Diuretics

Pharmacology of Diuretic drugs

1. DIURETICS Dr. Ajay Kumar M. Pharm., Ph.D.

2. DIUR E TICS DEFINITION : These are dr u g s w hic h ca u s e a net los s o f Na + and water in urine There a r e s e v e r a l c ategor i e s o f di u re t i c s . All di u reti c s increases the excretion of water from body.

3. CLASSIFICATION Diuretics are Classified as: High ceiling /Loop diuretics… Thiazides. Carbonic anhydrase inhibitors. 4.Potassium –sparing diuretics. 5.Osmatic diuretics. 6.Low ceiling diuretics.

4. DIUR E TIC S C L A S SI F ICATION 1.HIGH EFFICACY DIURETICS: (Inhibitors of Na+,K+,2Cl- cotransport) Sulphamoyl deravatives: Furosemide. Bu m e tanide. Torasemide. Phenoxyacetic acid derivative: Ethacrynic acid.

5. MEDIUM EFFICACY DIURETICS 2.Medium efficacy diuretics : ( Inhibitors of Na+,Cl- symport) Benzothiadiazines(THIAZIDES): Hydrochloro thiazide. Benzthiazide. Hydroflumethe thiazide. Ciopamide. Thiazide: Chlorthalidone. Metolazone. Xipamide. Indapamide.

6. WEAK OR ADJUNCTIVE DIURETICS Weak or adjunctive diuretics: Carbonic anhydrase inhibitors: Acetazolamide Potassium –sparing diuretics : 1) Aldosterone antagonist: Spirono l acton e, Eplerenone. 2) Inhibitors of renal e pithial Na + channel : Trimterene , Amiloride. c. Osmotic diuretics: Mannitol . Isos o rbid e . Glycerol. d. Xanthines : Theophlline .

7. MECHANISM OF DIURETICS

8. MECHANIS M OF A C TION

9. MECHANISM OF ACTION OF LOOP DIURETICS

10. INDICATIONS AND SIDE EFFECTS

11. MECHANISM OF THIAZIDE DIURETICS

12. POTASSIUM- SPARING DIURETICS

13. PHAR M ACOLOGICAL ACTIONS OF DIURETICS

14. HIGH CEILING/LOOP DIURETICS High ceiling diuretics may cause a substantial decrease upto 20%of the filtered load of Nacl and water. Loop diuretics such as FUROSEMIDE inhibits the body’s ability to reabsorb sodium at the ascending loop in NEPHRON.

15. THIAZIDES Thiazide diuretics such as Hydrochlorothiazide act on the distal convoluted tubule and inhibits the sodium- chloride symporter leading to retention of water in the urine. Frequent urination is due to the increased loss of water. The long term anti –hypertensive action is based on the thiazides which decrease preload and blood pressure.

16. CARBONIC ANHYDRASE INHIBITORS Carbonic anhydrase inhibitors inhibits the enzyme carbonic anhydrase which is found in proximal convoluted tubule. This results in several effects including biocarbonate retention in the urine. Potassium retention in urine. Decreased sodium absorption. Eg: Acetazolamide. Methazolamine.

17. POTASSIUM-SPARING DIURETICS These are diu r e t i c s whic h d o not promo t e the secretion of potassium into the urine. Pota s siu m is retained and not lo s t a s mu c h a s with other diuretics. The ter m potas s i u m spa r i ng re f e r s to a n e f fects rather than a mechanism or location. Eg : Aldosterone antagonists Spironolactone

18. Which is a competitive antagonist of aldosterone. Aldosterone adds sodium channels in the cells of collecting duct and late distal tubule of the Nephron. Spirnolactone prevents aldosterone from entering the cells, and preventing sodium reabsorption. Eg: Eplerenone. Potassium canrenonate. Epithelial sodium channel blockers Eg: Amiloride. Triamterence.

19. OSMOTIC DIURETICS The c ompoun d s a s M a nnitol are filte r e d in the glomerulus, but cannot be reabsorbed. Their presence lead to an increases in the osmolarity of the filtrate. To maintain osmotic balance ,water is retained in the urine. Glucose like mannitol behave as an osmotic diuretic. Glucosuria causes a loss of hypotonic water & Na+, leading to a hypertonic state with signs of volume depletion. Such as Hypotention,Tachycardia.

20. LOW CEILING DIURETICS The lo w celin g diu r e tics are use d to indica t e an diuretic has a rapid flatting dose effect curve. It refers to a pharmacological profile , not a chemical structure.

21. USES AND SIDE EFFECTS OF DIURETICS