II.Basic pharmacology of diuretic agentsCarbonic anhydraseinhibitorsThe prototypical carbonic anhydrase inhibitor is acetazolamideA、mechanisms &sites ofactionCarbonic anhydrase is present in many nephronsites, including the luminal and the epithelial cells andthered blood cells in the renal circulation.The predominant location of this enzyme is theluminal membranes of the proximal tubule cells,whereit catalyzes the dehydration of H,CO, a criticalstep inthe proximal reabsorption of bicarbonate.Inhibitors ofcarbonic anhvdrasethus block sodium bicarbonatereabsorption, causing sodium bicarbonate diuresis and areduction in total body bicarbonate stores
II. Basic pharmacology of diuretic agents Carbonic anhydrase inhibitors A、mechanisms & sites of action Carbonic anhydrase is present in many nephron sites, including the luminal and the epithelial cells and the red blood cells in the renal circulation. The predominant location of this enzyme is the luminal membranes of the proximal tubule cells, where it catalyzes the dehydration of H2CO3 a critical step in the proximal reabsorption of bicarbonate. Inhibitors of carbonic anhydrase thus block sodium bicarbonate reabsorption, causing sodium bicarbonate diuresis and a reduction in total body bicarbonate stores. The prototypical carbonic anhydrase inhibitor is acetazolamide
ProximalconvolutedInterstitiumLumen-urineABbloodtubuleNat!I NaNaNaATPK+KHCO3-1HCO3-+H+H+十HCO3H,CO3H,CO3CACA1+acetazolamidecO,+H,OH,0+CO2TheNat-H+ exchangeisrelated tocarbonic anhvdraseCarbonic anhydrase catalyzes thereaction of CO,and H,Oleadingto Hf andHCO,.Acetazolamide is a carbonic anhydraseinhibitor.The decreased ability to exchange to Na+forH+in thepresence of acetazolamide results in a mild diuresis
H2O+CO2 CO2 + H2O H2CO3 H+ + HCO3 - Proximal convoluted tubule Lumen-urine Interstitiumblood Na+ HCO3 - Na+ CA Na+ H2CO3 HCO3 - + H+ K+ K+ Na+ acetazolamide B A The Na+ -H+ exchange is related to carbonic anhydrase. Carbonic anhydrase catalyzes the reaction of CO2 and H2O leading to H+ and HCO3 - . Acetazolamide is a carbonic anhydrase inhibitor. The decreased ability to exchange to Na+ for H+ in the presence of acetazolamide results in a mild diuresis. CA ATP