114

Practical Urology: EssEntial PrinciPlEs and PracticE

worrisome during the treatment of congestive

and ascites, tubular secretion of these agents

heart failure. In patients receiving digitalis pre-

decreases as a consequence of competition with

parations and a diuretic, diuretic-induced hypo-

accumulated toxic organic metabolites. Because

kalemia can ensue and sensitize the heart to the

thiazide and loop diuretics are lumenally act-

toxic effects of the cardiac glycoside. Measures

ing agents, decreased tubule secretion reduces

to elude the hazards of potassium deficit or to

their effectiveness. In contrast, the activity of

correct an established deficit are plentiful, but

spironolactone does not depend on filtration or

success is not guaranteed. The first steps are pre-

secretion as they gain access to their receptors

cautionary: dietary intake of large amounts of

from the blood side. Thus in patients with

potassium, avoidance of excessive NaCl intake,

cirrhosis and ascites, the effectiveness of spir-

and monitoring of serum potassium concentra-

onolactone is unimpaired. A combination of

tions. If serum potassium concentrations do not

loop diuretic in addition to spironolactone can

stabilize at an acceptable value, supplements of

be used to boost natriuresis when the diuretic

potassium chloride may be prescribed; however,

effect of spironolactone alone is inadequate.

compliance may be a problem.

Although its natriuretic action is weak, spi-

Spironolactone is most effective in patients

ronolactone lowers blood pressure in patients

with primary (adrenal adenoma or bilateral

with mild or moderate hypertension and is

adrenal hyperplasia) or secondary hyperaldos-

frequently prescribed for this purpose.

teronism (congestive heart failure, cirrhosis,

Triamterene or amiloride is generally used in

nephrotic syndrome) and is ineffective in

combination with potassium-wasting diuretics,

patients with nonfunctional adrenal glands.

especially when maintenance of normal serum

The drug prevents binding of aldosterone to a

potassium concentrations is clinically impor-

cytosolic receptor in principal cells of the col-

tant (e.g., patients with dysrhythmias, receiving

lecting tubule. Consequently, the hormonal

a cardiac glycoside, or with low serum potas-

stimulus to formation of aldosterone-induced

sium concentrations). Fixed-combination prep-

proteins ceases. In the absence or reduction in

arations are generally not appropriate for initial

the amount of this protein, the permeability of

therapy but may be more expedient when the

the luminal membrane to sodium and potas-

dosage schedule is demonstrated to be correct.

sium decreases, with the result that sodium

Because these drugs possess a different site and

excretion is enhanced and potassium secretion

mechanism of action from those of thiazides or

is diminished. Cellular entry of potassium

loop agents, they are sometimes administered

across the basolateral membrane also abates.

together to increase the response in patients

Because spironolactone diminishes the lumen

who are refractory to a single agent.

negative potential in the collecting tubule, pro-

ton secretion decreases. Spironolactone is used

for correction of hypokalemia. The drug is also

Suggested Reading

administered alone, with thiazides, or a loop

diuretic, to reduce the ECF volume without

Brenner B, ed. The Kidney. 8th ed. Philadelphia, PA: W.B.

causing potassium depletion or hypokalemia.

The drug is especially appropriate for the treat-

Saunders Co; 2007

Giebisch G,Seldin D,eds.Diuretic Agents: Clinical Physiology

ment of cirrhosis with ascites, a condition

and Pharmacology. San Diego, CA: Academic Press;

invariably associated with secondary hyperal-

1997

dosteronism. In comparison to loop or thiazide

Koeppen BM, Stanton BA, eds. Renal Physiology. 2nd ed. St.

diuretics, spironolactone is equivalent or more

Louis, MO: Mosby Year Book; 1996

effective. The reason for this observation could

Rose BD, Post TW. Clinical Physiology of Acid-Base and

be related to the differences in the mechanism

Electrolyte Disorders. New York, NY: Mc Graw Hill, Inc.;

of drug action. Thiazides and loop are highly

2001. ISBN 5

Valtin H, Schafe JA, eds. Renal Function. 3rd ed. Boston, MA:

protein bound and enter the tubule fluid pri-

Little, Brown & Company; 1995

marily by proximal tubule secretion and not by

Vander AJ et al., eds. Renal Physiology. 5th ed. New York, NY:

glomerular filtration. In patients with cirrhosis

McGraw-Hill, Inc.; 1995