Kee: Pharmacology, 8th Edition

Chapter 43: Diuretics

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Diuretics are used for two main purposes: to decrease hypertension and to decrease
edema (peripheral and pulmonary) in heart failure (HF) and renal or liver disorders.
Diuretics produce diuresis by inhibiting sodium and water reabsorption from the kidney
tubules. Diuretics can affect one or more segments of the renal tubules.

Every 1.5 hours, the total volume of the bodys extracellular fluid (ECF) goes through the
glomeruli. Normally 99% of the filtered sodium that passes through the glomeruli is
reabsorbed. From 50% to 55% of sodium reabsorption occurs in the proximal tubules,
35% to 40% in the loop of Henle, 5% to 10% in the distal tubules, and less than 3% in the
collecting tubules.

Diuretics that act on the tubules closest to the glomeruli have the greatest effect in
causing natriuresis.

Diuretics have an antihypertensive effect because they promote sodium and water loss by
blocking sodium and chloride reabsorption. This causes a decrease in fluid volume,
lowering blood pressure. With fluid loss, edema should decrease.

Many diuretics cause the loss of other electrolytes, including potassium, magnesium,
chloride, and bicarbonate.

Thiazide, loop, and potassium-sparing diuretics are most frequently prescribed for
hypertension and for edema associated with HF.

Thiazides act on the distal convoluted renal tubule, beyond the loop of Henle, to promote
sodium, chloride, and water excretion. They are not effective for immediate diuresis and
should not be used to promote fluid loss in patients with severe renal dysfunction.
Thiazides cause a loss of sodium, potassium, and magnesium, but they promote calcium
reabsorption. Hypercalcemia may result, and the condition can be hazardous to the
patient who is digitalized or has cancer that causes hypercalcemia. Thiazides affect
glucose tolerance, so hyperglycemia can also occur.

Signs and symptoms of hypokalemia should be assessed in patients taking thiazides, and
serum potassium levels must be closely monitored. Potassium supplements are frequently
needed. Serum calcium and uric acid levels should be checked, because thiazides block
calcium and uric acid excretion.

The loop diuretics act on the thick ascending loop of Henle to inhibit chloride transport of
sodium into the circulation. Sodium and water are lost, together with potassium, calcium,
and magnesium. Loop diuretics can affect blood sugar and increase uric acid levels. The
effects of loop diuretics are dose-related. More potent than thiazides for promoting
diuresis, loop diuretics are less effective as antihypertensive agents.
Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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If furosemide alone is not effective in removing body fluid, a thiazide may be added, but
furosemide should never be combined with another loop diuretic.

Loop diuretics can increase renal blood flow up to 40%. Furosemide is a frequently
prescribed diuretic for patients whose creatinine clearance is less than 30/min and for
those with end-stage renal disease.

Furosemide and bumetanide are derivatives of sulfonamides. Ethacrynic acid, a

phenoxyacetic acid derivative, is a seldom-chosen loop diuretic. It is usually reserved for
patients who are allergic to sulfa drugs.

The most common side effects of loop diuretics are fluid and electrolyte imbalances such
as hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, and hypochloremia.

Osmotic diuretics increase the osmolality and sodium reabsorption in the proximal tubule
and loop of Henle. Sodium, chloride, potassium, and water are excreted. This group of
drugs is used to prevent kidney failure, to decrease intracranial pressure, and to decrease
intraocular pressure (IOP). The side effects and adverse reactions of mannitol, an osmotic
duretic, include fluid and electrolyte imbalance, pulmonary edema from rapid shift of
fluids, nausea, vomiting, tachycardia from rapid fluid loss, and acidosis.

Mannitol must be given with extreme caution to patients who have heart disease and HF.
It should be immediately discontinued if the patient develops HF or renal failure.

The carbonic anhydrase inhibitors block the action of the enzyme carbonic anhydrase,
which is needed to maintain the bodys acid-base balance. Inhibition of this enzyme
causes increased sodium, potassium, and bicarbonate excretion. This group of drugs is
used primarily to decrease IOP in patients with open-angle (chronic) glaucoma.

Acetazolamide, a carbonic anhydrase inhibitor, can cause fluid and electrolyte imbalance,
metabolic acidosis, nausea, vomiting, anorexia, confusion, orthostatic hypotension, and
crystalluria. Hemolytic anemia and renal calculi can also occur. These drugs are
contraindicated during the first trimester of pregnancy.

Potassium-sparing diuretics, which are weaker than thiazides and loop diuretics, are used
as mild diuretics or in combination with another diuretic.

Potassium supplements are not used when the patient takes a potassium-sparing diuretic;
in fact, serum potassium excess, called hyperkalemia, results when a potassium
supplement is taken with a potassium-sparing diuretic. The serum potassium should be
periodically monitored when the patient continuously takes a potassium-sparing diuretic.

Potassium-sparing diuretics act primarily in the collecting duct renal tubules and late
distal tubule to promote sodium and water excretion and potassium retention. The drugs
interfere with the sodium-potassium pump controlled by the mineralocorticoid hormone
aldosterone.

Spironolactone, an aldosterone antagonist, was the first potassium-sparing diuretic.

Aldosterone is a mineralocorticoid hormone that promotes sodium retention and

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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potassium excretion. Spironolactone blocks the action of aldosterone and inhibits the
sodium-potassium pump.

As a result of the action of spironolactone, the heart rate is more regular, and the
possibility of myocardial fibrosis is decreased.

The main side effect of these drugs is hyperkalemia. Caution must be used when giving
potassium-sparing diuretics to a patient with poor renal function, because the kidneys
excrete 80% to 90% of potassium.

If a potassium-sparing diuretic is given with antihypertensive ACE inhibitors,

hyperkalemia could become severe or life-threatening, because both drugs retain
potassium. Monitoring serum potassium levels is essential to safe drug therapy.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.