Potassium-sparing Diuretics A

A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia. Clinical uses include conditions of Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms 

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Patients with congenital nephrogenic diabetes insipidus are often treated with a combination of a thiazide and a potassium-sparing diuretic, without consensus on the preferred potassium-sparing diuretic. A Japanese adult was systematically studied to determine the renal effects of hydrochlorothiazide plus amiloride and hydrochlorothiazide plus triamterene (1). The combination with amiloride was superior to that with triamterene in preventing excessive urinary potassium loss, hjrpokalemia, and metabolic alkalosis. These results suggest that amiloride is the preferred add-on therapy to hydrochlorothiazide in nephrogenic diabetes insipidus. 

Potassium-sparing diuretic A diuretic that reduces the exchange of potassium for sodium in the collecting tubule a drug that increases sodium and reduces potassium excretion. Example aldosterone antagonist... 

These, then, are the major deficiencies to be filled by the design of new diuretics, and they constitute the immediate objectives of many medicinal chemists working in the area of renal drugs. The following discussion concerns some selected aspects of our own work that has been directed to the search for compounds to fill these deficiencies. This discussion will deal with three categories of compounds (1) compounds designed to mimic the mercurials, (2) the sulfonamides, particularly the hydrothiazides and (5) a heterocyclic class of potassium-sparing diuretics. A complete or detailed analysis of structure-activity relations will not be presented these either have been or will be published. Emphasis is placed on the inception of these compounds and on certain points related... 

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). 

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. 

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. 

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... 

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

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. 

Aldosterone antagonists (spironolactone, eplerenone) are also potassium-sparing diuretics but are more potent antihypertensives with a slow onset of action (up to 6 weeks with spironolactone). 

The potassium sparing diuretic, amiloride (43), also produces a Class III effect in cardiac tissue. In canine Purkinje fibres APD is increased by 35% after prolonged exposure to 5 /zM of the drug [121]. The authors suggest two potential mechanisms for this effect (1) delay of inactivation of Na+ channels, or (2) inhibition of Na+/Ca + exchange. In infarcted dogs which were subjected to a PES protocol to produce re-entrant ventricular arrhyth-... 

Amiloride is a potassium-sparing diuretic, whereas hydrochlorthiazide is a thiazide diuretic that causes loss of potassium. Enalapril is an angiotensinconverting enzyme inhibitor that retains potassium, thereby counteracting the loss of potassium caused by the thiazide diuretic. 

Spironolactone is a potassium sparing diuretic that has a different mechanism of action than other drugs of this class. 

This potassium sparing diuretic causes a moderate increase in excretion of sodium and bicarbonate ions in urine, and it raises excretion of potassium and ammonia ions. It has little effect on urine volume. 

Amyloride is also a potassium sparing diuretic that exhibits moderate activity. It is not an antagonist of aldosterone. It inhibits reabsorption of sodium ions and reduces excretion of... 

While the safe upper limit of QT is not defined, it is suggested that the interval not be permitted to exceed 0.52 seconds during treatment. If dose reduction does not eliminate the excessive prolongation, stop the drug. If concomitant diuretics are needed, consider low doses and the addition or primary use of a potassium-sparing diuretic and monitor serum potassium. 

Diuretics - Generally initiate therapy with a thiazide or other oral diuretic. Thiazide-type diuretics are drugs of choice hydrochlorothiazide or chlorthalidone are generally preferred. Reserve loop diuretics for selected patients. This therapy alone may control many cases of mild hypertension. Consider treating diuretic-induced hypokalemia (less than 3.5 mEq/L) with potassium supplementation or by adding a potassium-sparing diuretic to therapy. 

Hepatic cirrhosis-The usual initial dose is 5 or 10 mg once daily oral or IV, administered together with an aldosterone antagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, titrate the dose upward by approximately doubling until the desired diuretic response is obtained. Single doses greater than 40 mg have not been adequately studied. 

Thiazide diuretics are not effective with advanced renal insufficiency (serum creatinine level of 221 omol/l) and loop diuretics are needed, often at relatively large doses. Combining a loop diuretic with a long-acting thiazide diuretic, such as meto-lazone, is effective in patients resistant to a loop-diuretic alone. Potassium-sparing diuretics should be avoided in patients with renal insufficiency. 

The hypotensive response to captopril is accompanied by a fall in plasma aldosterone and angiotensin II levels and an increase in plasma renin activity. Serum potassium levels are not affected unless potassium supplements or potassium-sparing diuretics are used concomitantly this can result in severe hyperkalemia. 

The three principal potassium-sparing diuretic agents produce similar effects on urinary electrolyte composition. Through actions in the distal convoluted tubule and collecting duct, they cause mild natriuresis and a decrease in K" and excretion. Despite their similarities, these agents actually constitute two groups with respect to their mechanisms of action. 

B) The combination of a thiazide plus a potassium-sparing diuretic may yield an adequate diuretic response. 

Mecfianism of Action A guanidine derivative that acts as a potassium-sparing diuretic, antihypertensive, and antihypokalemicby directly interfering with sodium reabsorption in the distai tubule, TherapeuticEffect Increases sodium and water excretion and decreases potassium excretion. 

Mechanism of Action A potassium-sparing diuretic that interferes with sodium reabsorption by competitively inhibiting the action of aldosterone in the distal tubule, thus promoting sodium and water excretion and increasing potassium retention. Therapeutic Effect Produces diuresis lowers BP diagnostic aid for primary aldosteronism. 

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