diuretics inhibit the sodium, potassium, and chloride symporter. This action produces diuresis that is much greater than that of other diuretics, this is the reason why they are called as high ceiling diuretics.
Loop diuretics are used in in treatment edema irrespective of etiology of edema cardiac, hepatic or renal. The high ceiling diuretics are preferred in congestive heart failure for rapid mobilization of edema fluid. High ceiling diuretics are used in hypertensive emergencies, when renal insufficiency is also present.

The distal tubule is site of action of thiazides such as Hydrochlorothiazide, Benzthiazide and Thiazide like diuretics such as Chlorthalidone, Metolazone, Xipamide, Indapamide.
These diuretics act mainly on the early segments of the distal tubule. Where they inhibit NaCl reabsorption by binding to the symporter responsible for the electroneutral cotransport of sodium and chloride.
Excretion of sodium, chloride and accompanying water is increased.
Thiazide and like diuretics are preferred treatment of hypertension and mild edema.

The collecting duct is site of action is potassium-sparing diuretics. In collecting duct reabsorption of sodium is coupled with potassium and hydrogen excretion.
The spironolactone reduce sodium reabsorption by antagonizing aldosterone, inhibits aldosterone-induced proteins’ (AIPs) which promote sodium reabsorption.
The other Potassium-sparing diuretics amiloride and triamterene cause of blocking of sodium channels.
The potassium-sparing diuretics are used in conjunction with other diuretic to prevent diuretic induce hypokalemia or excessive potassium excretion.