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What is Loop diuretics act by: (PGI Dec 2008) and explain in detail?
Ans : B (Inhibition of Na+-K+-2 Cl-cotransport) [Ref: K.D.T. 6th/561-573)Mechanism 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 Thiazides/Thiazides 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'-Cl'Symport 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 & Eplerenone)They 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' Na+channel.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.