Potassium diuretics

Drug Interactions Agents increasing serum potassium Diuretics Drugs which act on the renin-angiotensin system ... 

POTASSIUM DIURETICS-POTASSIUM-SPARING Risk of hyperkalaemia Additive effect Monitor potassium levels closely... 

The healthy kidney secretes sodium while retaining potassium. Diuretics are the more valued the less they disturb this pattern (see Section 14.1). 

The healthy kidney secretes sodium while retaining potassium. Diuretics... 

Spironolactone is the most clinically usehil steroidal aldosterone antagonist, and unlike GR antagonists, this compound is utilized much more frequendy than aldosterone agonists. Interfering with reabsorption and secretion in the late distal segment, this compound is predominantiy used with other diuretics. Canrenone, an olefinic metaboHte of spironolactone, and potassium canrenoate, in which the C-17 lactone has been hydrolyzed open, are also potent mineralocorticoid antagonists. 

Fmit and vegetable juices high in potassium have been recommended to correct hypokalemic alkalosis in patients on diuretic therapy. Apparendy the efficacy of this treatment is questionable. A possible reason for ineffectiveness is the low Ck content of most of these juices. Because Ck is high only in juices in which Na" is high, these have to be excluded (64). 

Potassium acetate is very soluble and is used in the manufacture of glass (qv), as a buffer (see Hydrogen-ION activity) or a dehydrating agent, and in medicine as a diuretic (see Diuretic agents). It is dehquescent and is used as a softening agent for papers and textiles. 

Mineralocorticoids. Aldosterone [6251-69-0] (32), the most potent natural rnineralocorticoid, also possesses a A -3-one group, an oxygen substituent at Clip, and a C17P-2-hydroxyethan-l-one side chain. In addition, the C18 of aldosterone is oxidized to an aldehyde. Mineralocorticoids, particularly aldosterone, act to retain sodium and to prevent the retention of excess potassium. Antimineral ocorticoids have been used therapeutically as diuretics and as agents that regulate blood pressure (63—65). 

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. 

Methybcanthine Diuretics. The mild diuretic effect of drinking coffee, from caffeine, and tea, mainly from theophylline, has been recogni2ed for along time. But the methylxanthines (Table 5) are of very limited efficacy when used as diuretics. The excretion of sodium and chloride ions are increased, but the potassium excretion is normal. Methylxanthines do not alter the urinary pH. Even though the methylxanthines have been demonstrated to have minor direct effects in the renal tubules, it is beUeved that they exert their diuretic effects through increased renal blood flow and GER (71). 

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. 

Triamterene (31) is a diuretic that has found acceptance because it results in enhanced sodium ion excretion without serious loss of potassium ion or significant uric acid retention. Tautomerism of aminopyrimidines (e.g., 27a and 27b) serves to make the "nonenolized" amine at the 5 position more basic than the remaining amines. Thus, condensation of 27 with benzaldehyde goes at the most basic nitrogen to form 28. Addition of hydrogen cyanide gives the a-aminonitrile (29). Treatment of that intermediate with base leads to the eyelized dihydropirazine compound (30). This undergoes spontaneous air oxidation to afford triamterene (31). ... 

Agents acting in the proximal tubule are seldom used to treat hypertension. Treatment is usually initiated with a thiazide-type diuretic. Chlorthalidone and indapamide are structurally different from thiazides but are functionally related. If renal function is severely impaired (i.e., serum creatinine above 2.5 mg/dl), a loop diuretic is needed. A potassium-sparing agent may be given with the diuretic to reduce the likelihood of hypokalemia. 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

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. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

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... 

Diuretics (see Chap. 46) may be ordered for some patients receiving a cardiotonic drug. Diuretics, as well as odier conditions or factors, such as gastrointestinal suction, diarrhea, and old age, may produce low serum potassium levels (hypokalemia). The primary care provider may order a potassium salt to be given orally or IV. 

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... 

Electrolyte imbalances that may be seen during therapy with a diuretic include hyponatremia (low blood sodium) and hypokalemia (low blood potassium), although other imbalances may also be seen. See Chapter 58 and Display 58-2 for the signs and symptoms of electrolyte imbalances. The primary care provider is notified if any signs or symptoms of an electrolyte imbalance occur. 

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