<prompt> Loop diuretics act by: PGI Dec 2008Inhibition of Na-Cl- SymportInhibition of Na-K-2 Cl- cotransportInhibition of Na-K ATPaseInhibition of H-K ATPase  <response>: Ans : B Inhibition of Na-K-2 Cl-cotransport Ref: K.D.T. 6th561-573Mechanism of Action of DiureticsHigh Efficacy or High Ceiling or Loop DiureticsThere act by inhibition of Na-K-2 Cl- cotransport Major site of action is the thick ascending loop of henie ASCLH i.e. site II. Recently distinct absorptive or secretory isoforms of Na- K-2C1- cotransporter have been isolated. Absorptive isoform is exclusively expressed at the luminal membrane of thick AscLH while secretory form is expressed on the basolateral membrane of most glandular epithelial cells.Medium Efficacy or ThiazidesThiazides Like DiureticsThese act by inhibition of Na-CI- symportPrimary site of action is in cortical diluting segment or the early DT site III. Here they inhibit Na-ClSymport at the luminal membrane.Acetazoiamide It is a sulfonamide derivative which non competitively but reversibly inhibits carbonic anhydrase in proximal tubule cells resulting in slowing of hydration of CO2 - decreased availability of H to exchange with luminal Na through the Na-H antiporter.The net effect is inhibition of HCO3 accompanying Na reabsorption in PT - prompt but mild alkaline diuresis is ensues.Aldosterone Antagonist Spironolactone EplerenoneThey acts from the interstitial side of the tubular cell, combine with the mineralocorticoid receptor inh ibits the formation of aldosterone induced proteins. AlPs promote Na reabsorption by a no. of mechanism K secretion.Amiloride TriamtereneThe luminal membrane of late DT CD cells express a distinct amiloride sensitive or renal epithelial Nachannel.Amiloride Triamtereen block the luminal Na channels- indirectly inhibit K excretion, while the net excess loss of Na is minor most of it has already been reabsorbed.Osmotic Diuretics Mannitol. Glycerol Isosorbide Mannitol is a non electrolyte of low M.W. that is pharmacologically inert.Mannitol appear to limit tubular water electrolyte reabsorption.Though the primary action of mannitol is to increase urinary volume, excretion of all cations anions is also enhanced. 