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increasing the proportion of the glomerular filtrate that is excreted as urine. These drugs also decrease the interstitial fluid volume (and hence, relieve edema) by a more indirect route. By lowering plasma volume, diuretic drugs increase the concentration, and thus the oncotic pressure, of the plasma within blood capillaries (chapter 14; see fig. 14.9). This promotes the osmosis of tissue fluid into the capillary blood, helping to reduce the edema.

Chapter Seventeen

The various diuretic drugs act on the renal nephron in different ways (table 17.8; fig. 17.29). On the basis of their chemical structure or aspects of their actions, commonly used diuretics are categorized as loop diuretics, thiazides, carbonic anhydrase inhibitors, osmotic diuretics, or potassium-sparing diuretics.

The most powerful diuretics, which inhibit salt and water reabsorption by as much as 25%, are the drugs that act to inhibit

Table 17.8 Actions of Different Classes of Diuretics

Category of Diuretic

Example

Mechanism of Action

Major Site of Action

Loop diuretics

Furosemide

Inhibits sodium transport

Thick segments of ascending limbs

Thiazides

Hydrochlorothiazide

Inhibits sodium transport

Last part of ascending limb and first part of distal tubule

Carbonic anhydrase

Acetazolamide

Inhibits reabsorption of bicarbonate

Proximal tubule

inhibitors

Osmotic diuretics

Mannitol

Reduces osmotic reabsorption of water

Last part of distal tubule and cortical collecting duct

by reducing osmotic gradient

Postassium-sparing

Spironolactone

Inhibits action of aldosterone

Last part of distal tubule and cortical collecting duct

diuretics

Triamterene

Inhibits Na+ reabsorption and K+ secretion

Last part of distal tubule and cortical collecting duct

Proximal convoluted tubule

Amino acids

Glucose HCO3-, PO43-

Glomerulus

Glomerulus

Increasing NaCl and urea concentrations

Distal convoluted tubule

Thiazide sensitive

NaCl

Passive

Thick ascending limb

Cortex Medulla

Descending limb

H2O/

Distal convoluted tubule

Thiazide sensitive

Thick ascending limb

Spirinolactone Action

Ascending limb

no \ADH

Ascending limb

Urea t

no \ADH

Urea t

■ Figure 17.29 Sites of action of clinical diuretics. The different diuretic drugs act on the nephron tubules at various sites to inhibit the reabsorption of water. As a result of these actions, less water is reabsorbed into the blood and more is excreted in the urine. This lowers the blood volume and pressure.

Physiology of the Kidneys active salt transport out of the ascending limb of the loop of Henle. Examples of these loop diuretics are furosemide (Lasix) and ethacrynic acid. The thiazide diuretics (e.g., hy-drochlorothiazide) inhibit salt and water reabsorption by as much as 8% through inhibition of salt transport by the first segment of the distal convoluted tubule. The carbonic anhydrase inhibitors (e.g., acetazolamide) are much weaker diuretics; they act primarily in the proximal tubule to prevent the water reabsorption that occurs when bicarbonate is reabsorbed.

When extra solutes are present in the filtrate, they increase the osmotic pressure of the filtrate and in this way decrease the reabsorption of water by osmosis. The extra solutes thus act as osmotic diuretics. Mannitol is sometimes used clinically for this purpose. Osmotic diuresis can occur in diabetes mellitus because glucose is present in the filtrate and urine; this extra solute causes the excretion of excessive amounts of water in the urine and can result in severe dehydration of a person with uncontrolled diabetes.

Complications may arise from the use of diuretics that cause an excessive loss of K+ in the urine. If K+ secretion into the tubules is significantly increased, hypokalemia (abnormally low blood K+ levels) may result. This condition can lead to neuromuscular disorders and to electrocardiographic abnormalities. People who take diuretics for the treatment of high blood pressure are usually on a low-sodium diet, and they often must supplement their meals with potassium chloride (KCl) to offset the loss of K+.

The previously mentioned diuretics can, as a result of increased Na+ delivery to the cortical collecting duct, result in the excessive secretion of K+ into the filtrate and its excessive elimination in the urine. For this reason, potassium-sparing diuretics are sometimes used. Spironolactones (Aldactone) are aldosterone antagonists that compete with aldosterone for cyto-plasmic receptor proteins in the cells of the cortical collecting duct. These drugs thus block the aldosterone stimulation of Na+ reabsorption and K+ secretion. Triamterene (Dyrenium) is a different type of potassium-sparing diuretic that appears to act on the tubule more directly to block Na+ reabsorption and K+ secretion. Combinations of spironolactone or triamterene together with hydrochlorothiazide (Aldactazide and Dyazide, respectively) are sometimes also prescribed for the diuretic treatment of hypertension.

Clinical Investigation Clue

Remember that Emily had edema and was given hydrochlorothiazide.

■ What is the action of hydrochlorothiazide, and how would this drug benefit Emily?

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