Diuretics II
Download as PPTX, PDF20 likes14,585 views
This document discusses different classes of diuretics. It begins by classifying diuretics as high ceiling, medium efficacy, or weak/adjunctive. It then describes the mechanisms and uses of various weak diuretics, including carbonic anhydrase inhibitors like acetazolamide, osmotic diuretics, potassium sparing diuretics, and renal epithelial sodium channel blockers. It discusses how each works and their potential adverse effects and drug interactions. The document concludes with reviewing the key points and reminding students to prepare for the next practical class by revising topics from their book.
Diuretics II
- 1. Diuretics-II Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Lecturer, Lumbini Medical College & TH 10 April 2019 (27 Chaitra 2075), Wednesday
- 2. Answer the following… Classify diuretics Why loop diuretics are also known as high ceiling diuretics? Mechanism of action of thiazide diuretics? Which class diuretic is preferred in essential hypertension? Any two important drug interaction of diuretics.
- 3. By the end of this class, MBBS Sem III students will be able to: Explain the mechanism of action of weak diuretics Discuss the salient pharmacological aspects of weak diuretics Differentiate between the two types of potassium sparing diuretics
- 4. Diuretics: Classification High ceiling Medium efficacy Weak / adjunctive
- 5. Weak/ Adjunctive Diuretics: Classification Carbonic Anhydrase Inhibitors • Acetazolamide Osmotic Diuretics • Mannitol • Isosorbide, Glycerol Potassium sparing diuretics Renal epithelial Na+ channel blockers • Amiloride, Triamterene Aldosterone antagonists • Spironolactone, Eplerenone
- 6. Carbonic Anhydrase Inhibitors Acetazolamide, Methazolamide, Dorzolamide Reversible, non-competitive inhibitor of carbonic anhydrase Action limited by the availability of HCO3 - in luminal fluid Self limited diuretic action Na+ absorption in distal segment occurs in exchange with K+ Marked kaliuresis
- 7. CAse Inhibitors: Mechanism of Action PT cells Luminal fluid H+ Extracellular fluid NaHCO3 Na+ HCO3 - H2CO3 H2O + CO2CAse IV CAse II H2CO3 HCO3 - CAse Inhibitors
- 8. CAse inhibitors: Mechanism of Action Inhibits Carbonic anhydrase enzyme at multiple sites Type II in cells of PT • Less H+ available for exchange with Na+ Type IV on the membrane of PT cells • Less CO2 available for diffusion into cells Inhibition of Na+ and HCO3 - reabsorption in PT Na+ gets absorbed in exchange with K+ in DT, CD HCO3 - lost in excess in urine
- 9. CAse inhibitors: Mechanism of Action Inhibits Carbonic anhydrase enzyme at multiple sites Present in intercalated cells of DT and CD • Less H+ available for secretion by H+-ATPase Principal cells Intercalated cells Luminal fluid Extracellular H+ Na+ Na+ Na+ Na+ Na+ Na+
- 10. Acetazolamide: Uses Glaucoma Decrease formation of aqueous humour Mountain sickness Alters CO2 transport in lungs, tissues and brain Decreases CSF formation, lowers pH To alkalinise urine Periodic paralysis Epilepsy
- 11. Acetazolamide: Adverse effects Acidosis, hypokalaemia To be cautiously used in COPD patients Drowsiness Paraesthesia, fatigue, abdominal discomfort Hypersensitivity reaction Bone marrow depression Interferes with elimination of NH3 in urine CONTRAINDICATED in liver disease
- 12. Aldosterone antagonists Spironolactone, Eplerenone Conserve K+ indirectly, produces mild natriuresis Potassium sparing diuretics No effect in the absence of aldosterone Useful in states related to high aldosterone activity Spironolactone has hormonal side effects Eplerenone is safer in this regard
- 13. ECF Luminal Fluid Spironolactone: Mechanism of Action Aldosterone Mineralocorticoi d receptor Nucleus AIP ATP Na+ K+ K+ Spironolactone
- 14. Spironolactone: Mechanism of Action Binds to Mineralocorticoid receptors Blocks aldosterone activity • Competitive antagonist Aldosterone Induced Protein / Na+ channels not expressed Decreased absorption of Na+ and water and secretion of K+ • K+ loss in urine is decreased
- 15. Spironolactone: Uses Hypertension Adjuvant to thiazide, loop diuretics • Counteracts K+ loss • Attenuates hypertensive nephropathy Oedema Cirrhotic/ nephrotic patients Refractory Congestive Heart Failure Primary hyperaldosteronism
- 16. Spironolactone: Adverse effects Drowsiness, mental confusion, ataxia, epigastric discomfort, loose motions Interacts with progestin and androgen receptors: Gynaecomastia, erectile dysfunction, loss of libido Breast tenderness, menstrual irregularities Hyperkalaemia in renal impaired patients Acidosis in cirrhotics Peptic ulcer: CONTRAINDICATION
- 17. Eplerenone Lower affinity for androgen and progestin receptors Inactivated by CYP3A4 enzyme Indications: Moderate to severe CHF Post infarct left ventricular dysfunction Hypertension
- 18. Renal epithelial Na+ Channel inhibitors Triamterene, Amiloride Decreases K+ excretion, accompanied with small increase in Na+ loss Potassium sparing diuretics Alkaline urine produced Cl-, HCO3 - Reduces Ca2+ and Mg2+ excretion
- 19. Amiloride: Mechanism of Action ECF Luminal Fluid Principal cells of late DT and CD • Rich in K+, Low Na+ • Activity of Na+-K+ ATPase at basolateral membrane Na+ K+ K+ Amiloride Na+ Na+ K+ K+K+ K+ K+ K+ Na+ Na+
- 20. Amiloride: Mechanism of Action Blocks luminal amiloride sensitive renal epithelial Na+ channels Decrease reabsorption of Na+ in DT and CD Luminal negative charge not developed Less secretion of K+ from principal cells Less secretion of H+ from intercalated cells
- 21. Amiloride: Uses Hypertension As adjuvant • Prevents hypokalaemia • Increase natriuretic response More likely to develop hyperkalaemia if given along with ACEI/ARBs, NSAIDs, β blockers Cystic fibrosis
- 22. Adverse effects Amiloride: Nausea, diarrhoea, headache Decreases entry of lithium in CD cells • Lithium induced diabetes insipidus Triamterene: Impaired glucose tolerance, photosensitivity Rise in blood urea
- 23. Osmotic diuretics Mannitol, glycerol, isosorbide Non-electrolyte, low molecular weight Pharmacologically inert Acts by: • Raising osmolarity of plasma and tubular fluid • Gets freely filtered at glomerulus • Limits tubular water and electrolyte reabsorption (cations as well as anions)
- 24. Mannitol Tubular water and electrolyte reabsorption action of mannitol mediated by: Retaining water isosmotically in PT and Descending limb of LoH Inhibit transport process in TAL Expands extracellular fluid volume Increases renal blood flow • Corticomedullary osmotic gradient lost
- 25. Mannitol Given intravenously Uses: Increased intracranial pressure Increased intraocular pressure Counteract low osmolarity of plasma and ECF due to rapid haemodialysis or peritoneal dialysis (dialysis disequilibrium)
- 26. Mannitol CONTRAINDICATIONS: Renal insufficiency Acute tubular necrosis Anuria Pulmonary oedema Acute left ventricular failure CHF Cerebral haemorrhage • Side Effects • Headache • Nausea/ vomiting • Hypersensitiv e reactions
- 27. Post Test Inhibition of CAse by Acetazolamide is: ? Competitive and reversible ? Non-competitive and reversible ? Competitive and irreversible ? Non-competitive and irreversible
- 28. Post Test All of the following are a potassium sparing diuretics EXCEPT: ? Acetazolamide ? Triamterene ? Eplerenone ? Spironolactone
- 29. Post Test All of the following are indications of acetazolamide EXCEPT: ? Epilepsy ? Angle closure glaucoma ? High altitude pulmonary oedema ? As diuretic
- 30. Conclusion Weak diuretics either act early in PT or in late DT and CD Acetazolamide has its self limiting action, produces acidosis and marked kaliuresis Not used as diuretics Spironolactone has activity on progestin and androgen receptors Eplerenone safer in this regard Potassium sparing diuretics acts either by antagonising the activity of aldosterone or by directly inhibiting action of epithelial Na+ channels
- 31. Any queries? Next class: Today afternoon Practical class Revise the topics from BOOK Thank you.
Editor's Notes
- #12: Not used as diuretic: Self limiting action, production of acidosis and hypokalaemia