This is a very good time for some review of renal physiology. Remember that the kidney filters the extracellular fluid and the renal nephrons precisely regulate the fluid volume of the body and its electrolyte content via processes of secretion and reabsorption. Disease states such as hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis may disrupt this balance.
Diuretics are drugs that increase the rate of urine flow. Clinically useful diuretics also increase the rate of Na+ excretion (natriuresis) and of an accompanying anion, usually Cl−. Most clinical applications of diuretics are directed toward reducing extracellular fluid volume by decreasing total-body NaCl content. Diuretics play an important role in the management of cardiovascular disease and are often used in combination with other classes of drugs.
Name recognition is extremely important with these drugs. Students have missed an exam (or board) question because they didn’t recognize a drug (for example) as a potassium-sparing diuretic. This recognition is made more difficult by the fact that the names of these drugs do not have similar endings (or beginnings).
There are three main groups of diuretics and then several others—classified by their mechanisms of action and (often grouped) according to their structural class.
Inhibitors of Na+-K+-2Cl− symport: loop diuretics
Inhibitors of Na+/Cl− symport: thiazide-type diuretics
Inhibitors of renal epithelial Na+ channels: K+-sparing diuretics
Mineralocorticoid receptor antagonists (MRA): Aldosterone antagonists, K+-sparing
Inhibitors of carbonic anhydrase
Inhibitors of nonspecific cation channel: natriuretic peptides—nesiritide
Note that groups 3 and 4 are referred to as potassium-sparing. This tells you that the other groups cause a loss of potassium. You now know a major side effect of diuretics. Next consider the name loop diuretics. If you have to guess the site of action of these drugs, what would you guess? I am sure you said the loop of Henle. So you see, you already know the site of action of this group.
INHIBITORS OF THE NA+-K+-2CL− SYMPORT OR LOOP DIURETICS
The loop diuretics inhibit the symporter in the loop of Henle that moves Na+, K+, and Cl− into the cells and out of the urine.
Their action in the loop of Henle gives the loop diuretics their name. Now you simply need to remember that these drugs inhibit ion reabsorption, which increases ion concentration in the urine—taking additional water with it. Not surprisingly, this results in urinary excretion of Na+ and Cl−, but also Ca2+, Mg2+, and K+.