DIURETICS

In this slide contains definition, pharmacology, classification, mechanism of action, uses, side effects of various diuretics drugs.
Presented by: MARY VISHALI BOREDDY (Department of pharmacology).
RIPER, anantapur

1. DIURETICS A Seminar as a part of curricular requirement for I year M.Pharm I Semester Presented by Ms. Mary Vishali Boreddy ( Reg.No.20L81S0104) Under the guidance/Mentorship of Mr.Sudheer Kumar.,M.Pharm Assistant professor Dept.of Pharmacology

2. DIURETICS: Also known as water pills. These are the substances used to increase the formation of urine. They excrete more water and salts. Used to treat hypertension and oedema generally. They increase formation of urine by increasing in glomerular filtration, tubular secretion and decrease in tubular reabsorption.

3. Classification:(based of efficacy) I – High ceiling diuretics / Loop diuretics : eg: a. Sulphonyl derivatives- Furosemide Torsemide Bumetanide b. Phenoxy aceticacid derivatives- Ethacrynic acid c. Organomercurials- Mesamyl II ‐ Medium efficacy diuretics : eg: a. Thiazide derivatives- Benzthiazide Hydroxy thiazide

4. b. Thiazide like derivatives- chlorthalidone Indapamide III – Weak diuretics / Low efficacy / Adjuvant diuretics : eg: a. Carbonic anhydrous inhibitors – Acetazolamide b. Potassium sparing diuretics : i- aldosterone antagonists – Spiranolactone ii – directly acting – Amioloride, Triampterene c. Osmotic diuretics – Mannitol,glycerol,Isosorbide d. Xanthines – Theophylline, caffeine

5. Pharmacology of Loop diuretics : MOA:

6. Loop diuretics acts on NKCC2 (Na + -K + -2Cl - )symporter in ascending loop of henle By competitively binding to Cl- binding site They inhibit sodium,potassium, chlorine reabsorption and thus causes their elimination in urine along with water and other ions

7. Pharmacokinetics: Oral route of administration. Bio availability- 60 percent. Low lipid solubility ,so low volume of distribution. Partially undergoes glucoronide conjugation. T ½ -3-6 hrs. Maximum drug is excreted in unchanged form.

8. USES : Hypertension Oedema like pulmonary oedema,cardiac oedema, pedal oedema. Hyper calcemia. Renal caliculi. SIDE EFFECTS : Hypokalemia. Goute. Hyponatremia. Hypocalcemia.

9. Pharmacology of Thiazides: MOA:

10. Thiazides blocks Na+-Cl- symporter in distal convoluted tubules inhibits reabsorption of sodium&chloride By lowering of Na+ concentration in distal tubules indirectly increase the activity of basolateral Na+/Ca2+ antidote increase in Ca+2 reabsorption

11. Pharmacokinetics: Rapid GI absorption. Distributed in extracellular space. Elimination unchanged in kidney. Various elimination kinetics so various half lifes ranging for hours to days.

12. USES : Hypertension. Oedema. Diabetes insipidus. SIDE EFFECTS : Hyper calcemia. Hypokalemia. Hyponatremia. Ototoxicity. Nephrotoxicity.

13. Pharmacology of Potassium sparing diuretics: A. Antagonists for aldosterone :

14. Aldosterone binds to aldosterone receptor in cytoplasm then it moves to nucleus spironolactone inhibits and causes conformational changes and produces Na+ channel for Na+ reabsorption Thus spironolactone increases sodium elimination in urine

15. PHARMACOKINETICS : Oral route of absorption. Low volume of distribution. 75 percent of spironolactone is converted into carenone(metabolite). T ½ of spironolactone-1-2 hrs. T ½ of Carenone – 18hrs. USES : Hypertension. Hypokalemia. SIDE EFFECTS : Hyperkalemia. Gynecomasteia in women and loss of sexual desire in men. Peptic ulcers.

16. B. Directly acting on renal epithelium :

17. Amiloride blocks the epithelial sodium channel(ENaC) in late distal tubules, connecting tubules and collecting duct of nephron which reduces absorption of sodium from the lumen of nephron and also reduces excretion of potassium ion into the lumen

18. PHARMACOKINETICS: Orally administered Not metabolized by liver enzymes Excreted in unchanged form T1/2- 6 hrs USES : Hypertension Oedema due to heart failure Cirrhosis of liver SIDE EFFECTS : Nausea, vomiting, decreased appetite, flatulence Unusual skin interactions, fatigue, flaccid paralysis Slow heart rate, shock

19. Pharmacology of Osmotic diuretics: MOA:

20. Osmotic diuretics prevents the normal absorption of water in proximal convoluted tubules and descending Loop of henle by enterprising a countervailing osmotic force As a result urine volume increases

21. PHARMACOKINETICS : If given oral route of administration it cause osmotic diarrhea. Mannitol is given through i/v route. T ½ -1 ½ -2 hrs. Excreted in unchanged form. USES : Chronic renal failure. Cerebral oedema. Glaucoma. SIDE EFFECTS : Diarrhea. Pulmonary oedema.

22. Pharmacology of carbonic anhydrase inhibitors: MOA:

23. Acetazolamide inhibits carbonic anhydrase enzyme in proximal tubule of kidney Inhibits the reabsorption of Na+, Cl- and bicarbonate ions Increases their excretion in urine

24. PHARMACOKINETICS : Orally administered Not metabolized by liver enzymes Excreted in unchanged form through urine T1/2 -8 hrs USES: Preoperative therapy in closed angle glaucoma and as adjuvant in open angle glaucoma Drug induced oedema, heart failure Epilepsy SIDE EFFECTS: Blood disorders, skin reactions, renal stone formation Dizziness, fatigue, headache, ataxia etc.