Question:

MOA of thiazide diuretics?

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how does thiazide diuretics increase calcium reabsorption? I thought thiazides inhibit the reabsorbing NaCl cotransporters in the early distal tubules. and if calcium reabsorption is coupled to sodium reabsorption, shouldn't calcium reabsorption also be inhibited by thiazides if they inhibit sodium reabsorption?

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  1. Thiazide diuretics are secreted into the tubular fluid by proximal tubule cells. These agents act in the distal convoluted tubule and block a Na+, Cl- symporter that is associated with the luminal membrane. This transport system moves both Na+ and Cl- into the cell using the free energy produced by the Na+, K+, ATPase. The Na+ is pumped out of the epithelial cell via this transport system in the basolateral membrane. The Cl- exits the cell via a Cl- channel. Because thiazides are related in structure to carbonic anhydrase inhibitors, some of these agents have weak carbonic anhydrase activity.

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