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Each segment of the nephron—proximal convoluted tubule (PCT), thick ascending limb of the loop of Henle (TAL), distal convoluted tubule (DCT), and cortical collecting tubule (CCT)—has a different mechanism for reabsorbing sodium and other ions. The subgroups of the sodium-excreting diuretics are based on these sites and processes in the nephron. Several other drugs alter water excretion predominantly. The effects of the diuretic agents are predictable from knowledge of the function of the segment of the nephron in which they act.

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Bicarbonate diureticA diuretic that selectively increases sodium bicarbonate excretion. Example: a carbonic anhydrase inhibitor
Diluting segmentA segment of the nephron that removes solute without water; the thick ascending limb and the distal convoluted tubule are active salt-absorbing segments that are not permeable by water
Hyperchloremic metabolic acidosisA shift in body electrolyte and pH balance involving elevated chloride, diminished bicarbonate concentration, and a decrease in pH in the blood. Typical result of bicarbonate diuresis
Hypokalemic metabolic alkalosisA shift in body electrolyte balance and pH involving a decrease in serum potassium and an increase in blood pH. Typical result of loop and thiazide diuretic actions
Nephrogenic diabetes insipidusLoss of urine-concentrating ability in the kidney caused by lack of responsiveness to antidiuretic hormone (ADH is normal or high)
Pituitary diabetes insipidusLoss of urine-concentrating ability in the kidney caused by lack of antidiuretic hormone (ADH is low or absent)
Potassium-sparing diureticA diuretic that reduces the exchange of potassium for sodium in the collecting tubule; a drug that increases sodium and reduces potassium excretion. Example: aldosterone antagonists
Uricosuric diureticA diuretic that increases uric acid excretion, usually by inhibiting uric acid reabsorption in the proximal tubule. Example: ethacrynic acid
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The kidney filters plasma water and solutes at the glomerulus at a very high rate (180 L/day) and must recover a significant percentage of most of these substances before excretion in the urine. The major transport mechanisms for the recovery of ions and water in the various segments of the nephron are shown in Figure 15–1. Because the mechanisms for reabsorption of salt and water differ in each of the 4 major tubular segments, the diuretics acting in these segments have differing mechanisms of action. Most diuretics act from the luminal side of the membrane. An exception is the aldosterone receptor antagonist group (eg, spironolactone and eplerenone); these drugs enter the collecting tubule cell from the basolateral side and bind to the cytoplasmic aldosterone receptor.

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Figure 15–1
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Tubule transport systems in the kidney and sites of action of diuretics. Circles with arrows denote known ion cotransporters that are targets of the diuretics indicated by the numerals. Question marks denote preliminary or incompletely documented suggestions for the location of certain drug effects. (Modified and reproduced, with permission, from Katzung ...

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