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PubMed2000

[Non-steroidal anti-inflammatory agents and diuretics: a combination with nephrotoxic risks].

We report the case of a reversible postoperative acute renal failure in a 55-year-old woman without preoperative risk factors who underwent a retinal surgery. The association of diuretics with nonsteroidal antiinflammatory drugs was probably responsible of an ischaemic acute tubular necrosis. Vitreoretinal surgery's postoperative period might be associated with a specific risk for the kidney because of an usual intensive diuretic prescription. Nonsteroidal antiinflammatory drugs should be avoided if possible in this indication.

Acute Kidney Injury↗
PubMed2001

Changes in the phamacologic treatment of hypertension in the Department of Veterans Affairs 1997-1999: decreased use of calcium antagonists and increased use of beta-blockers and thiazide diuretics.

Older studies of antihypertensive treatment have shown that prescribing patterns are not consistent with recommendations from expert national panels. We determined whether prescribing patterns for antihypertensive drugs changed recently in the largest integrated health care system in the United States. Specifically, we determine 1) patterns of antihypertensive medication use at all Department of Veterans Affairs (VA) medical facilities for fiscal years 1997 to 1999, 2) the cost of this care, and 3) savings associated with changes in treatment patterns. Data were aggregated by individual medication as well as by antihypertensive drug class. Estimates of VA national antihypertensive drug costs are based on the median cost and the number of units for each dosage form of each medication dispensed at all facilities. At VA medical facilities, calcium antagonist use went from 33% to 29.3% of antihypertensive treatment days between 1997 and 1999, angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use from 36.4% to 36.8%, beta-blockers from 19.1% to 21.1%, and thiazide diuretic use from at 11.5% to 12.8%. If treatment patterns had remained the same between 1997 and 1999 in terms of the proportion of medications from each drug class, an additional six million dollars would have been spent on antihypertensive medications in 1999. Although calcium antagonists and ACE inhibitors/ARB remained the most commonly dispensed antihypertensives at VA facilities from 1997 to 1999, there was a proportional decrease in calcium antagonist use and an increase in the use of thiazide diuretics and beta-blockers. These changes were consistent with improved compliance with VA national guidelines. The cost implications of these changes in practice patterns were considerable.

Adrenergic beta-Antagonists↗
PubMed2000

Fibrinolytic function in diuretic-induced volume depletion.

Accumulating evidence suggests that the renin-angiotensin system (RAS) may participate in the regulation of fibrinolytic function. In clinical studies, however, angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor antagonist losartan have failed to consistently affect endogenous fibrinolysis. Because such an effect may depend on the degree of prestimulation of the RAS, we have studied parameters of fibrinolytic function in 15 healthy volunteer subjects during baseline (day 1) and after 10 days of treatment with 25 mg of hydrochlorothiazide (HCT)/day (day 11). On the last day of the study (day 12), a single oral dose of 50 mg of losartan was given to the volunteers in addition to HCT and fibrinolytic function was assessed at the peak effect of losartan (5 h later). Plasma renin activity (PRA) was significantly stimulated during diuretic treatment (1.35 +/- 0.21 v 0.34 +/- 0.06 ng mL(-1) x h(-1) [P < .001]) and further increased after losartan (6.39 +/- 1.16 ng mL(-1) x h(-1) [P < .001]). No effects of either the diuretic or losartan could be observed on tissue-type plasminogen activator (t-PA) antigen concentration and activity. However, 10 days of treatment with HCT significantly increased plasminogen activator inhibitor-1 (PAI-1) antigen (26.8 +/- 5.8 v 21.1 +/- 3.4 ng/mL [p = .037]). In addition, PAI-1 activity was also tentatively raised by HCT treatment (5.48 +/- 1.82 v 3.88 +/- 0.79 IU/mL [P = .067]). In spite of the marked further rise in PRA after losartan, the stimulation of PAI-1 antigen and activity was blunted by losartan (24.4 +/- 3.6 ng/mL and 4.55 +/- 0.99 IU/mL, respectively). Our results demonstrate that volume depletion induced by HCT treatment is associated with a rise in PAI-1. Acute administration of losartan is capable of blunting this effect, suggesting that the angiotensin II type 1 receptor may participate in this effect of angiotensin II.

Adult↗
PubMed1999

Diuretic activity of an aqueous extract of Phyllanthus sellowianus.

Phyllanthus sellowianus Muell. Arg. (Euphorbiaceae) is used widely as a hypoglycemic and diuretic agent in South American folk medicine. In order to assess the diuretic activity of this plant, test animals were treated with a single oral administration of an aqueous extract (5% w/v) of the stem bark of P. sellowianus (400 mg/kg body weight), which produced after 8 h a significant increase in the urinary excretion. In the studies on acute toxicity in mice neither mortality nor neurobehavioral or autonomic profile changes could be observed.

Animals↗
PubMed1994

Column-switching techniques for screening of diuretics and probenecid in urine samples.

A method based on high-performance liquid chromatography using column-switching is described for the screening of diuretics and probenecid in urine samples. The system uses a 20- x 2.1-mm i.d. precolumn, packed with a Hypersil ODS-C18, 30-microns stationary phase, for the on-line sample cleanup and enrichment. Untreated urine samples are directly injected, and the precolumn is flushed for 1 min with water to eliminate polar matrix components. The retained analytes are then back-flushed by means of a six-port switching valve onto a Hypersil ODS-C18 analytical column (5 microns, 250- x 4-mm i.d.), where they are separated using an acetonitrile/phosphate buffer (pH = 3) gradient elution. Under these conditions, the separation and identification of diuretics and probenecid can be achieved with satisfactory selectivity and sensitivity. The described procedure is very simple and rapid since no off-line manipulation of the sample is required, the total analysis time being ca. 15 min.

Chromatography, High Pressure Liquid↗
PubMed1981

(Acylaryloxy)acetic acid diuretics. 4. Indeno[5,4-b]furan-2-carboxylic acids.

Investigation of the chemistry of the potent new uricosuric diuretic indacrinone (MK-196) led to a class of novel annulated derivatives, indeno[5,4-b]furan-2-carboxylic acids. The structural requirements for optimal diuretic and uricosuric activity of the tricyclic analogues differed from those of their (indanyloxy)acetic acids counterparts. Most notably, the tricyclic analogues were two to four times more natriuretic than the corresponding (indanyloxy)acetic acids when administered orally to rats, and in chimpanzees, uricosuria was observed only in those indenofurans having a nuclear aryl substituent.

Animals↗
PubMed1978

(Acylaryloxy)acetic acid diuretics. 2. (2-Alkyl-2-aryl-1-oxo-5-indanyloxy)acetic acids.

The introduction of an aryl group at the 2 position of the uricosuric diuretics, (1-oxo-2-alkyl-5-indanyloxy)acetic acids, provided compounds with markedly increased potency over their monosubstituted precursors. These compounds were synthesized either by arylation of the corresponding 2-alkyl-5-methoxy-1-indanones with diaryliodonium salts or by alkylation of the 2-aryl-5-methoxy-1-indanones which were cleaved to the corresponding phenols and then converted to the desired oxyacetic acids. Systematic structural variation of the 2-arylindanyloxyacetic acids provided aryl-substituted compounds with varying degrees of uricosuric and diuretic activity.

Acetates↗
PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 2. (4-(3-Oxo-1-alkenyl)phenoxy)acetic acids.

A series of (E)-[4-(3-oxo-1-alkenyl)phenoxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic properties. Several compounds exhibited noteworthy activity, e.g., (E)-[2,3-dichloro-4-(3-oxo-1-butenyl)phenoxy]acetic acid (3a). While possessing only half of the dose potency of ethacrynic acid (2), the active compounds act similarly to this diuretic in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Potassium ion excretion is increased but less markedly than sodium excretion.

Acetates↗
PubMed1983

Heterocyclic oxyacetic acid diuretics: indazole, benzisothiazole, and benzisothiazole 1,1-dioxide analogues of [[7-chloro-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid.

The indazole, benzisothiazole, and benzisothiazole 1,1-dioxide analogues of [[7-chloro-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid were synthesized and tested for diuretic activity in saline-loaded mice. Each analogue was found to be less active than the parent benzisoxazole: the diuretic activity followed the order O greater than S greater than N = SO2 in regard to the heteroatom in the 1-position of the ring.

Animals↗
PubMed1984

[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 1. Effects of nitrogen and aromatic nuclear substitution.

A series of Mannich bases and aminomethyl derivatives of ethyl [2,3-dichloro-4-(4-hydroxybenzoyl)phenoxy]acetate were synthesized and tested for saluretic and diuretic activities. The effects of nitrogen and aromatic nuclear substitution, reorientation of the aminomethyl group relative to that of the phenolic hydroxyl group, and replacement of either the phenolic hydroxyl or the aminomethyl group by other functional groups are described. Ethyl [2,3-dichloro-4-[3-(aminomethyl)-4-hydroxybenzoyl]phenoxy]acetate (27) was found to be a very potent, high-ceiling diuretic.

Administration, Oral↗
PubMed1984

[(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 2. Modifications of the oxyacetic side chain.

The discovery of high-ceiling natriuretic activity from a series of aminomethyl derivatives of ethyl [2,3-dichloro-4-(4-hydroxybenzoyl)phenoxy]acetate prompted our continued investigation of this new class of (aryloxy)acetic acid diuretics. Systematic alteration of the oxyacetic side chain has shown that the carboxylic acid function is the active species in vivo and that the ethyl ester group serves as a prodrug to enhance oral absorption. Side-chain functional groups that are incapable of generating the carboxylic acid in vivo failed to impart diuretic activity to the target compounds. Additional side-chain modifications including homologation, methyl substitution, and heteroatom replacement are also described. Ring annelation of the oxyacetic side chain to a dihydrobenzofuran-2-carboxylic acid produced compound 32, which displayed the highest level of saluretic activity for this series.

Administration, Oral↗
PubMed2000

Loop diuretics inhibit detubulation and vacuolation in amphibian muscle fibres exposed to osmotic shock.

The effect of loop diuretics at concentrations known to influence cellular water entry coupled to Na-K-Cl co-transport, upon the vacuolation and detubulation following osmotic shock, was investigated in amphibian skeletal muscles. These were exposed to a glycerol-Ringer solution (18 min), an isotonic Ca2+/Mg2+ Ringer solution and cooling. Adding bumetanide (1.0 and 2.0 microM) to these solutions sharply reduced the incidence of detubulation, assessed by abolition or otherwise of action potential after-depolarisations, from 93.9 +/- 4.7% (n = 6) to 5.0 +/- 1.1% (n = 4: mean +/- SEM: 2.0 microM bumetanide). It dramatically reduced the number and fraction of muscle volume occupied by tubular vacuoles, measured using confocal microscopy, from 60.3 +/- 4.3% (n = 10) to 9.0 +/- 1.1% (n = 35). The incidence of large horseradish peroxidase-lined tubular vacuoles, viewed using electronmicroscopy, similarly was reduced with 2 microM bumetanide in the glycerol-Ringer solution. Bumetanide acted through cellular volume adjustments early in the detubulation protocol. Thus, it exerted its maximum effect when added to the glycerol-Ringer, rather than the Ca2+/Mg2+ Ringer solution. Furthermore, whereas fibre diameters measured using scanning electron microscopy returned to normal during glycerol treatment relative to those of control fibres left in isotonic Ringer, addition of 2.0 microM bumetanide in the glycerol Ringer left markedly smaller fibre diameters. Finally equipotent concentrations of the chemically distinct loop diuretics. furosemide and ethacrynic acid similarly influenced detubulation. These findings implicate Na-K-Cl co-transport in the water entry into muscle fibres that would be expected following introduction of extracellular glycerol. This might then enable the subsequent Na-K-ATPase dependent water extrusion that produces the tubular distension (vacuolation) and detachment (detubulation) following glycerol withdrawal, phenomena also observed in muscular dystrophy.

Action Potentials↗
PubMed1997

Diuretics in the prevention and treatment of congestive heart failure.

Diuretics, either as monotherapy or in combination with other drugs in the management of hypertension, have retarded the development of left ventricular hypertrophy and congestive heart failure in many patients. Diuretics also remain one of the most effective therapies in the treatment of congestive heart failure, when given with an ACE inhibitor and digoxin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Interactions of aldosterone antagonist diuretics with human serum proteins.

PURPOSE: The purpose of this study was to investigate the binding mechanism of aldosterone antagonist diuretics with human serum proteins, human serum albumin (HSA) and alpha 1-acid glycoprotein (AGP), as well as to identify the binding sites of the drugs on these proteins. METHODS: Binding activities of spironolactone (SP) and its pharmacologically active metabolite canrenone (CR) to serum and serum protein were examined by ultrafiltration and spectroscopic techniques. The data for the binding of these drugs to HSA were analyzed on the basis of a theoretical model of simultaneous binding of the ligands. RESULTS: The binding percentages of antagonist diuretics SP and CR to human serum proteins were 88.0% and 99.2%, respectively, at therapeutic concentrations. SP bound strongly only to HSA. In addition, the displacement results found using fluorescent probes and ultrafiltration methods demonstrated that SP bound to site I, particularly to the warfarin region on HSA, and to the basic binding site on AGP, while CR bound to the warfarin region on HSA. CONCLUSIONS: The limited results presented here stress the need for caution on coadministration of acidic drugs which bind to the warfarin region on HSA and basic drugs which bind to AGP with SP and its metabolite CR.

Blood Proteins↗
PubMed2002

[Long-term diuretic treatment in heart failure: are there differences between furosemide and torasemide?].

BACKGROUND: Treatment for congestive heart failure (CHF) is an important factor in rising health care costs especially in patients requiring repeated hospitalisations. Diuretics remain the most frequently utilized drugs in symptomatic patients. In this study the long-term outcome under furosemide and torasemide, two loop diuretics with different pharmacokinetic properties, were evaluated during one year in an ambulatory care setting. AIMS: Comparison of hospitalization rates and estimated costs under long-term treatment with furosemide and torasemide in patients with CHF. METHODS: Retrospective analysis of disease course and resource utilization in 222 ambulatory patients receiving long-term treatment with furosemide (n = 111) or torasemide (n = 111). Data were also compared to those of a similar study including 1000 patients in Germany. RESULTS: Patients receiving long-term treatment with torasemide had a lower hospitalisation rate (3.6%) compared to patients on furosemide (5.4%). Corresponding hospitalization rates in the German study were 1.4% under torasemide and 2% under furosemide. The higher hospitalisation rates in Swiss patients could be explained by a higher average age (75 years vs. 69 years) and a longer duration of symptomatic heart failure (4.1 yrs vs. 0.7 yrs). Cost estimates based on the average number of hospital days (0.54 under torasemide compared to 1.05 under furosemide) indicated that the financial burden could be halved by a long-term torasemide treatment. CONCLUSION: Torasemide with its more complete and less variable bioavailability offers potential clinical and economic advantages over furosemide in the long-term treatment in patients with CHF.

Adult↗
PubMed2001

Diagnosis of kidney transplant obstruction using Mag3 diuretic renography.

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long-term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium-99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n = 21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n = 43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6 +/- 18.9 vs. 81.6 +/- 5.4%, p < 0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9 +/- 4.1 vs. 3.6 +/- 1.5 min, p < 0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to < 75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold-up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of > 5 min and a TTB of > 7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.

Adult↗
PubMed1981

Addition of acebutolol to diuretics in hypertension.

The effect of acebutolol as an antihypertensive beta receptor-blocking drug was evaluated in 15 patients that remained hypertensive while on diuretics. Observations were made in a small randomized double-blind trial in which the drug was compared to placebo and subsequently during a single-blind phase when the drug was given to those who had not responded to placebo. The dose range for acebutolol was 200 to 600 mg twice daily. Pretreatment plasma renin activity (PRA) and the response to intravenous saralasin infusion were assessed as predictors of the antihypertensive effect of acebutolol. None of six patients receiving placebo had a response of goal blood pressure or below; six of nine receiving acebutolol did respond (P less than 0.01). Acebutolol treatment induced reduction in diastolic pressure, heart rate, and PRA pooled from both phases of the study. There were no significant correlations between acebutolol therapy. Our data indicate that acebutolol is effective in diuretic-resistant hypertensive patients and that indices of the renin-angiotensin system are not predictors of the therapeutic response.

Acebutolol↗