Diuretic agents potassium-sparing

Polyuria and abnormal maximal concentrating ability All diuretics expect potassium/sparing agents... 

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. 

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. 

Potassium sparing diuretics differ from other diuretics in that they increase excretion of sodium ions from the body while simultaneously redueing excretion of potassium ions. In general, when used as independent agents, drags of this class are not powerful diuretics... 

Oral Severe renal impairment with oliguria or azotemia untreated Addison disease hyperkalemia from any cause adynamia episodica hereditaria acute dehydration heat cramps patients receiving potassium-sparing diuretics or aldosterone-inhibiting agents. 

Triamterene (Dyrenium) [Diuretic/Potassium-Sparing Agent]... 

Potassium-sparing diuretics, such as amiloride and triamterene. These agents reduce at the tubular level the reabsorption of sodium and water, whereas the excretion of potassium is diminished. Their primary effects are independent of aldosterone. They are slow-acting and weak diuretics, which are unsuitable as monotherapy of hypertension or heart failure. For this reason, they are always combined with thiazide or loop diuretics. Several combined preparations are commercially available. 

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. 

One of the first so-called potassium sparing, nonthiazide diuretic agents contains a pterdine nucleus. This is reflected in the use of the pterdine staring material tetra-aminopyrimidine (38-2) in the synthesis. Thus, reaction of benzaldehyde with that polyamine and potassium cyanide leads to the formation of the cyanohydrinlike a-aminonitrile (63-2) from reaction of the most basic amino group. Treatment of the intermediate with a base leads to the addition of the amine to the nitrile to give the dihydropteridine (63-3). Simple exposure to air leads to dehydrogenation and the formation of triamterine (63-4) [65]. 

Spironolactone and eplerenone bind to mineralocorticoid receptors and blunt aldosterone activity. Amiloride and triamterene do not block aldosterone, but instead directly interfere with Na+ entry through the epithelial Na+ channels (ENaC) in the apical membrane of the collecting tubule. Since K+ secretion is coupled with Na+ entry in this segment, these agents are also effective potassium-sparing diuretics. 

See Table 15-6. Potassium-sparing diuretics are most useful in states of mineralocorticoid excess or hyperaldosteronism (also called aldosteronism), due either to primary hypersecretion (Conn s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume). Use of diuretics such as thiazides or loop agents can cause or exacerbate volume contraction and may cause secondary hyperaldosteronism. In the setting of enhanced mineralocorticoid secretion and excessive delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

POTASSIUM-SPARING DIURETICS LOOP AGENTS OR THIAZIDES... 

Hypertension is a common occurrence with tacrolimus and may require treatment with antihypertensive agents. Since tacrolimus may cause hyperkalemia, potassium-sparing diuretics should be avoided... 

Amiloride is far more soluble than triamterene, and is the most widely-studied potassium-sparing diuretic. Its natriuretic effect is minimal because only 2 to 3% of the filtered sodium ion load reaches the collecting tubules of the nephron. Etozolm is a newer, long-lasting agent that has a gradual onset of action. 

The most serious side effects of diuretics are fluid depletion and electrolyte imbalance.13,88 By the very nature of their action, diuretics decrease extracellular fluid volume as well as produce sodium depletion (hyponatremia) and potassium depletion (hypokalemia). Hypokalemia is a particular problem with the thiazide and loop diuretics, but occurs less frequently when the potassium-sparing agents are used. Hypokalemia and other disturbances in fluid and electrolyte balance can produce serious metabolic and cardiac problems and may even prove fatal in some individuals. Consequently, patients must be monitored closely, and the drug dosage should be maintained at the lowest effective dose. Also, potassium supplements are used in some patients to prevent hypokalemia. 

Various thiazide, loop, or potassium-sparing diuretics can be used depending on the needs of each patient see Chapter 21, Table 21-3 for specific diuretic agents. 

Sodium removal is the next important step—by dietary salt restriction or a diuretic—especially if edema is present. In mild failure, it is reasonable to start with a thiazide diuretic, switching to more powerful agents as required. Sodium loss causes secondary loss of potassium, which is particularly hazardous if the patient is to be given digitalis. Hypokalemia can be treated with potassium supplementation or through the addition of a potassium-sparing diuretic such as spironolactone. As noted above, spironolactone should probably be considered in all patients with moderate or severe heart failure since it appears to reduce both morbidity and mortality. 

Potassium-Sparing Diuretics Loop Agents or Thiazides... 

Potassium-sparing diuretics (amiloride, spironolactone, triamterene) Additive effects with other agents increasing serum potassium concentration. May alter renal excretion of substances other than potassium (eg, digoxin, hydrogen ions). ACE inhibitors [NE] Additive hyperkalemic effect. 

POTASSIUM-SPARING DIURETICS ANTIPLATELET AGENTS-ASPIRIN 1 efficacy of spironolactone Uncertain Watch for poor response to spironolactone... 

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