Diuretics, potassium-sparing

These agents act in the distal portion of the distal tubule and the proximal part of the collecting ducts where Na is reabsorbed in exchange for K or H. Their diuretic effectiveness is relatively minor. In contrast to sulfonamide diuretics (p. 162), there is no increase in K secretion rather, there is a risk of hyperkalemia. These drugs are suitable for oral administration. 

The diuretic effect of spironolactone develops fully only with continuous administration for several days. Two possible explanations are (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone (2) an inhibition of aldosterone-stimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia (enlargement of male breast). Clinical uses include conditions of increased aldosterone secretion, e.g., liver cirrhosis with ascites. 

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Due to the enormous physicochemical heterogeneity of diuretic agents, no common characteristic fragmentation pathway has been established using EI-MS (Table 3.5). Only the sub-class of thiazides was 

TABLE 3.5 Characteristic Fragment Ions of Selected Permethylated Dinretics Using Electron Ionization 

Ethacrynic acid-methyl ester 316 phenoxyacetic acid 316 281 261 243 

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Potassium Sparing Diuretics. Triamterene and amiloride, potassium sparing diuretics, by themselves produce only slight antihypertensive effects. The main use is to prevent or to treat the hypokalemia induced by thiazide-type and high ceiling loop diuretics, such as furosemide and bumetanide. 

Potassium-Sparing Diuretics. Potassium-sparing diuretics act on the aldosterone-sensitive portion of cortical collecting tubules, and partially in the distal convoluted tubules of the nephron. The commonly used potassium-sparing diuretics are triamterene, amiloride, and spironolactone (Table 3). Spironolactone is a competitive aldosterone receptor antagonist, whereas triamterene and amiloride are not (44,45). 

Potassium-sparing by diuretic agents, particularly spironolactone, enhances the effectiveness of other diuretics because the secondary hyperaldosteronism is blocked. This class of diuretics decreases magnesium excretion, eg, amiloride can decrease renal excretion of potassium up to 80%. The most important and dangerous adverse effect of all potassium-sparing diuretics is hyperkalemia, which can be potentially fatal the incidence is about 0.5% (50). Therefore, blood potassium concentrations should be monitored carehiUy. 

Ascites. Patients with cirrhosis, especially fiver cirrhosis, very often develop ascites, ie, accumulation of fluid in the peritoneal cavity. This is the final event resulting from the hemodynamic disturbances in the systemic and splanchnic circulations that lead to sodium and water retention. When therapy with a low sodium diet fails, the dmg of choice for the treatment of ascites is furosemide, a high ceiling (loop) diuretic, or spironolactone, an aldosterone receptor antagonist/potassium-sparing diuretic. 

The first inhibitor of NHE, amiloride, was identified in 1982. This drug is a potassium-sparing diuretic that also inhibits the sodium-calcium exchanger and the conductive Na+ channel. Not all the NHE isoforms are inhibited equally by amiloride NHE1 and 2 are responsive, NHE5 is partially responsive and NHE3, 4 and 7 are resistant. Other weak and non-specific inhibitors are clonidine and cimetidine. 

No significant interactions have been reported when tiie expectorants are used as directed. The exception is iodine products. Lithium and other antithyroid drug may potentiate the hypotliyroid effects of these drug if used concurrently with iodine products. When potassium-containing medications and potassium-sparing diuretics are administered with iodine products, the patient may experience hypokalemia, cardiac arrhythmias, or cardiac arrest. Thyroid function tests may also be altered by iodine... 

The hypotensive effects of most antihypertensive dru are increased when administered with diuretics and other antihypertensives. Many dnigp can interact with the antihypertensive drugs and decrease their effectiveness (eg, antidepressants, monoamine oxidase inhibitors, antihistamines, and sympathomimetic bronchodilators). When the ACE inhibitors are administered with the NSAIDs, their antihypertensive effect may be decreased. Absorption of the ACE inhibitors may be decreased when administered with the antacids. Administration of potassium-sparing diuretics or potassium supplements concurrently with the ACE inhibitors may cause hyperkalemia. When the angiotensin II receptor agonists are administered with... 

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease tiie elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in tiie male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain. 

Additional adverse reactions of these drugs are listed in tiie Summary Drug Table Diuretics. When a potassium-sparing diuretic and a thiazide diuretic are given together, tiie adverse reactions associated with both drugp may be seen. 

Additive hypotensive effects occur when the potassium-sparing diuretics are given with alcohol, other... 

POTASSIUM-SPARING DIURETICS. Ratients taking the potassium-sparing diuretics are at risk for hyperkalemia Serum potassium levels are monitored frequently, particularly during initial treatment. 

Older adults are particularly prone to fluid volume deficit and electrolyte imbalances (see Display 46-1) while taking a diuretic. The older adult is carefully monitored for hypokalemia (when taking the loop or thiazide diuretic and hyperkalemia (with the potassium-sparing diuretics... 

The nurse must closely observe patients receiving a potassium-sparing diuretic for signs of hyperkalemia (see Display 46-1), a serious and potentially fatal electrolyte imbalance The patient is closely monitored for hypokalemia during loop or thiazide diuretic therapy. A supplemental potassium supplement may be prescribed to prevent hypokalemia. The primary health care provider may also encourage the patient to include... 

Thiazide and related diuretics, loop diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, triamterene Avoid exposure to sunlight or ultraviolet light (sunlamps, tanning beds) because exposure may cause exaggerated sunburn (photosensitivity reaction). Wear sunscreen and protective clothing until tolerance is determined. 

Consider concomitant utilization of a potassium-sparing diuretic (e.g., spironolactone, amiloride, and triamterene) if renal losses because of loop or thiazide diuretics... 

Doses should be titrated at intervals no more frequent than every 2 to 3 days. Because spironolactone is used for its antialdosterone effects, much higher doses (up to 400 mg/day) are used than those used when treating hypertension. If intolerable side effects such as gynecomastia occur with spironolactone, other potassium-sparing diuretics may be used, but clinical trials have not shown equivalent efficacy.22... 

Medications can increase the risk of hyperkalemia in patients with CKD, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, used for the treatment of proteinuria and hypertension. Potassium-sparing diuretics, used for the treatment of edema and chronic heart failure, can also exacerbate the development of hyperkalemia, and should be used with caution in patients with stage 3 CKD or higher. 

Potassium-sparing diuretics cortical collecting duct... 

Potassium-sparing diuretics act on the late portion of the distal tubule and on the cortical collecting duct. As a result of their site of action, these diuretics also have a limited effect on diuresis compared to the loop diuretics (3% of the filtered Na+ ions may be excreted). However, the clinical advantage of these drugs is that the reabsorption of K+ ions is enhanced, reducing the risk of hypokalemia. 

Potassium-sparing diuretics are often coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. In this way, edema fluid is lost to the urine while K+ ion balance is better maintained. The aldosterone antagonists are particularly useful in the treatment of primary hyperaldosteronism. 

Potassium-sparing diuretics are weak antihypertensives when used alone but provide an additive hypotensive effect when combined with thiazide or loop diuretics. Moreover, they counteract the potassium- and magnesiumlosing properties and perhaps glucose intolerance caused by other diuretics. 

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