Natriuretic effect

Urodilantin, a 32-amino acid natriuretic peptide synthesized by the kidney and found in urine but not in plasma, is beheved to compHcate the interpretation of the natriuretic effects of ANP (58). There have been reports of natriuretic peptides related to ANP that have been isolated from several sources, including the brain, eg, brain natriuretic peptide (BNP) [114471-18-0] (59—61). 

The answer is b. (Katzung, pp 256-258J Amiloride is a K-sparing diuretic with a mild diuretic and natriuretic effect The parent compound is active, and the drug is excreted unchanged in the urine. Amiloride has a 24-hour duration of action and is usually administered with a thiazide or loop diuretic (e.g., furosemide) to prevent hypokalemia. The site of its... 

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... 

Foop diuretics (furosemide, bumetanide, torsemide) are usually necessary to restore and maintain euvolemia in HF. In addition to acting in the thick ascending limb of the loop of Henle, they induce a prostaglandin-mediated increase in renal blood flow that contributes to their natriuretic effect. 

The aldosterone antagonist, spironolactone> has been successfully used for the treatment of hypertension. Its natriuretic effect is associated with potassium retention. Specificity of spironolactone in certain types of hypertension had been suggested, but subsequently denied in well controlled studies(15,16). 

It is now becoming apparent that a single daily dose (rather than 2-3 doses per day) significantly enhances patient compliance and, therefore, effectiveness of treatment. For this reason, the long-acting diuretics which can be administered once a day offer an important advantage chlorthalidone, metolazone, trichlor-methiazide can be administered once a day with a 24 hour natriuretic effect. 

In vitro studies suggest that the GRK4 SNPs impair the function of receptors, increase blood pressure, and impair the diuretic and natriuretic effects of dopamine Dj-like agonist stimulation. Inappropriate desensitization of the dopamine D, receptor in renal proximal tubules in hypertension may result in the decreased ability of the kidney to eliminate a sodium chloride load—a key risk factor in the development of hypertension. 

Tolerance associated with renal retention of fluid does not occur an initial natriuretic effect is often observed, especially with the nifedipine group of blockers. 

Spironolactone is poorly absorbed after oral administration and has a delayed onset of action it may take several days until a peak effect is produced. It has a somewhat slower onset of action than triamterene and amiloride (discussed later), but its natriuretic effect is modestly more pronounced, especially during long-term therapy. Spironolactone is rapidly and extensively metabolized, largely to the active metabohte canrenone. Canrenone and potassium canrenoate, its K+ salt, are available for clinical use in some countries outside the United States. Canrenone has a half-life of approximately 10 to 35 hours. The metabolites of spironolactone are excreted in both the urine and feces. New selective aldosterone receptor antagonists (SARA), such as eplerenone, have been developed but have not yet been introduced into clinical practice. Eplerenone and canrenone exhibit fewer steroidlike side effects (gynecomastia, hirsutism). 

Potassium-sparing diuretics are useful both to avoid excessive potassium depletion and to enhance the natriuretic effects of other diuretics. Aldosterone receptor antagonists in particular also have a favorable effect on cardiac function in people with heart failure. 

Theoretically, PGE2 and PGF2K should be superior to oxytocin for inducing labor in women with preeclampsia-eclampsia or cardiac and renal diseases because, unlike oxytocin, they have no antidiuretic effect. In addition, PGE2 has natriuretic effects. However, the clinical benefits of these effects have not been documented. In cases of intrauterine fetal death, the prostaglandins alone or with oxytocin seem to cause delivery effectively. 

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. 

Aspirin has been shown to slightly reduce the natriuretic effect of spironolactone in healthy individuals, possibly by reducing active renal tubular secretion of canrenone, the active metabolite of spironolactone. However, the hypotensive effect of spironolactone and its effect on urinary potassium excretion in hypertensive patients is apparently not affected. Until more clinical data are available on this potential interaction, patients receiving both drugs should be monitored for signs and symptoms of decreased clinical response to spironolactone [65]. 

In contrast to SK F 82526, SK F 87516 showed good natriuretic effects, but no significant antihypertensive effects in the conscious SHR after acute administration. SK F 85174 showed neither natriuretic nor antihypertensive activity after oral or i.p. dosing under these conditions. 

Calcium channel blockers have an intrinsic natriuretic effect therefore, they do not usually require the addition of a diuretic. These agents are useful in the treatment of hypertensive patients who also have asthma, diabetes, angina, and/or peripheral vascular disease. 

The ratio Na+/K+ is calculated for natriuretic activity. Values greater than 2.0 indicate a favorable natriuretic effect. Ratios greater than 10.0 indicate a potassium-sparing effect. 

Spironolactone, an aldosterone antagonist, is the drug of choice since secondary hyperaldosteronism often coexists in patients with hepatic ascites. Aldosterone is usually metabolised by the liver and is highly protein bound, therefore the free aldosterone levels are raised in cirrhosis. Spironolactone competes with aldosterone for receptor sites in the distal tubule, resulting in potassium retention and sodium and water loss. The initial dose of spironolactone is 100-200 mg and can be slowly increased according to response. There is a lag of 3-5 days between the beginning of spironolactone treatment and the onset of the natriuretic effect. 

FIGURE 19.8 The time course of furosemide concentration and natriuretic effect after 3 doses of 40 mg compared with those parameters after a single dose of 120 mg. Notice that the concentrations after 120 mg are exactly three times higher than after 40 mg, but the peak effect after 40 mg is quite close to the peak after 120 mg because the 120-mg dose is limited by effects approaching Emax- The cumulative sodium loss after 120 mg is 400 mmol, wliile the three 40-mg doses produce a 600-mmol loss. 

Natriuretic factors Animal experiments and clinical investigations point to the existence of these biochemical factors. After acute volume loading in healthy volunteers, it was possible to detect substances with a natriuretic effect in the blood and urine - yet this was not the case in cirrhotic and ascitic patients. 

A few isolated reports are available on the elimination of renal vasoconstriction, particularly using ANP (atrial natriuretic peptide) with its pronounced diuretic and natriuretic effects. 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

NSAIDs can interfere with fluid and electrolyte homeostasis, thereby causing edema, hyponatremia, hyperkalemia, and blunting of the natriuretic effects of diuretics (48,49). 

Several non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to interfere with the natriuretic effects of thiazides (SED-11, 423). A similar interaction is seen with tenidap, an antiarthritic cytokine modulating drug (46). The salt-retaining properties of the NSAIDs probably play the central role in this interaction. 

NSAIDs block the natriuretic effect of torasemide (SEDA-21, 229). 

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