Furosemide glomerular filtration

Another key feature of the thiazide-type diuretics is their limited efficacy in patients whose estimated renal function is reduced, such as the elderly. For example, patients with estimates of reduced renal function, such as those with a glomerular filtration rate (GFR) below 30 mL/minute, should be considered for more potent loop type diuretics such as furosemide. Clinicians often fail to either reconsider the role of thiazide diuretics prescribed to individuals whose renal function has been declining or fail to recognize the likely prevalence of renal compromise in the elderly to begin with. 

Furosemide and ethacrynic acid preserve glomerular filtration rate and are, therefore, the diuretic agents of choice in hypertensive patients with impairment of kidney function(17,18,... 

Furosemide is mainly excreted unchanged by glomerular filtration as well as tubular secretion. 

The sites of action within the kidney and the pharmacokinetics of various diuretic drugs are discussed in Chapter 15. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension and normal renal and cardiac function. More powerful diuretics (eg, those acting on the loop of Henle) such as furosemide are necessary in severe hypertension, when multiple drugs with sodium-retaining properties are used in renal insufficiency, when glomerular filtration rate is less than 30 or 40 mL/min and in cardiac failure or cirrhosis, in which sodium retention is marked. 

The loop diuretics are rapidly absorbed. They are eliminated by the kidney by glomerular filtration and tubular secretion. Absorption of oral torsemide is more rapid (1 hour) than that of furosemide (2-3 hours) and is nearly as complete as with intravenous administration. The duration of effect for furosemide is usually 2-3 hours and that of torsemide is 4-6 hours. Half-life depends on renal function. Since loop agents act on the luminal side of the tubule, their diuretic activity correlates with their secretion by the proximal tubule. Reduction in the secretion of loop diuretics may result from simultaneous administration of agents such as NSAIDs or probenecid, which compete for weak acid secretion in the proximal tubule. Metabolites of ethacrynic acid and furosemide have been identified, but it is not known if they have any diuretic activity. Torsemide has at least one active metabolite with a half-life considerably longer than that of the parent compound. 

Pathophysiology Non-potassium-sparing diuretics are the treatment of choice to reduce fluid retention and dyspnea. Acting at specific sites of nephrons, they inhibit sodium and water reabsorption. Loop diuretics act on the loop of Henle, producing a maximal diuretic effect equivalent to 20% to 25% of the filtered sodium load and promoting the free water clearance. Currently available loop diuretics include furosemide, bumetanide, torsemide, and ethacrynic acid. Because of their potency, they are generally effective in patients with advanced renal insufficiency (glomerular filtration rates <25 ml/min) (49). 

Acute renal insufficiency with severe hyponatremia has been attributed to vigorous diuretic treatment (metolazone, furosemide, spironolactone) with an ACE inhibitor (27). Because ACE inhibition impairs renal protection against reduced perfusion, the combination of an ACE inhibitor with high-dose furosemide causes a reduction in glomerular filtration rate linearly related to the change in blood pressure. 

A randomized, controlled study has shown an enhanced diuretic response to furosemide in infants taking theophylline during extracorporeal membrane oxygenation (49). The underlying mechanism was uncertain, but may have been an increase in glomerular filtration rate. 

Wright FS, Schnermann J. Interference with feedback control of glomerular filtration rate by furosemide, triflocin, and cyanide. JClin Invest 1974 53 1695-708. 

In most studies in which it has been investigated, ethacrynic acid administration results in a marked reduction in renal vascular resistance [13, 19-21]. However, this effect is nullified, as in the case with furosemide, by the superimposition of volume depletion [20-22]- Studies of bumetanide in the experimental animal have generally shown no change in GFR or renal plasma flow (RPF) [23, 24] except for transient acute increases in the latter which approximated 27 to 40%, declining later in the experiments to only modest elevations or to control levels [25,26]. In man, bumetanide is associated with either no change [27,28] or a 12 to 16% increase in effective renal plasma flow and glomerular filtration rate [29]. 

Burke TJ, Duchin KL Glomerular filtration during furosemide diuresis in the dog. Kidney Int 1979 16 672-680. 

Acetazolamide, and probably other diuretics which inhibit carbonic anhydrase, cause a strong inhibition of proximal NaHCOg reabsorption and lithium reabsorption. However, unlike loop diuretics, acetazolamide does not interfere with tubuloglomerular feedback and causes a 20% decrease in glomerular filtration rate. The increase in absolute lithium excretion is somewhat lower than that caused by loop diuretics [22]. Colussi et al. [25] reported the effect of furosemide and acefazola-mide to be additive, indicating a dual site of action (i.e., inhibition of lithium reabsorption in both the proximal tubule and the loop of Henle). 

When renal function is compromised, treatment involves the use of drugs to increase RBF, glomerular filtration rate (GFR) and urine output. In equine patients with acute renal failure (ARF), furosemide (frusemide), dopamine and mannitol (Table 10.1) are the most common drugs utilized Qose-Cunilleras Hinchcliff 1999). 

The concurrent use of an organic anion and methotrexate enhances the toxicity of methotrexate. The toxicity of gentamicin (excreted by glomerular filtration) is enhanced by the presence of dehydration or the concurrent use of furosemide. 

In most studies in which it has been investigated, ethacrynic acid administration results in a marked reduction in renal vascular resistance [7, 13-15]. However, this effect is reversed as in the case of furosemide, by the development of volume depletion [14-16]. Studies of bumetanide in the experimental animal have generally shown no change in glomerular filtration rate... 

No. Neither renal blood flow or glomerular filtration rate (GFR) are affected. This is in contrast to furosemide and bumetanide, both of which increase renal blood flow (RBF). 

There are no methods known to accelerate the active transport of poisons into urine, and enhancement of glomerular filtration is not a practical means to facilitate elimination of toxicants. However, passive reabsorption from the tubular lumen can be altered. Diuretics inhibit reabsorption by decreasing the concentration gradient of the drug from the lumen to the tubular cell and by increasing flow through the tubule. Furosemide is used most often, but osmotic diuretics also are employed ("see Chapter 28). Forced diuresis should be used with caution, especially in patients with renal, cardiac, or pulmonary complications. 

Tilstone WJ, Semple PF, Lawson DH, Boyle JA. Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine and gentam icin. Clin Pharmacol Ther( 9H) 22,389-94. 

In a small, placebo-controlled, crossover study in 8 healthy subjects, ibuprofen 400 mg and 800 mg three times daily for 3 days significantly reduced the glomerular filtration rate and the diuresis produced by a single 20-mg intravenous dose of furosemide, but did not alter sodium excretion. ... 

Two elderly women with congestive heart failure did not respond to treatment with furosemide and digoxin until the naproxen they were taking was withdrawn. A single-dose study in patients with heart failure found that the volume of urine excreted in response to furosemide was reduced about 50% by naproxen. 3 jjj placebo-controlled study, 6 patients with cirrhosis and ascites were given a single 40-mg intravenous dose of furosemide before and after naproxen 500 mg twice daily for 5 doses. It was found that this short-term use of naproxen reduced the glomerular filtration rate and the natriuretic and diuretic effects of furosemide. ... 

A study in 8 healthy subjects found that nimesulide 200 mg twice daily attenuated the effects of furosemide 40 mg twice daily. Subj ects who had initially lost weight when taking furosemide regained weight, diuresis was slightly reduced, and the glomerular filtration rate was reduced. 

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