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Classificazione dei principali Diuretici

Classificazione dei principali Diuretici. Diuretici Osmotici Inibitori dell’Anidrasi Carbonica Tiazidici Diuretici dell’ansa Risparmiatori di potassio. Sito dell’azione dei diuretici nel nefrone. Agenti risparmiatori di potassio. Tiazidi. Diuretici dell’ansa. Tubulo prossimale.

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Classificazione dei principali Diuretici

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  1. Classificazione dei principali Diuretici • Diuretici Osmotici • Inibitori dell’Anidrasi Carbonica • Tiazidici • Diuretici dell’ansa • Risparmiatori di potassio

  2. Sito dell’azione dei diuretici nel nefrone Agenti risparmiatori di potassio Tiazidi Diuretici dell’ansa

  3. Tubulo prossimale Interstitial Space Lumen CH Na+ A K+ K+ HCO3- H+ ATP Na+ Na+ CA inhibitors H+ S H2CO3 HCO3- HCO3- CA H2CO3 TYPE IV CA TYPE II CO2+H2O CO2+H2O CH =Ion channel S A =Antiporter =Symporter

  4. Tratto Ascendente Ansa di Henle 60mV EK 70mV Membrana basolaterale K+ K+ Na+ Na+ Na+ ATPase  K+ Diuretici dell’ansa K+ 2Cl- K+ K+ Cl- Zonula occludens Cl- Ca2+ Mg2+ + ve Blood  4-10 mV - ve

  5. Diuretici dell’ansa Furosemide Etacrynic Acid Piretamide Indacrinone Brumetanide

  6. Furosemide, Piretamide, Bumetanide, Acido Etacrinico, Torasemide

  7. Interazioni Aminoglicosidi (ototossicità) Cisplatino (ototossicità) Digitalici (aritmie) Litio Sulfoniluree (iperglicemia) FANS Tiazidici (sinergismo) probenecid

  8. Tubulo distale Interstitial Space Lumen Cl- Cl- S Na+  K+ K+ S K+ K+  Cl- ATP Na+ Na+ Diuretici Tiazidici Ca2+ CH CH Cl- Cl-  Na+ Ca2+ Ex Ca2+ CH =Ion channel S A =Antiporter =Symporter

  9. Interazioni Anticoagulanti Uricosurici Sulfoniluree Insulina anestetici Digitalici Diuretici dell’ansa FANS Litio chinidina

  10. Difference between loop diuretics and Thiazides Effect Loop Diuretics Thiazides ??? ? ? ? Natriuresis ? ? ?? ? Antihypertensive ? ? ?? ? Hypokalemia ? ? Calcium Clearance ? ? Renal Blood Flow ? ? or Useful in Renal Insufficiency ++ ?

  11. Nefrone distale e diuretici risparmiatori di potassio Cellula Principale INTERSTIZIO LUME Na+ Na+ Na+  ATP K+ Amiloride Triamterene Aldosterone Spironolattone Canrenone Canrenoato di K Recettore H+ HCO3- HCO3- H+ ATP Cl- H2CO3 H+ ATP Na+ o K+ A.C. CO2+H2O Cellula intercalare A

  12. Nefrone distale e diuretici risparmiatori di potassio Cellula Principale INTERSTIZIO LUME Na+ Na+ Na+  ATP K+ Amiloride Triamterene Aldosterone Spironolattone Canrenone Canrenoato di K Recettore H+ HCO3- HCO3- H+ ATP Cl- H2CO3 H+ ATP Na+ o K+ A.C. CO2+H2O Cellula intercalare A

  13. Principali processi di biotrasformazione dello spironolattone Detioacetilazione (80% circa della dose) Canrenone Spironolattone Estere coniugato Con acido glucuronico Canreonato

  14. Interazioni farmacologiche

  15. Pharmacokinetics

  16. Adverse effects of diuretic use

  17. Factor contributing to diuretic resistance

  18. Some causes of diuretic resistance “Forward” heart failure + Excess diuresis Low cardiac input renin - + - angiotensin + Renal blood flow - aldosterone + Na+ - K+ Indo-methacin or NSAID therapy inhibits - - Probenecid and Lithium inhibit normal excretion of thiazides and loop diuretics

  19. NDI (i.e., due to lithium) is sensitive to thiazides Thiazides GFR Distal tubule Na reabsorption EC volume Proximal tubule Na & H20 reabsorption Urinary Excretion Urine Output Magaldi AJ. New insights into the paradoxical effect of thiazides in diabetes insipidus therapy. Nephrol Dial Transplant 2000 Dec;15(12):1903-5

  20. Hemodynamic consequences of diuretic therapy in patients with hypertension Blood pressure Blood pressure Fluid volume Fluid volume Peripheral Resistance Peripheral Resistance Institution of Diuretic Therapy Initial few weeks Initial few weeks

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