Diureticsvpp
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This document discusses different classes of diuretic drugs. It describes the mechanisms and sites of action of high ceiling loop diuretics like furosemide, medium efficacy thiazide diuretics, carbonic anhydrase inhibitors, potassium sparing diuretics, and osmotic diuretics like mannitol. Adverse effects and clinical uses are provided for each class. The major functions of the kidney and sites of sodium reabsorption are also reviewed.
Diureticsvpp
- 1. DIURETICS BYBY MR. V P PATILMR. V P PATIL ASST. PROF.ASST. PROF. DEPT. OF PHARMACOLOGYDEPT. OF PHARMACOLOGY BLDEA’SBLDEA’S SSM COLLEGE OF PHARMACY AND RESEARCHSSM COLLEGE OF PHARMACY AND RESEARCH CENTRE.CENTRE. VIJAYAPUR.VIJAYAPUR.
- 2. Diuretics
- 3. 1. Major Functions of The Kidney • Regulation of osmolarity of the body fluid • Regulating the volume of the extracellular fluid • Regulating concentrations of electrolytes of the extracellular fluid • Regulation of acid-base balance • Clearance of metabolic waste products (urea, uric acid, creatinine) • Production of special substances (erythropoietin, renin, prostaglandins, and thromboxane)
- 5. Diuretics are the drugs which causes net loss of Na + and water in urine by inhibiting reabsorption of Na+ & water. Normally sodium is reabsorbed --- ~ 65 % in PCT ~ 20 % in As Loop of Henle ~ 10 % in DCT ~ 5 % in CD
- 6. 65 % 10% 20 % 5 %
- 7. Diuretics High efficacy ( High ceiling diuretics): ( Inhibitors of Na+ K+2Cl Co-transport ) Sulphamoyl deri - Furosemide, Bumetanide, Phenoxy acetic acid deri - Ethacrynic acid Organomercurials - Mersalyl Medium efficacy : ( Inhibitors of Na-Cl Co-transport ) Hydrochlorothiazide, Benzthiazide, Metazolone
- 8. Diuretics Weak or adjuvant diuretics : Carbonic anhydrase inhibitors : Acetazolamide Potassium sparing diuretics : Aldosterone antagonist : Spironolactone Directly acting (Inhibitors of renal epithelial Na channel) : Triamterene , Amiloride Osmotic diuretics : Mannitol
- 9. Diuretics High ceiling loop diuretics : Furosemide (Inhibitors of Na+ K+ 2Cl Co-transport) : -- Major action on thick Ascending loop of Henle -- Diuretic response can be increased to 10 L of urine -- It is active in patients with severe renal failure
- 10. Furosemide
- 11. Diuretics Furosemide : Minor action on PCT – weak carbonic anhydrase activity – excretion of HCO3- I.V cause increase in systemic venous capacitance and decrease left ventricular filling pressure.
- 12. Diuretics Furosemide Furosemide increases calcium excretion {thiazides decrease calcium excretion} It increase the plasma uric acid levels by decreasing renal excretion – interference with tubular secretion and reabsorption. Hyperglycemia is seen with loop diuretics.
- 13. Furosemide Hypokalemia, Hearing loss, Hyperuricemia, Hyperglycemia Hypocalcemia Interactions: 1.Furosemide + ACE-I ---Antihypertensive action potentiated 2. - + NSAIDS --- Loss of diuretic effect 3. - + Aminoglycosides --- ototoxicity 4. - + Li --- Li toxicity Dose: Furosemide – 20-80mg once daily in morning Diuretics
- 14. Diuretics High ceiling loop diuretics : (Inhibitors of Na+ K+ 2Cl Co-transport) : Bumetanide : It is 40 times more potent than furosemide . Ethacrynic acid : similar to furosemide It is an irritant – orally it produces diarrhea. It is toxic and can cause hearing loss and hepatotoxicity.
- 15. Diuretics Uses of high ceiling diuretics : Edema Heart failure Acute pulmonary edema Hypertension Hypercalcemia
- 16. Diuretics Inhibitors of Na+ / Cl - symport : Hydrochlorothiazide , Metazolone, Indapamide The primary site of action is cortical diluting segment or early distal tubule. Secondary action is CA inhibition in PCT.
- 17. Diuretics Inhibitors of Na+ /Cl - symport : Thiazides : Increased urinary Na+, Cl-, K+ and Mg++ excretion Weak CAase inhibition – excretion of HCO3 Uric acid excretion, Ca++ Moderately efficacy as 90% of Na+ is reabsorbed before it reaches DCT They decrease blood pressure and increase blood sugar. They are not effective in low GFR.
- 19. Diuretics Adverse effects of thiazides diuretics : Hypokalemia Hearing loss Hyperuricemia – ppt of gout Hyperglycemia Hypercalcemia Contraindications: Hypokalemia, Ventricular arrhythmia, Volume depleted states
- 20. Diuretics Thiazides : Interactions Thiazides + Steroids, Estrogen –-- Anagonism of diuretic action - + Li --- Li toxicity - + Aminoglycosides --- Nephrotoxicity Dose: Chlorthalidone – 12.5mg-25mg, Indapamide - 20mg Uses : Edema Hypertension
- 21. Diuretics Carbonic anhydrase inhibitors : CA is an enzyme which catalyzes the reversible reaction H20 +CO2 «-------------» H2CO3. Carbonic acid ionizes into HCO3 and H+, thus helps in the transport of CO2 and H+ secretion. The CA enzyme is present in the renal tubular cells, gastric mucosa, pancreas, ciliary body and RBC.
- 23. Diuretics Carbonic anhydrase inhibitors : Acetazolamide The net effect is inhibition of HCO3 reabsorption in PCT. The secretion of H+ is inhibited. The urine produced is rich in bicarbonate -- alkaline urine – depletes body of HCO3---- producing acidosis.
- 24. Diuretics Carbonic anhydrase inhibitors : Extra – renal actions : Lowering of intraocular tension due to decreased formation of aqueous humor. Decreased gastric acid and bicarbonate secretion.
- 25. Diuretics CAase inhibitors : Acetazolamide : adverse effects : Acidosis, hypokalemia, Dose: Acetazolamide – 250mg – 1000mg/d Uses : Glaucoma To alkalinize urine In aspirin poisoning – Alkalinizes urine Acute mountain sickness(↓ collection of fluid in lungs climbers)
- 26. Diuretics Potassium Sparing Diuretics : Aldosterone antagonists – Spironolactone. Na+ channel inhibitors -- Amiloride, Triamterene.
- 28. Diuretics Potassium Sparing Diuretics : Spironolactone : Aldosterone antagonists Aldosterone acts by combining with intracellular receptors --- induces formation of proteins – which promotes reabsorption of Na+ and secretion of K+ It increases calcium excretion by direct action on the tubules Action is dependent on aldosterone
- 29. Diuretics Potassium Sparing Diuretics : Spironolactone : oral bioavailability ~75 % ↑ excretion of Na+, Cl- ↓ excretion of K+, H+, Ca++ Mg++ Converted into metabolite – canrenone
- 30. Diuretics Potassium Sparing Diuretics : Spironolactone : adverse effects Gynaecomastia, menstrual irregularities, impotence, hyperkalemia. Uses It is a weak diuretic – more useful in cirrhotic, nephrotic and refractory edema It is used to counteract the K+ loss due to thiazides and loop diuretics
- 31. Diuretics Renal epithelial Na+ channel inhibitors : Triamterene, Amiloride Non-steroidal in nature Action is similar to spironolactone – but independent of aldosterone Acts by inhibiting Na channels of the DT and CD
- 32. Diuretics Renal epithelial Na+ channel inhibitors : Triamterene, Amiloride Both are used in conjunction with thiazides and loop diuretics Hyperkalemia occurs when used with ACE inhibitors.
- 33. Diuretics Renal epithelial Na+ channel inhibitors : Amiloride : 10 times more potent than the triamterene It decreases calcium excretion and increases urate excretion Half life ~ 15 hrs Blocks entry of lithium into renal cells and mitigate DI caused by lithium
- 35. Diuretics Mannitol: Osmotic diuretics : It is a non-electrolyte – pharmacologically inert Not metabolized, freely filtered in the glomerulus, undergoes limited reabsorption Inhibits water and electrolyte reabsorption
- 36. Diuretics Mannitol: Osmotic diuretics : Expands extracellular fluid and increases GFR Increases renal blood flow - salt reabsorption is reduced Primary action is to increase urinary volume Not absorbed orally – given I.V
- 37. Diuretics Mannitol: Osmotic diuretics : Uses To maintain GFR and urine flow in renal failure Forced diuresis in poisoning To reduced IOT – by its osmotic activity
Editor's Notes
- #12: Furosemide : Pharmacokinetics : It is rapidly absorbed orally Highly bound to plasma proteins Conjugated with glucuronic acid Excreted in urine and bile