Action of diuretics at the cellular level.
Classification of diuretics is based on their site and mechanism of action in the nephron. The most frequently used substances comprise 1. the mostly proximally acting carbonic anhydrase inhibitors (CAI); 2. the loop diuretics (LD); 3. the early distally acting thiazides (TZ); and 4. the K+ sparing diuretics (KS) acting in the distal tubule. CAI such as acetazolamide inhibit the dehydration of H2CO3 at the luminal membrane, the hydration of CO2 within the proximal tubule cell and the exit of HCO-3 out of the cell. As a result of this proximal reabsorption of HCO-3 is reduced, a slight diuresis and saluresis is induced. The enhanced urinary excretion of HCO-3 will cause a metabolic acidosis. LD inhibit the Na+2Cl-K+ carrier in the thick ascending limb of the loop of Henle (TAL). This produces a marked diuresis and saluresis which is accompanied by enhanced Ca2+, Mg2+, K+ and acid excretion. TZ inhibit the Na+Cl- cotransporter in the early distal tubule. The diuresis is less marked than that induced by LD but the renal losses of K+ are comparable. KS inhibit Na+ channels present in the luminal membrane of the cortical collecting tubule. This leads to a very limited diuresis, but a marked attentuation of renal K+ losses. All diuretics act by inhibiting the admission of Na+ (LD, TZ, KS) or HCO-3 (CAI) into the cell. Their organotropy is merely due to the fact that they are concentrated in tubule fluid by volume reabsorption and by proximal tubule secretion.
Greger
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R
Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, Germany.
Lohrmann
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E
Schlatter
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E
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects; D051379:Mice; D011817:Rabbits; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects
D001639:Bicarbonates; D004232:Diuretics; D015222:Sodium Channels