Carbonic anhydrase inhibitors:
The majority of filtered sodium is reabsorbed in the proximal tubule through co-transport with important substances the body wants to retain. For example, when sodium exchanges with hydrogen ions, the hydrogen ions combine with bicarbonate to produce carbonic acid in the lumen. Carbonic anhydrase on the brush border breaks down carbonic acid to CO2 and water and these are reabsorbed. This process leads to complete reabsorption of bicarbonate with help from sodium (see animation of proximal tubule). Carbonic anhydrase inhibitors prevent the reabsorption of bicarbonate and lead to reduced sodium reabsorption and alkaline urine. The patient will develop metabolic acidosis due to loss of bicarbonate in the urine. Therefore, carbonic anhydrase inhibitors are only used in special clinical cases.
Loop diuretics:
Loop diuretics work by blocking the Na/K/2-CL co-transporter in the thick ascending loop of Henle (see animation ascending loop of Henle). Nomally, 25% of filtered sodium is reabsobed here. Loop diuretics are the most potent diuretics and will affect the osmotic gradient and thereby the kidneys' ability to concentrate urine. The drugs wil also inhibit absorption of calcium and magnesium in the same segment and result in hypocalcemia and hypomagnesemia. Furthermore, the secretion of uric acid will also decrease. Increased availability of sodium in the distale tubule leads to increased secretion of potassium and hypokalemia.
Thiazides:
Thiazides work in the distale tubule and block the reabsorption of sodium (see animation of distale tubule). Similar to the loop diuretics, thiazides can also lead to hypokalemia by increased availability of sodium in the distal parts of the nephron. Reabsorption of urates and calcium increase, while secretion of magnesium decreases.
Spironolactone/amiloride:
Aldosterone stimulation in the principal cells of the collecting duct leads to increased reabsorption of sodium and secretion of potassium (see animation collecting duct/aldosterone). Spironlactone is an aldosterone antagonist that blocks the aldosterone receptor in the cell, while amiloride blocks the sodium channel (ENaC) in the lumen. Both drugs lead to increased secretion of sodium and water, and reduced secretion of potassium. Therefore, they are both known as potassium-sparing diuretics, compared to the loop diuretics and thiazides that lead to loss of potassium in the urine.
Tolvaptan:
Tolvaptan is a vasopressin (ADH) antagonist that counteracts the effects of ADH in the collecting ducts. Missing expression of aquaporins on the luminal side affects the kidney's ability to concentrate urine and leads to increased secretion of water (see animation on ADH). Tolvaptan is currently exclusively used to treat hyponatremia conditions that result from SIADH (Syndrome of Inapropriate production of ADH).
Mannitol:
Mannitol is freely filtered but very little is reabsorbed. Mannitol will therefore drag with it water and electrolytes to the lumen through osmotic mechanisms and thereby work as a diuretic. It is only used in special cases.