Diuretics

1. Diuretics

2. Diuretics are drugs which increase urine excretion mainly by decreasing reabsorption of H2O and salt from kidney tubules General clinical uses: - Congestive heart failure - Hypertension - Hepatic ascitis - Pulmonary edema

3. - Increased intracranial pressure - Nephrotic syndrome - Glaucoma Diuretics, in short, are widely used in the management of any condition associated with salt and water retention Diuretics act at different sites of the nephron (the basic unit of the kidney)

5. Diuretics categories: - Osmotic diuretics Mannitol It is a sugar, not absorbed by kidney tubules ↑ osmotic pressure in kidney tubules → withdraw H2O → ↑ urine excretion by ↓ Na+ & H2O reabsorption Site of action: Proximal convoluted tubule Major clinical use: ↑ intracranial pressure, given I.V

6. - Carbonic anhydrase inhibitors Acetazolamide Carbonic anhydrase enzyme is important enzyme responsible for reabsorption of Na+HCO3 from proximal convoluted tubules and for formation of aqueous humor (fluid of the eye) Inhibition of carbonic anhydrase enzyme increases urine outflow and decreases formation of aqueous humor

7. Acetazolamide inhibits the enzyme carbonic anhydrase → ↓ Na+HCO3 reabsorption and thus H2O → ↑ urine outflow Site of action: Proximal convoluted tubules Major clinical use: glaucoma Acetazolamide is effective orally and as an ophthalmic drops

8. - Thiazide diuretics; low efficacy diuretics Chlorothiazide; hydrochlorothiazide; indapamide; chlorthalidone... All given orally ↑ excretion of H2O, Na+, K+, Cl- and HCO3- Site of action: Ascending limb and distal convoluted tubules Diuresis is mild (↑ dose no further ↑ in diuretic effect & not so effective in pts with renal impairment) Major side effect: Hypokalemia → cardiac arrhythmias

9. - Loop, high ceiling or high efficacy diuretics Furosemide (frusemide); bumetanide, ethacrynic acid... Given orally and I.V ↑ H2O and electrolyte excretion Site of action: Ascending loop of Henle Diuresis is severe (↑ dose ↑ in diuretic effect & effective in pts with renal impairment) so small doses are required and mainly used when excessive diuresis is required e.g. severe pulmonary edema Major side effect: Hypokalemia

10. - Potassium-sparing diuretics a. Spironolactone A competitive aldosterone antagonist Site of action: Distal convoluted tubules Given orally Aldosterone → ↑ Na+reabsorption & ↑ K+ excretion, so spironolactone ↓ Na+reabsorption, ↑ H2O & ↓ K+ excretion

11. Spironolactone clinical uses: - Hyperaldosteronism, 1◦ or 2◦ ( CHF…) - Hypokalemia - Female hirsutism Spironolactone major side effect: Hyperkalemia → cardiac arrhythmias

12. b. Triamterene & amiloride K+ sparing diuretics similar to spironolactone but don’t compete with aldosterone receptors Site of action: Distal convoluted tubules and collecting ducts Given orally, ↓ Na+ reabsorption & ↓ K+ excretion Major side effect: Hyperkalemia

13. Hypokalemia due to diuretics: - Give thiazide or loop diuretics + K+ supplement e.g. KCl orally - Give thiazide or loop diuretics + K+- sparing diuretic