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Introduction: The extremity edema of advanced disease is a common, multifactorial feature, which impairs patients' activities and quality of life. The most frequently chosen management is based on combined decongestive physiotherapy or pharmacotherapy (with diuretics or steroids). Subcutaneous lymphatic drainage in refractory edema may decrease the swelling, prevent spontaneous lymphorrhea, but also increase the risk of infection. Safe and effective conservative management in diuretics-resistant edemas is lacking. The objective of this prospective, observational study was to assess the effectiveness and tolerability of combined physiotherapeutic and diuretic therapy in edemas refractory to parenteral diuretics., Methods: A group of 19 patients with advanced disease and severe bilateral leg edema resistant to parenteral diuretic therapy were treated for three days with a combination of multilayer short-stretch compression bandaging and furosemide in hypersaline intravenous infusion., Results: A clinically meaningful decrease in mean limb volume (of 1.52 L; 20.6%; P < 0.0001)-strongly correlating with patients' weight loss (ρ = 0.71; P = 0.0001), with a lowering of the intensity of complaints-was achieved. The treatment was well tolerated, without decreasing the performance status in any patient. Stable levels of blood pressure, laboratory kidney profile (potassium, sodium, creatinine clearance), and serum albumin were observed. Maintenance of the achieved results with a good compliance was seen during an informal follow-up at the hospice., Conclusion: The combination of compression therapy with hypersaline diuretics could be considered as a valuable option for refractory cases of limb edema in advanced disease., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Clitoria ternatea, commonly known as butterfly pea, is a perennial herbaceous plant from the Fabaceae family. It has recently attracted a lot of interest as it has potential applications both in modern medicine and agriculture, and as a source of natural food colorants and antioxidants.Additionally, Clitoria ternateahas been widely used in traditional medicine, particularly as a supplement to enhance cognitive functions and alleviate symptoms of numerous ailments including fever, inflammation, pain, and diabetes.The present study was undertaken to investigate diuretic effect of aqueous and ethanolextracts of the dried flowers of Clitoria ternatea in normal rats.Qualitative analysis of various phytochemical constituents was determined by the well-known test protocol available in the literature.Aqueous and ethanol extracts of Clitoria ternateaflowers were administered to experimental ratsorally at doses of 500 mg/kg p.o. Furosemide (5 mg/kg) was used as positive control instudy. The diuretic effect of the extracts was evaluated by measuring urine volume and sodium content.Phytochemical screening of the extract showed the presence some common compounds like alkaloids, resins, steroids, tannins, saponins, and glycoside.Urine volume was significantly increased by aqueous and ethanol extracts incomparison to control group. While the excretion of sodium was also increased by both extracts.We can conclude that aqueous and ethanol extracts of Clitoria ternateaproduced notablediuretic effect which appeared to be comparable to that produced by the reference diuretic Furosemide. Thepresent study provides a quantitative basis for explaining the folkloric use of Clitoria ternateaas a diuretic agent. [ABSTRACT FROM AUTHOR]

The aim of the current study was to analyze the polyphenols and determines the antioxidant, analgesic and diuretic properties of the methanolic extract of C.speciosus rhizome. DPPH and ferric reducing antioxidant power (FRAP) assays were used to determine the antioxidant activity. Acetic acid-induced writhing and formalin-induced licking experiments were used to assess the analgesic effect. The total phenolic, flavonoid and flavonol contents were found 51.73± 0.25 mg GAE/g dry weight, 3.41± 0.07mg QE/g dry weights and 44.19± 2.24 mg QE/g dry weight, respectively. The plant extract exhibited weak antioxidant activity in the DPPH and FRAP assays, with an IC50 value of 1699±62 µg/mL and an EC50 value of 125±2 µg/mL, respectively. The extract significantly reduced the number of writhes at both doses (200 and 400 mg/kg body weight) as compared to the control. The extract (400 mg/kg) also significantly reduced the percent inhibition of licking by 31.96 and 62.69% compared to the control in the early and late phase, respectively. Compared to the standard drug furosemide, the plant extract also showed a weak diuretic effect. The docking study supported the analgesic activity of rhizome extract. The potent analgesic activity of the plant extract justifies the traditional and medicinal aspects. [ABSTRACT FROM AUTHOR]

The aim of our experimental work was to formulate furosemide-containing rectal suppositories, to study drug release with in vitro membrane diffusion examinations and to increase drug liberation with the use of non-ionic surfactants (Solutol HS 15, Cremophor RH 60, Montanox 60 DF), which were incorporated in the suppository base in various concentrations. Suppocire AS2X proved to be the best suppository base (diffused drug: 69.78%). The use of 1% Cremophor RH 60 additive with the Witepsol H 15 base increased the quantity of the diffused drug from 62 to 75%. The membrane diffusion examinations were followed by studying the influence of suppository bases and additives exerted on the actual diuretic effect in Sprague–Dawley male rats. Once again the Suppocire AS2X suppository base gave the best results compared to the control; the quantity of the animals'' urine showed a fourfold increase. Used with the Witepsol H 15 base, even 1% of all the three additives resulted in a considerable increase of diuretic effect, so their use proved to be advantageous. The comparison of the membrane diffusion examinations with the in vivo diuretic effect reveals that in vitro drug release and the pharmacological effect usually showed the same tendency, that is a greater extent of in vitro furosemide release was associated with a greater quantity of rat urine. [Copyright &y& Elsevier]

The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner. The sweat test was significantly perturbed in those subjects, although the concentration of chloride in sweat did not fall below 60 mEq/l in any of the sweat samples tested. [ABSTRACT FROM AUTHOR]

The bioavailability and diuretic effect of furosemide 40 mg administered orally for at least 6 months have been compared in patients with chronic respiratory failure and in healthy controls. The mean urinary recovery of unchanged drug was 11.5 mg and 9.41 mg in 24 h after pre- and postprandial administration to 10 patients, whereas the recovery was 14.4 mg in 10 healthy subjects. The diuretic effect, in terms of urine flow and sodium ion excretion in the 6 h after administration, was also less in patients than in healthy subjects. This was ascribed to the lower bioavailability of furosemide in patients, based on the urinary recovery of unchanged drug, and not to a lower level of response to furosemide than in healthy subjects. The mean absolute bioavailability of furosemide in 6 patients was 41.3% and 63.4%, respectively, calculated from unchanged drug and total drug (unchanged plus glucuronide conjugate). Approximately 53.9% of the dose of furosemide was excreted as the glucuronide conjugate after oral administration, and 34.2% after i.v. injection in the 6 patients. In 3 of the 6 patients studied, a distinct first-pass effect for glucuronidation of furosemide was observed after oral administration. In another study, the mean glucuronide fraction recovered in 24-h urine was 20.7% and 7.3% ( p<0.01) in 38 patients and 12 healthy subjects, respectively. The fraction in urine was not affected by changing the dose of furosemide from 20 to 120 mg. The lower bioavailability in patients as compared to healthy subjects is ascribed to enhanced glucuronidation and incomplete drug absorption. [ABSTRACT FROM AUTHOR]

The natriuretic effect of the new loop diuretic piretanide was investigated in patients with severe renal insufficiency and was compared with that of furosemide. In the first study 4 hospitalized patients (serum creatinine 407 to 1220 µmol/l) were examined after administration of piretanide (12, 24, 48 and 96 mg to two patients, and 24, 48, 96 and 192 mg to 2 other subjects, given every third day). In the second study 6 hospitalized patients (serum creatinine 194 to 698 µmol/l) were studied after receiving orally 2 different doses of piretanide and 2 different doses of furosemide orally, given every fourth day. The mean natriuretic effect of 48 mg and 96 mg piretanide was 250 and 340% of the control value for the entire group, and 311 to 480% in the subgroup of patients with serum creatinine below 530 µmol/l. For a given dose the natriuresis was inversely correlated with renal function, and at a given serum creatinine level the natriuretic response was dose-dependent. The drug had less effect on water and potassium diuresis than on natriuresis. No significant difference in natriuretic effect was found on comparison with furosemide given in the ratio furosemide: piretanide 3.33:1. The pharmacokinetic data showed a direct correlation between the dose and the mean plasma concentration and also between urinary recovery of the drug and the measured natriuretic response. [ABSTRACT FROM AUTHOR]

To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cl) and the Cl/Cl ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Cl, which was accompanied by an increase in Cl from 57.5±32, and 60.7±27.3 (duplicate measurements) to 103.9±55.4 ( p<0.01) and 103.8±46.5 ml min ( p<0.01). Cl/Cl rose from 0.60±0.24 and 0.61±0.16 to 0.91±0.31 and 0.91±0.21, respectively (both p<0.005). Serum digoxin concentration declined from 1.24±0.35 and 1.19±0.40 to 1.02±0.35 and 0.97±0.32 µg/l (both p<0.01) during the high sodium diet. In the furosemide - induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cl/Cl ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin. [ABSTRACT FROM AUTHOR]

The relative bioavailability and diuretic effect of 2 commercially available tablet preparations of furosemide 40 mg was examined in 10 healthy male volunteers. A close linear relationship between the urinary excretion rate of furosemide and the rate of sodium ion excretion in urine and/or flow rate of urine was demonstrated. There were no significant differences in the urinary excretion of furosemide, sodium and potassium ions or urinary volume following the oral doses. The difference in drug content affected the urinary recovery of furosemide over 24 h but had no effect on the pharmacological response. The analytical power of ANOVA using the various parameters of the responses to furosemide was no lower than when the parameters of urinary excretion of furosemide were used. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of furosemide was studied in 7 patients with diagnosed liver cirrhosis and in 7 healthy subjects. Furosemide in plasma and ascitic fluid was analyzed spectrofluorometrically. After a single intravenous dose, the cirrhotic patients showed lower initial plasma concentrations of furosemide because of the larger volume of distribution. The mean half-life in cirrhotic patients was significantly greater than in healthy volunteers. The longer half-life was associated with a reduction in the serum clearance of furosemide. Ascitic fluid volume in the patients ranged from 4.6 to 7.71. There was no significant amount of furosemide in the fluid. The diuretic interchange between this fluid and plasma was slow, as peak concentrations ranged from 0.3 to 0.5 µg/ml within 3 to 5 h after bolus administration of furosemide. Diuresis and urinary sodium excretion, 5 h after furosemide injection, were similar in both groups; larger potassium excretion was found in the cirrhotic patients. [ABSTRACT FROM AUTHOR]

Furosemide and inulin were given simultaneously by intravenous infusion to nine subjects over 2 h. The concentrations of sodium and of the two drugs in serum (free and protein bound) and in urine were followed during the infusion. In 6 male subjects the investigation was repeated after 3 days of oral treatment with probenecid 500 mg twice daily. Probenecid reduced the average ratio furosemide clearance/inulin clearance from 0.92 to 0.44. In experiments in which no probenecid had been given an average of 2% of the furosemide in urine was excreted by glomerular filtration. In vitro studies showed that the protein binding of furosemide was decreased in the presence of probenecid. The displacing effect of probenecid was confirmed in vivo, and during probenecid treatment glomerular filtration produced an average of 8% of the furosemide excreted by the kidney. The fraction of furosemide excreted by tubular secretion decreased during probenecid treatment from 98.0±0.6% to 91.7±5.6% ( p<0.05). Prior to administration of probenecid, the fraction of the filtered sodium recovered from the urine during furosemide administration was 24.7%. Probenecid reduced that fraction to 21.0% ( p<0.05). The excretion rate of furosemide appeared to be a better predictor of the natriuretic effect than its plasma concentration. Probenecid caused a significant change ( p<0.05) in the regression line relating the log plasma concentration to the natriuretic effect, but it had no effect on the regression line relating the log urinary excretion rate of furosemide to its natriuretic effect. Although the decrease in the furosemide excretion rate during probenecid treatment averaged 25%, the sodium excretion rate was reduced by less than 15%. It is suggested that the natriuretic effect of furosemide is more pronounced if the furosemide molecules enter the tubular lumen at a more proximal level, and it is strongest if they do so by filtration through the glomerulus. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to explore theoretically certain strategies for optimizing the therapeutic index of drugs and to assess these strategies experimentally with two diuretics. Diuretic agents allow dosing rate flexibilities because the temporal profile of diuretic action can vary considerably as long as the total diuretic effect per day is the same. They can also be used in combination. Experiments were designed to determine if the therapeutic index of furosemide and hydrochlorothiazide can be optimized by administering one or the other at a certain rate or by administering the two drugs together in a certain ratio and at a certain rate. Male Lewis rats received one or the other drug, or combinations of the two, by i.v. infusion at different rates. Several timed urine collections were made under steady-state conditions, with excreted urine replaced volume for volume by i.v. lactated Ringer's solution. The urine flow rates and the urinary excretion rates of the diuretics and of Na and K were determined. The relationship between the diuretic effect of either of the two drugs given alone and the respective drug excretion rate could be described by the Hill equation. The ratio of urine flow rate to K excretion rate exhibited a marked dependence on hydrochlorothiazide excretion rate (highest ratio at high excretion rates), whereas the K/Na excretion rate ratio was constant over a wide range of hydrochlorothiazide excretion rates. There was no significant change of these ratios with changing excretion rate of furosemide. Infusion of the two diuretics in combination of different ratios and at different combined rates under steady-state conditions revealed proportionality between the urinary excretion rates of Na and urine over a wide range and a decreasing K /urine excretion rate ratio with increasing urine flow rate. Hence, a favorable increase in the Na/K excretion rate ratio was attained with increasing urine flow rate. These experiments and computer simulations demonstrate in principle the feasibility of optimizing the therapeutic index by appropriate selection of a drug's dosing rate or by dosing a combination of two drugs at an appropriate ratio and rate. [ABSTRACT FROM AUTHOR]

To compare the natriuretic and diuretic effects of a slow-release and a standard formulation of furosemide, 18 elderly patients with stable congestive heart failure were hospitalized and treated with one of these formulations in a double blind randomized trial. Patients received placebo on the first 2 days, furosemide on the third day and placebo again on the last 2 days of the study. In patients receiving the standard formulation mean urine output was increased only on the day of active treatment. However, in patients who had received the slow-release preparation, increased urine excretion was seen both on the day of active treatment and on the subsequent day. The total diuresis (0-48 h) in the 2 groups was equal, but a peak diuresis (0-6 h) was seen only in patients on the standard formulation of furosemide. Sodium excretion followed the pattern of urine excretion. Furosemide in a slow-release formulation offers advantages in maintenance therapy in congestive heart failure, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Furosemide is an orthochtorosuHonamid derivative that is a potent diuretic. This compound marketed by some chemical factories is an agent widely used tor therapy of oedema. This study was made to investigate whether preparations had the description levels of furosemide or not. Furosemide preparations were analyzed by spectrophotometry method. Absorbances were measured at 630 nm. Means of turosemide levels in the tablets and solutions were determinated 39.96±1.89 and 18.62±0.64 mg respectively.