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PubMed1994

[Role of diuretic dynamic echography in the study of the pyelo-ureteral junction: review of a caseload after the first 4 years of experience].

Diuretic ultrasound, described in Literature in the seventies from Rosenfield, is an effective technique if compared with the functional urodynamic study and the diuretic renography evaluation for the assessment of upper urinary tract obstruction. In our study we have compared the effectiveness of diuretic ultrasound with diuretic intravenous urography in the evaluation of obstructive pathology of ureteropelvic junction. The technique was performed on 47 patients 11 of whom were pediatrics making a total of 94 renoureteric units. Results show high sensibility of this technique either with severe obstructions (94%) or moderate obstructions (96%).

Adolescent↗
PubMed2002

Diuretic Doppler ultrasonography in chronic unilateral partial ureteric obstruction in dogs.

OBJECTIVE: To compare the effects of diuresis induced by a loop diuretic (frusemide), an osmotic diuretic (mannitol) and a high-osmolar radio-contrast medium (sodium iothalamate) on the intrarenal resistive index (RI) in dogs with chronic unilateral partial ureteric obstruction (UPUO). MATERIALS AND METHODS: The split renal clearance and intrarenal RI were estimated in 11 dogs with chronic UPUO. Doppler ultrasonography measurements of the interlobar arteries were obtained before and 10 min after the intravenous infusion of 1 mg/kg frusemide, 1 g/kg mannitol or 20 mL 60% sodium iothalamate. The same experimental protocol was repeated with another drug at 1-week intervals. RESULTS: There was a significant difference between the intrarenal RI of obstructed and unobstructed kidneys in the chronic phase of UPUO. While mannitol and sodium iothalamate significantly increased the RI in both kidneys, differences in RI between the kidneys decreased after infusing the two drugs. However, while frusemide insignificantly increased the RI in the obstructed kidney, it decreased the RI in unobstructed one. Consequently, the difference in RI between the kidneys increased significantly after administering frusemide. There were no significant differences in urinary volume after administering each of the drugs. CONCLUSIONS: As there were no significant differences in the diuretic effects of the drugs, frusemide may have additional effects on the RI of unobstructed kidneys other than diuresis. Frusemide increased the difference between the intrarenal RI of the kidneys and therefore may improve the detection of unilateral urinary obstruction in humans.

Animals↗
PubMed1976

Diuretic agents. Mechanisms of action and clinical uses.

Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure.

Acute Kidney Injury↗
PubMed1964

RESPONSE OF THE INFANT KIDNEY TO DIURETIC DRUGS.

The diuretic response of normal infants, 6 to 47 days of age, to single doses of mercaptomerin, chlorothiazide, acetazolamide, triamterene and spironolactone was studied by following urinary electrolytes, pH and osmolality. Peak diuresis occured two to four hours after drug administration, and because of compensatory mechanisms little change in urinary excretion was found if only 24-hour urines were studied. Mercaptomerin increased sodium excretion seven-fold, compared to three- to four-fold increases for the other diuretics. Control urinary Na:K ratios averaged 0.68 in infants compared to 2.8 for adults, and mercaptomerin produced the largest increase in this ratio. Qualitatively the response to diuretics is the same in newborn in the ages studied as it is reported to be for adults; no immaturity of the infant kidney in this regard was demonstrated.

Acetazolamide↗
PubMedDate not supplied

Can we improve diuretic response in heart failure?

Although there have been major advances in the treatment of heart failure, loop diuretics remain essential for the treatment of fluid retention. Patients with refractory heart failure become resistant to progressively larger doses of diuretics. Some of the strategies which may be helpful in restoring diuretic efficacy are reviewed.

Benzothiadiazines↗
PubMed2003

Do thiazide diuretics confer specific protection against strokes?

Several large studies have suggested that therapy with thiazide diuretics confers a particular benefit in reducing the risk of strokes that seem to be, at least to some extent, independent of the blood pressure-lowering effect. Such a cerebroprotective effect was documented not only with monotherapy but also when diuretics were used in combination with other drugs. The cerebroprotective effect does not seem to be shared by other drug classes, such as the beta-blockers or the angiotensin-converting enzyme inhibitors, in patients without manifest cardiovascular disease. Since stroke is one of the most devastating sequelae of high blood pressure, our data strongly favor the use of low-dose diuretics either as initial therapy or in combination in all hypertensive patients at risk for cerebrovascular disease.

Antihypertensive Agents↗
PubMed2004

Synthesis and evaluation of some novel quinazolinone derivatives as diuretic agents.

A new series of quinazolin-4(3H)-one derivatives containing either a thiazole or a 1, 3, 4-thiadiazole moiety were prepared in order to study the effect of such a heterocyclic combination on the expected diuretic activity. Synthesis of the target compounds (2, 4, and 6) has been achieved through an interaction of the starting 7-chloro-2-methyl-4H-3, 1-benzoxazin-4-one 1 with different heterocyclic amines. Alkylation of 3-(2-mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivative 4 with different alkyl halides or chloroacetic acid afforded the corresponding thioethers 5 while interaction of 2-methyl-3-(1, 3, 4-thiadiazol-5-yl or thiazol-5-yl)quinazolin-4(3H)-ones (2 and 6) with various aromatic aldehydes resulted in the formation of the arylvinyl analogs 3 and 7, respectively. On the other hand, 2-morpholinomethyl-3-(2-sulfamoyl or mercapto-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one derivatives 10 have also been synthesized through an interaction of the sulfonamide or thiol analog 9 with the appropriate amine. Biological evaluation of some of the target compounds as diuretic agents was carried out. The results showed that 2-[2-(4-chlorophenyl)vinyl]-7-chloro-3-(2-sulfamoyl-1, 3, 4-thiadiazol-5-yl)quinazolin-4(3H)-one 7b exhibited significant diuretic activity. The detailed synthesis, spectroscopic and biological data are reported.

Animals↗
PubMed1978

Ticrynafen, a uricosuric antihypertensive diuretic.

Ticrynafen, a diuretic-uricosuric also effective as an antihypertensive, was compared in single doses with several other diuretics. Over an 8-hr period, a 250- mg dose exerted natriuretic activity comparable to that of 25 mg of chlorthalidone and 50 mg of ethacrynic acid; a 500-mg dose was comparable to 50 mg chlorthalidone and 50 mg hydrochlorothiazide. Ticrynafen combined with furosemide had an additive effect, whereas a combination with hydrochlorothiazide was not additive. In both doses ticrynafen was a uricosuric and this effect was maintained when given with furosemide and hydrochlorothiazide, both of which individually were slightly antiuricosuric. Ticrynafen may be useful in patients requiring a diuretic in whom it is desirable to avoid hyperuricemia.

Adult↗
PubMed1995

Spontaneous bacterial peritonitis in cirrhotic patients treated using paracentesis or diuretics: results of a randomized study.

Diuretic treatment in cirrhotic patients with ascites increases ascitic fluid concentration of total protein and complement components, and opsonic activity. These changes are not observed in patients treated with paracentesis. Based on these data it has been suggested that therapeutic paracentesis may be associated with an increased risk of spontaneous bacterial peritonitis (SBP) development. To assess this possibility, 80 cirrhotic patients with tense ascites were randomly allocated in two therapeutic groups: group 1 (40 patients) was treated with total paracentesis associated with plasma volume expansion and group 2 was treated with diuretics. After mobilization of ascites, patients from both groups received diuretics to avoid reaccumulation of ascites; cases that developed tense ascites during follow-up (mean follow-up period, 60 +/- 6 and 55 +/- 4 weeks, respectively) were treated according to initial randomization. Patients from both groups had similar results regarding baseline clinical and standard laboratory data, ascitic fluid concentration of total protein, complement components, and opsonic activity. Sixteen patients (7 from group 1 and 9 from group 2) developed SBP during the study period. The 4-week and 1-year probability of SBP occurrence were 2.5% and 18.6%, respectively, in group 1 patients, and 11.9% and 24%, respectively, in group 2 patients. Therefore, our study indicates that therapeutic paracentesis does not increase the early- and long-term risk of SBP development in cirrhotic patients with tense ascites.

Ascites↗
PubMedDate not supplied

Sites and mechanisms of action of diuretics in the kidney.

Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four kinds of observations: (1) the effects of diuretic agents on the concentrating and diluting mechanism; (2) an analysis of the pattern of anionic excretion produced by the drug; (3) determination of the action of the agent on acid excretion and on acid-base status; (4) an evaluation of the effects of the diuretic on potassium excretion. Agents (such as acetazolamide) that act in the proximal convoluted tubule cause an enhancement of solute-free water generation (CH2O), induce a phosphaturia and an increase in bicarbonate excretion, alkalinize the urine, and cause a kaliuresis. Those agents which inhibit sodium chloride transport in the loop of Henle (for example, furosemide and ethacrynic acid) reduce both CH2O and the abstraction of tubular water from the collecting duct (TCH2O). They are the most potent natriuretic agents currently available, causing increments in the excretion of sodium in the urine of 15 to 25 per cent of filtered load. Those drugs which act in the early portion of the distal convolution (the thiazides, metolazone) reduce CH2O modestly or not at all and have no effect on TCH2O. They are capable of increasing urinary sodium by 5 to 8 per cent of the filtered load. The special-purpose agents such as triamterene and spironolactone are only mildly effective as natriuretic agents. While they augment fractional sodium excretion by only 2 to 3 per cent, they are useful because of their capacity to reduce urinary potassium excretion, either by a direct renal tubular effect (triamterene) or by competitive inhibition of aldosterone (spironolactone).

Bicarbonates↗
PubMedDate not supplied

Effects of loop diuretics on carbohydrate metabolism and electrolyte excretion.

The effects of two loop diuretics, bumetanide and furosemide, on carbohydrate metabolism and electrolyte balance were assessed in 11 normal male subjects in a double-blind manner. Glucose, insulin, glucagon, and growth hormone responses to 5-hour glucose tolerance test and arginine infusion were measured during the control and drug treatment periods. Three other non-insulin-dependent diabetic subjects, receiving diuretic drug for six weeks, underwent a similar protocol. Kaliuresis and natriuresis due to diuretic administration were significant only on day 1 of treatment. There were no significant changes in total body potassium by 40K counting; net potassium loss by balance study was minimal in both the acutely treated subjects and the chronically treated patients. Effects of bumetanide and furosemide on water and electrolyte excretion did not differ. Glucose tolerance was significantly improved with bumetanide but not with furosemide. Plasma insulin, glucagon, and growth hormone levels during the oral glucose tolerance test were unaffected by either drug. Insulin levels with arginine infusion were significantly increased, and growth hormone levels decreased with bumetanide but not with furosemide. No evidence of impaired carbohydrate metabolism in the three chronically treated diabetic subjects was seen. It is concluded that the effects of bumetanide and furosemide on potassium balance and glucose utilization were minimal in this experimental setting.

Adolescent↗
PubMedDate not supplied

Bumetanide: a new diuretic. Results of clinical efficacy and safety in patients with congestive heart failure.

A clinical study of bumetanide, a new diuretic, was conducted in outpatients of a cardiology clinic to determine its long-term effectiveness and safety in the treatment of peripheral edema due to congestive heart failure. The drug was administered for at least 24 weeks on a selected group of 34 patients. The patients were monitored for clinical response, evidenced by changes in cardiac signs and symptoms, and by laboratory tests, as well as by slit-lamp ophthalmic examination, electrocardiogram, and chest x-ray. Based on the clinical evaluation of effects on body weight, chronic edema, functional physical capacity, and results of selected laboratory data, it was concluded that bumetanide is as effective as other diuretics and can be used as an initial diuretic for maintenance of body weight for long-term use in patients with peripheral edema due to congestive heart failure. Bumetanide mobilizes peripheral edema effectively in most patients and leads to improvement in functional physical capacity. Safety and adverse reactions during treatments are discussed.

Aged↗
PubMed1988

Pharmacologic effects of A-56234, a new high-ceiling diuretic.

The pharmacokinetic characteristics, the diuretic, saluretic, and uricosuric properties, and the safety of single, rising, oral doses of A-56234, a new high-ceiling diuretic, were evaluated in this double-blind, placebo-controlled, cross-over study. Each of three groups of eight subjects received placebo and three different single doses of the diuretic at 1-week intervals. Doses ranged from 0.5 to 80 mg. Significant, dose-related increases in urine volume and in urinary excretion of sodium and chloride were produced during the 24 hours after administration of 20, 40, 60, and 80 mg of the drug. Uricosuria was not observed at any dose. The drug was rapidly absorbed and displayed linear pharmacokinetics within the dose range studied. The elimination-phase plasma half-life was approximately 6 hours. Hepatic clearance was the main route of excretion in humans; only 2 to 10% of the parent drug was excreted in the urine. The drug was well tolerated and no clinically important adverse events were noted.

Adolescent↗
PubMedDate not supplied

Piretanide: a loop-active diuretic. Pharmacology, therapeutic efficacy and adverse effects.

Piretanide is a high-ceiling, loop-active diuretic that has been developed for treatment of congestive heart failure, hypertension and edematous states caused by renal and hepatic diseases. Piretanide is structurally related to furosemide and bumetanide; when administered orally, 6 mg of piretanide is as effective as 40 mg of furosemide, and when administered intravenously, 12 mg of piretanide is as effective as 40 mg of furosemide. Piretanide enhances water and sodium excretion in patients with congestive heart failure, with nephrotic syndrome and with cirrhosis and ascites. Adverse effects reported to date are limited to those attributable to excess loss of fluid and electrolytes. Under some conditions, piretanide appears to be less potassium wasting than thiazide diuretics or other loop-active diuretics.

Animals↗
PubMed1977

Renal function testing: differentiation between a nephrotoxic agent and diuretic drugs.

Preliminary studies indicate that it may be possible to differentiate the effects of a nephrotoxic substance from those of diuretic agents by the measurement of both urine and plasma osmolarity. The nephrotoxic substance, mercuric chloride, decreases urinary osmolality and increases plasma or serum osmolality. The diuretic agents, at exceedingly high dosages, may show a dose-related decrease in urine osmolality. However, serum osmolality either remains unchanged or is only slightly lowered. This difference in the serum response of animals treated with a nephrotoxin or diuretic agents may allow for the differentiation in toxicological studies.

Acetazolamide↗
PubMed1991

Comparative acute ototoxicity of loop diuretic compounds.

A microelectrode was used to measure endocochlear potentials (EP) in adult chinchillas and to study the effects of a series of loop diuretics. EP was measured before, during and for several hours after the intravenous injection of the following loop diuretics: furosemide, piretanide, bumetanide, ethacrynic acid, indacrinone stereoisomers and ozolinone. The first four loop diuretics caused a substantial dose-related reduction of EP. The (-) isomer of indacrinone was found to cause a dose-related reduction of EP to a moderate degree. The (+) isomer of indacrinone and ozolinone caused very little change of EP, even in very high doses. Findings are consistent with data on the mechanism of action of these agents in the kidney.

Acute Disease↗
PubMed1994

Vascular effects of loop diuretics: an in vivo and in vitro study in the rat.

The vascular effects of loop diuretics were studied in two models designed to eliminate hemodynamic repercussions linked to sodium and water depletion: in vivo, in unilaterally nephrectomized rats with a contralateral uretero-venous shunt, and in vitro, in the isolated perfused rat kidney. In anesthetized rats, local vascular resistance was calculated from the simultaneous recording of blood pressure and renal, iliac and carotid blood flows (electromagnetic flowmeter, Skalar). Furosemide and piretanide (10 to 80 mg/kg i.v.) induced a comparable dose-dependent decrease in renal vascular resistance, which was not modified by reserpine and indomethacin pre-treatment. The iliac relaxing response was blunted by vasoconstriction, which disappeared after combined treatment with reserpine and indomethacin. The relaxation induced in the iliac and carotid vasculature persisted after bilateral nephrectomy. In vitro, the vasorelaxing effect of diuretics in isolated rat kidneys perfused in an open circuit was studied after vascular tone had been re-established by a continuous perfusion of PGF2 alpha. Furosemide, piretanide and ozolinone induced a concentration-dependent decrease in renal tone (EC50 = 0.47 x 10(-4) mol/l, 1.03 x 10(-4) mol/l and 2.07 x 10(-4) mol/l respectively) in Wistar rats. A similar response to piretanide was found in spontaneously hypertensive stroke-prone rats (EC50 = 0.32 x 10(-4) mol/l) and in their normotensive controls (EC50 = 0.74 x 10(-4) mol/l). Our results show that loop diuretics induce a direct relaxation in the renal, iliac and carotid vasculature. This vascular effect, which appears at relatively high concentrations of the drugs, is prostaglandin independent and persists after bilateral nephrectomy.

Animals↗
PubMed1984

Mechanism, regulation and physiological significance of the loop diuretic-sensitive NaCl/KCl symport system in animal cells.

Investigations in numerous laboratories have characterized a salt transport system, present in many animal cell types, which catalyzes the transmembrane transport of NaCl and KCl in a tightly coupled process. The system is inhibited by loop diuretics such as furosemide and bumetanide. This transport system has been designated the loop diuretic-sensitive NaCl/KCl symporter. It has been implicated in transepithelial salt secretion and absorption as well as in cell volume regulation, and it may be defective in patients suffering from essential hypertension. This review serves to evaluate research conducted to date regarding the mechanism, mode of regulation, and physiological significance of the transport system. Ion binding specificities and absolute binding constants for all three naturally occurring ions have been determined in one cell system, the MDCK kidney epithelial cell line. In that same cell line, substrate binding was shown to exhibit apparent cooperativity. although a few reports suggest unidirectional transport of ions via this system under certain conditions, the consensus of reports indicates fully reversible, bidirectional salt transport with the direction of net flux determined by the magnitudes of the gradients of the three transported ions. Growth of cells in media containing a low concentration of K+ (less than 0.25 mM) allows selection of mutants lacking or defective in the symporter. Kinetic analyses with the MDCK cell line have shown that the symporter catalyzes accelerative exchange transport. However, exchange transport of one ion in the absence of one of the other two ionic substrates has not been documented. Comparison with other well-characterized transmembrane transport systems has shown that the characteristics of the NaCl/KCl symporter most resemble those of two-species facilitators (chemiosmotically-coupled symporters) found in prokaryotes and eukaryotes alike. these two-species facilitators consist of a single transmembrane protein and may function by a carrier-type mechanism as originally proposed by Peter Mitchell. A molecular model for the NaCl/KCl symporter is presented and discussed. Activation of symport activity requires ATP and probably occurs by a protein kinase-catalyzed mechanism. In some cell types activation is cyclic AMP dependent. ATP hydrolysis is not stoichiometric with transport. Phosphorylation of an integral membrane protein with an apparent size of 240 000 daltons correlates with activation of transport. It is postulated that this protein is the loop diuretic-sensitive NaCl/KCl symporter.

Adenosine Triphosphate↗