Drugs acting on the renal system

Diuretics: They can be classified according to their site and mechanism of action as follows.

1. Loop diuretics (furosemide, ethacrynic acid, bumetanide and torsemide): Inhibit the Na-K-2Cl cotransporter along the thick ascending limb in the loop of Henle and macula densa. They bind at the chloride binding site of the cotransporter. Adverse effects include hypokalemic metabolic alkalosis, ototoxicity (hair cell damage), hyperuricemia, hypercalciuria, precipitation of gout and sulfa allergy (furosemide, bumetanide and torsemide).
2. Thiazides (hydrochlorothiazide, chlorthalidone and chlorothiazide) : They bind to and inhibit the NaCl transporter at the distal convoluted tubule, causing natriuresis and diuresis. They increase calcium reabsorption in the distal convoluted tubule, hence are useful in the prevention of calcium stones. Thiazides are also used in the treatment of nephrogenic diabetes insipidus. Adverse effects include hypokalemic metabolic alkalosis, hyperuricemia, precipitation of gout, hyperglycemia and hyperlipidemia.
3. Potassium sparing diuretics: They may block the apical sodium channels or ENaC (amiloride and triamterene) or act as aldosterone receptor antagonists (spironolactone and eplerenone) in the collecting ducts. Spironolactone and eplerenone are used in the treatment of hyperaldosteronism. Adverse effects include gynecomastia with spironolactone. Hyperkalemia can occur.
4. Carbonic anhydrase inhibitors (acetazolamide): It reversibly inhibits the enzyme carbonic anhydrase at the proximal tubule, resulting in reduction of hydrogen ion secretion at the renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water. Diuretic efficacy is low. They tend to cause metabolic acidosis from bicarb loss, and hypokalemia.
5. Osmotic diuretics (mannitol): It increases the tubular fluid osmolarity causing water loss or diuresis by osmosis. Adverse effects include pulmonary edema and hypernatremia.