Collecting ducts, diuretic action

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. 

The answer is c. (Hardman, pp 704-706J Triamterene produces retention of the K ion by inhibiting in the collecting duct the reabsorption of Na, which is accompanied by the excretion of K ions. The loop diuretics furosemide and bumetanide cause as a possible adverse action the development of hypokalemia. In addition, thiazides (e g, hydrochlorothiazide) and the thiazide-related agents (e.g., metolazone) can cause the loss of K ions with the consequences of hypokalemia. Triamterene can be given with a loop diuretic or thiazide to prevent or correct the condition of hypokalemia. 

Hydrochlorothiazide has its proposed site of action at the distal convoluted tubule or, more specifically, at the early portion of the distal tubule. Hydrochlorothiazide inhibits the reabsorption of Na and Cl. It also promotes the reabsorption of Ca back into the blood, but inhibits the re absorption of Mg from the renal tubular fluid. The K-sparing diuretic agents (spironolactone, triamterene, and amiloride) have their site of action in the nephron at the late distal tubule and the collecting duct. These diuretic agents only cause a mild natriuretic effect... 

Anti-diuretic hormone is a small peptide shown as Figure 8.9, which is secreted by the pituitary gland located at the base of the brain. The cellular actions of ADH are mediated by activation of a G-protein linked receptor generating cAMP as second messenger. Absence of ADH or a functional defect in the action of ADH-stimulated water reabsorption in the collecting duct results in the condition diabetes insipidus, characterized by the passing of large volumes (= diabetes) of dilute (= insipidus) urine. 

Aldosterone stimulates the rates of Na+ reabsorption and K+ secretion. This is relevant to the action of spironolactone, a diuretic that is a competitive inhibitor of aldosterone (discussed later). It is also pertinent because administration of diuretics can cause secondary hyperaldosteronism, which may exaggerate the potassium wasting that is a consequence of the increased delivery of Na+ and enhanced flow through distal convoluted tubules and collecting ducts. 

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. 

In addition to their effects on distal Na+ and K+ transport, all of the K -sparing diuretics inhibit urinary H secretion by the late distal tubule and cortical collecting duct The mechanism of this inhibitory action is not totally clear. 

Mechanism of Action A potassium-sparing diuretic that inhibits sodium, potassium, ATPase. Interferes with sodium and potassium exchange in distal tubule, cortical col-lectingtubule, and collecting duct. Increases sodium and decreases potassium excretion. Also increases magnesium, decreases calcium loss. TAerapeuticEffect Produces diuresis and lowers BP. 

Figure 10.1 Sites and mechanisms of action of diuretics. The location of each cell type along the nephron is indicated by the shading patterns. Spironoiactone (not shown) is a competitive aldosterone antagonist and acts primarily in the collecting duct. PT, proximal tubule LH, loop of Henie TAL, thick ascending limb DT, distal tubule DCT, distal convoluted tubule CD, collecting duct PC, principal cell CA, carbonic anhydrase CAI, carbonic anhydrase inhibitors , primary active transport. (Adapted with permission from Ellison D H 1991 The physiologic basis of diuretic synergism its role in treating diuretic resistance. Annals of Internal Medicine 114 886-894.)...

Diuretics have many different mechanisms of action, but all of them affect transport activity or water reabsorption along the nephron and collecting duct system. Over-the-counter orally administered diuretics can contain chemically active ingredients such as pamabrom or caffeine (3,7-dihydro-l,3,7-trimethyl-lH-purine-2,6-dione C8H4QN4O2). In 1955,... 

Diuretic resistance may occur simply because excessive sodium intake overrides the ability of the diuretics to eliminate sodium. Other reasons exist for diuretic resistance in this population. Patients with ATN have a reduced number of functioning nephrons on which the diuretic may exert its action. Other clinical states like glomerulonephritis are associated with heavy proteinuria. Intraluminal loop diuretics cannot exert their effect in the loop of Henle because they are extensively bound to the protein present in the urine. Still other patients may have reduced bioavailability of oral furosemide. Possible therapeutic options to counteract each form of diuretic resistance are presented in Table 42-7. Combination therapy of loop diuretics plus a diuretic from a different pharmacologic class can be an effective tool in the setting of ARF. Loop diuretics increase the delivery of sodium chloride to the distal convoluted tubule and collecting duct. With time, these areas of the nephron compensate for the activity of the loop diuretic and increase sodium and chloride resorption. Diuretics that work at the... 

Cl carrier in the distal tubule. Einally, potassium-sparing diuretics inhibit the sodium channel in the cortical collecting duct either directly (triamterene and amiloride), or by interfering with aldosterone activity (spironolactone and eplerenone). The efficacy of a diuretic depends on the presence of several factors, including the amount of filtered solute normally reabsorbed at the site of action, the amount of solute reabsorbed distal to the site of action, and adequate delivery of drug to the site of action in the nephron. 

Spironolactone, amiloride, and triamterene are K+-sparing, weak diuretic that act at the collecting tubule and duct level. The mechanisms leading to their diuretic actions (Figure 111-6-5) and their clinical uses and adverse effects are discussed. 

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