Diuretics are drugs that work in the kidney to increase urine flow, and thus, decrease extracellular fluid (ECF) volume. Diuretics are used to treat disorders in which for various reasons, there is an unhelpful increase in extracellular fluid volume. Two important examples are heart failure and hypertension.


The commonly used diuretics all work to block Na+ reabsorption at different sites along the nephron, as illustrated in the figure. Loop diuretics block the Na+/K+/2Cl- cotransporter that is present in the loop of Henle. Examples are furosemide and bumetanide.

The thiazide diuretics are drugs that block Na+ reabsorption in the distal tubule by blocking the Na+/Cl- cotransporter. These drugs are the diuretics that are most commonly prescribed to treat hypertension.  An example is hydrochlorothiazide.

Amiloride blocks the epithelial Na+ channel (ENaC) that is present in the cortical collecting duct. Recall that Na+ reabsorption in this segment of the nephron is regulated by the hormone aldosterone. Thus, aldosterone receptor antagonists such as spironolactone and eplerenone also work as diuretics. Amiloride and the aldosterone receptor antagonists are considered potassium-sparing diuretics.

Effects on K+

A potential adverse effect in the use of diuretics is that they can cause imbalances in the potassium (K+) in the ECF. Changes in the K+ concentration in the ECF ([K+]ECF) will affect the membrane potential of cells. Changes in the membrane potential will cause problems with electrical activity in the heart, nervous system, and muscles.

If Na+ reabsorption is blocked by either loop diuretics or thiazide diuretics, this increases Na+ delivery to the cortical collecting duct, and increases Na+ reabsorption in this segment of the nephron. Since Na+ reabsorption is coupled to K+ secretion in the cortical collecting duct, these drugs can lead to excessive K+ secretion and hypokalemia ([K+]ECF too low). Loop diuretics and thiazide diuretics may be combined with potassium sparing diuretics to counteract this possibility.

Conversely, the use of potassium-sparing diuretics could cause hyperkalemia ([K+]ECF too high). Drugs that interfere with the production or action of angiotensin II (ACE inhibitors or angiotensin II receptor blockers) also have the potential to cause hyperkalemia, because they limit the production of aldosterone. Hyperkalemia is very rare when these drugs are used alone, but it is more likely when they are used in combination (for instance combining an ACE inhibitor with an angiotensin II receptor blocker).

Quick Quiz

Fill-in Answer Correct False Correct Answer
1. Name the protein that is blocked by the loop diuretic furosemide.
2. Name the protein that is blocked by the diuretic amiloride.
3. Name the protein that is blocked by thiazide diuretics.
4. The potassium-sparing diuretic eplerenone binds to the receptor for this steroid hormone.
5. How does a thiazide diuretic affect the amount of Na+ that reaches the cortical collecting duct? [increased amount/decreased amount]
6. What is the effect on Na+ reabsorption in the cortical collecting duct? [increases/decreases]
7. How does this affect K+ secretion? [more K+ secreted/less K+ secreted]
8. Which of the following drugs could also cause hypokalemia? [amiloride; eplerenone; ACE inhibitor; furosemide]

(Spelling must be correct)