POTASSIUM-SPARING DIURETICS Mechanisms Potassium is normally secreted in the collecting du

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POTASSIUM-SPARING DIURETICS Mechanisms Potassium is normally secreted in the collecting ducts of the kidney, under the control of aldosterone and in proportion to the amount of sodium appearing in the lumen at this level. The aldosterone level is increased when there is a net sodium loss or a decrease in the "effective circulating blood volume." Most diuretics increase the amount of potassium excreted because they present more sodium to the collecting ducts and increase the circulating aldosterone level. The potassium-sparing agents effectively reduce sodium reabsorption in this part of the tubule and thereby reduce potassium excretion. * Aldosterone inhibition: Spironolactone is a direct aldosterone receptor antagonist in the cells of the collecting duct of the nephron and modifies protein synthesis as a result. Spironolactone also has other endocrine effects, including an antiandrogenic action. * Sodium transport inhibitors: Amiloride and triamterene block a channel necessary for sodium reabsorption in the collecting duct. Amiloride may also have an inhibitory effect on Na,K-ATPase in this part of the tubule. (PgDn key for more text) Major indications * Congestive heart failure, especially in patients with severe potassium wasting: amiloride, spironolactone, triamterene may all be used. * Primary aldosteronism and hyperaldosteronism secondary to cirrhosis or nephrotic syndrome: spironolactone is labeled for this use. * Hirsuitism (unlabeled): spironolactone (antiandrogenic action). * Lithium-induced diabetes insipidus: amiloride can block lithium absorp- tion in the collecting tubule and may correct lithium-induced diabetes insipidus. Pharmacokinetics * Spironolactone is over 90% absorbed after oral administration, is strongly protein-bound, and is excreted after extensive metabolism. It has a very slow onset of action, partially due to the lag inherent in the action of drugs that modify gene expression. It has an active me- tabolite, canrenone. * Amiloride has a low but predictable bioavailability and a much faster onset of action than spironolactone. * Triamterene has an intermediate degree of bioavailability and the shortest duration of action of the potassium-sparing diuretics. It has an active metabolite and is extensively metabolized before excretion. (PgDn key for more text) Contraindications and Warnings * All 3 drugs: hypersensitivity, hyperkalemia (above 5.5 mEq), anuria. Do not give concurrently with dietary potassium supplementation. * Warnings: do not use more than one potassium-sparing diuretic at a time. Use caution in administering amiloride to patients in metabolic or respiratory acidosis, or with renal insufficiency. * Warning: Because it is an aldosterone antagonist, spironolactone has low efficacy in patients whose aldosterone is low or normal. Patients not responding to normal dosages of the drug should not have the dose in- creased without monitoring urinary potassium excretion. Patients with low K excretion levels (less than 30 mEq/d) will usually respond to in- creased dosing. Adverse Reactions * Amiloride: - Electrolytes: hyperkalemia, acidosis. - CNS: headache, paresthesia, insomnia, depression, loss of libido. - GI: nausea, anorexia, diarrhea, vomiting. - Musculoskeletal: weakness, fatigue, muscle cramps. - Skin: rash. (PgDn key for more text) * Spironolactone: - Electrolytes: hyperkalemia, acidosis. - GI: cramping, diarrhea. - CNS: drowsiness, lethargy, ataxia. - Endocrine: gynecomastia, impotence in men; irregular menses or amenorrhea in women. * Triamterene: - Electrolytes: hyperkalemia, acidosis. - GI: diarrhea, nausea, vomiting. - Rare: interstitial nephritis; blood dyscrasias, nephrolithiasis. Toxicity and Overdosage * Electrolyte disorders (hyperkalemia): Monitor serum potassium carefully; if over 6.5 mEq/L, consider treatment with IV glucose and insulin or dialysis to reduce serum K. Dialysis is ineffective in removing spironolactone but may be of some benefit in triamterene intoxication. (PgDn key for more text) Interactions * Combination with other potassium-sparing diuretics, dietary potassium supplements, beta-blockers, or captopril lead to a high incidence of hyperkalemia. Do not combine these therapies, especially in patients with renal insufficiency. * All 3 K-sparing agents may reduce lithium clearance. * Amiloride and spironolactone may increase digoxin clearance; triamterene may increase digitalis serum levels. * Triamterene in combination with nonsteroidal anti-inflammatory drugs may result in acute renal failure. * Spironolactone may interfere with laboratory tests for digoxin levels; triamterene may interfere with the test for quinidine. (Home key to return to top of file)

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