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PubMed1996

Importance of sonography with furosemide in continuing dilatation after pyeloplasty.

The continuance of collecting system dilatation after plastic repairing of the ureteropelvic junction in children progressed hydronefrosis may have two causes, the first one is a great progress of the process, that do not allow to repair the dilatation, the second one is to be a failure with the operation. Another treatment depends on differentiating there two causes. Authors used ultrasonography with furosemide test. By comparing sonogram before and after giving furosemide. They described whether the continuance of collecting system dilatation can be caused by a urodynamic obstruct. The result is that the ultrasonography with furosemide is a simple of orientation noninvasive method, which can be used several times without risks for the children. According to experience of the authors more precise is the method with oral furosemide application that the intravenous. It is a method of orientation which can be filled by dynamic scintigraphy in case of suspicion on bad evacuation with furosemide. Then if the obstruction is confirmed, we can indicate the excretory urography with furosemide.

Administration, Oral↗
PubMed1998

No influence of furosemide on human erythrocyte shape and volume and blood viscosity in vitro.

Furosemide is a diuretic agent which is often given in high concentration intravenously. Since erythrocytes have a furosemide-sensitive transport system and oral application of furosemide was found to induce an echinocytic shape transformation in horses, we have analysed the influence of furosemide on erythrocyte shape, volume and blood viscosity in vitro. Increasing plasma furosemide concentrations of 0, 1, 10, 100 and 1000 micrograms/ml did not affect the erythrocyte volume or shape and left blood viscosity unaffected. We conclude that furosemide has no influence on blood rheology in humans.

Administration, Oral↗
PubMedDate not supplied

[The pharmacodynamics and pharmacokinetics of furosemide during ordinary life activities and during head-down tilt hypokinesia in a healthy subject].

The object of the work was comparative study of the characteristics of pharmacodynamics and pharmacokinetics of the diuretic furosemide during ordinary vital activity of man and under conditions of antiorthostatic hypokinesia. Six practically healthy males were examined. They took part successively in two experimental series: series 1--during an ordinary motor regimen under ambulatory conditions; series 2--under conditions of antiorthostatic hypotension (ANOH, 12 degrees). In both series with absolute correspondence of the procedures and order of manipulations the subjects were given 40 mg furosemide per os, venous blood and urine were repeatedly tested, and the physiological data were recorded. In combined action of an antiorthostatic position of the body and the diuretic an additive effect was encountered, i.e., increased therapeutic effect of, furosemide. The blood serum electrolyte composition practically did not change in this case. After oral administration of 40 mg furosemide maximal concentration of the drug in the blood (977 +/- 151 ng/ml) was found on the average in a group in 1.3 +/- 0.2 h. The drug half-life period in this case was 1.1 +/- 0.4 h; total clearance was 24.7 +/- 2.8 liter/h, and the distribution volume was 33.7 +/- 12.7 liters. In maintenance of antiorthostasis furosemide pharmacodynamics and pharmacokinetics changed but the individual character of the dynamics of drug concentration in the blood persisted. No statistically significant differences in the mean group pharmacokinetic parameters of the drug during an ordinary motor regimen and in antiorthostatic hypokinesia were encountered. Furosemide given in antiorthostatic hypokinesia led to diminished filling of the upper and middle parts of the lungs with blood despite the attendant decrease in the tonus of the resistant vessels.

Adult↗
PubMed1998

[The effect of furosemide on urinary excretion of oxalic acid, vitamin C and vitamin B6 in chronic kidney failure].

The authors describe the effect of a single i.v. dose of 20 mg furosemide on the excretion of oxalic acid, vitamin C and vitamin B6 in a control group and in patients with chronic renal failure without dialyzation treatment. An increased urinary excretion of oxalic acid, vitamin C and vitamin B6 was found during the first three hours after furosemide administration in both groups. The effect of furosemide persisted for six hours in patients with chronic renal failure without dialyzation treatment. The authors described a new hitherto unknown positive side-effect of furosemide, i.e. enhanced urinary oxalic acid excretion in the control group and in patients with chronic renal failure without dialyzation treatment and a negative side-effect of furosemide, i.e. increased urinary vitamin B6 excretion in both examined groups. With regard to the assembled results the authors recommend in addition to monitoring of vitamin C also monitoring of vitamin B6 in plasma during long-term administration of large doses of furosemide to patients with chronic renal failure as deficiency of these vitamins could develop.

Adult↗
PubMed1998

Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.

In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.

Adult↗
PubMed1999

Differential effect of the loop diuretic furosemide on short latency auditory and vestibular-evoked potentials.

OBJECTIVE: This study aimed to investigate the differential effect of the loop diuretic furosemide on the auditory and vestibular (otolith) end organs in the same animals simultaneously. DESIGN AND METHODS: Auditory nerve-brain stem-evoked responses (ABR-generated in the cochlea) and short latency vestibular-evoked responses to linear acceleration impulses (L-VsEP-generated in the otolith organs) were recorded from albino Sabra rats both before and at minute intervals after intravenous injections of the loop diuretic furosemide. In some animals, an equal volume of saline was injected to control for the effect of the injection itself. In most animals, more than one injection of saline or furosemide was possible (furosemide, N = 17 injections in 10 rats; saline, N = 18 injections in 9 rats). Peak-to-peak amplitude and peak latency changes in the first wave in each recording (representing end-organ activity) as a function of postinjection time were compared between the two evoked potentials using analysis of variance and repeated t-tests. RESULTS: Saline injections caused only minor changes in the amplitude of the ABR and the L-VsEP. After administration of furosemide, the amplitude of the L-VsEP hardly changed. However, there was a noticeable decrease in the amplitude of the ABR. CONCLUSIONS: Although furosemide has a major depressant effect on cochlear function, vestibular end-organ activity is hardly altered.

Analysis of Variance↗
PubMed1993

Furosemide ototoxicity is enhanced in analbuminemic rats.

OBJECTIVE: The purpose of this study was to investigate the effect of furosemide on the endocochlear potential (EP) of Sprague-Dawley rats and rats that lack albumin in their serum (Nagase analbuminemic rats [NAR]). DESIGN: Group comparisons between analbuminemic rats and normal Sprague-Dawley rats was carried out, with statistical evaluation using the Student's t test. SETTING: Experiments were carried out in a sound-attenuated booth in a research laboratory. SUBJECTS: Young adult Sprague-Dawley and analbuminemic rats (NAR) 50 to 80 days of age were used as experimental animals. INTERVENTIONS: Subjects were anesthetized with ketamine and xylazine. Furosemide, 35 mg/kg, was injected intravenously in each of three groups: NAR rats, NAR rats pretreated with albumin and normal Sprague-Dawley rats. MAIN OUTCOME MEASURES: Endocochlear potential was measured via the round window membrane approach. Urine samples were collected with a metabolic cage, and volumes were recorded. RESULTS: Sprague-Dawley rats had a very slight EP reduction following furosemide. The NAR rats, however, were found to have an extremely large and rapid reduction of the EP one order of magnitude greater. The NAR rats pretreated with albumin had a significantly smaller reduction of EP than NAR rats not receiving albumin. However, NAR rats pretreated with albumin had a significantly greater urine output than control NAR rats. CONCLUSIONS: These findings support the hypothesis that the access of furosemide to its site of ototoxic action in the cochlea depends on the quantity of unbound furosemide in the serum.

Action Potentials↗
PubMed1981

Furosemide use in premature infants and appearance of patent ductus arteriosus.

Furosemide is a known stimulant of the renal release of prostaglandin E2, a potent dilator of the ductus arteriosus. A possible relationship between furosemide use in infants with respiratory distress syndrome (RDS) and the incidence of patent ductus arteriosus (PDA) was investigated using two different retrospective analyses. The amount of furosemide administered prior to the day a murmur was heard in the infants with PDA was higher than the amount given to patients without PDA during the same period. In a historical analysis of patients treated for RDS in the years 1970 through 1979, furosemide use and fluid intake appeared to be independent factors contributing to the incidence of PDA. The proposed relationship between furosemide use and the occurrence of PDA in patients with RDS warrants further study.

Ductus Arteriosus↗
PubMed1989

Alternating sequential dosing with furosemide and ethacrynic acid in drug tolerance in the newborn.

Drug tolerance seems to develop rapidly after the administration of sequential doses of the same loop diuretic. We evaluated whether alternating different loop diuretics could achieve the same initial diuretic response in the newborn. In a randomized double crossover study, we examined the diuretic and saliuretic effects of alternating doses of furosemide and ethacrynic acid (1 mg/kg administered intravenously every 24 hours) in 10 newborns, who received the drugs in the following sequential order: (1) furosemide, (2) ethacrynic acid, and (3) furosemide (group 1, n = 5); and (1) ethacrynic acid (2) furosemide, and (3) ethacrynic acid (group 2, n = 5). Hourly urine specimens were collected for the determination of rates of urinary and fractional excretion of sodium, chloride, and potassium and of urinary flow, before and 6 hours after dosing. There were no differences between the groups at each dose for all parameters measured. A significant decrease in prediuretic and postdiuretic rates of urinary flow, in sodium and chloride excretion, and in the fractional excretion of these electrolytes was observed before and after dosing. The associated reduction in patients' weights suggested a depletion in plasma volume. In conclusion, consecutive alternation of furosemide and ethacrynic acid in the same newborn does not prevent the development of pharmacologic tolerance to loop diuretics, since diuresis, natriuresis, and chloriuresis decrease after successive sequential administration of these drugs.

Creatinine↗
PubMedDate not supplied

Dose-dependent pharmacokinetics of furosemide in the rat.

The pharmacokinetics of furosemide were investigated in the rat at doses of 10 and 40 mg kg-1 corresponding to doses of 80 and 320 mg given to humans based on body surface area. A three-compartment open model with renal excretion taking place from the shallow peripheral compartment gave the best fit to the data. The terminal half-life of furosemide was found to change from 29 min for the 10 mg kg-1 dose to 49 min for the 40 mg kg-1 dose. This change could be detected as a change in the apparent volume of distribution caused by decreased protein binding at increasing plasma concentrations of furosemide. The total plasma clearance did not change significantly although metabolic and renal clearance both changed. The renal clearance was found to be dependent on the free fraction of furosemide in plasma and thus increased with increasing plasma concentrations. The metabolic clearance decreased with increasing dose indicating a saturable metabolism of furosemide.

Animals↗
PubMed1976

Effect of furosemide on the renal excretion of digoxin.

Digoxin serum and urine levels were determined by radioimmunoassay in 6 subjects (4 patients with heart disease and 2 volunteers without heart disease) who had been maintained on oral digoxin (0.25 or 0.5 mg daily). Observations were made during a 3-day control period and then during 8 days of concomitant digoxin and oral furosemide (40 mg daily) therapy. Serum digoxin levels determined 10 and 24 hr after each dose of digoxin averaged 1.2+/-0.1 ng/ml (M+/-SE) during control and 1.3+/-0.1 during the last 3 days on digoxin and furosemide. The daily urinary excretion of digoxine averaged 51+/-6% of the oral dose during control and 52+/-6 during the entire period of furosemide administration. The renal clearance of digoxin and creatinine averaged 94+/-7 and 87+/-11 ml/min, respectively, during control; corresponding values were 88+/-8 and 85+/-9 for urine collections demonstrating a distinct diuretic effect of furosemide and 87+/-8 and 75+/-10 for urine collections not demonstrating such an effect during diuretic therapy. The results suggest that the diuretic effect of furosemide does not significantly affect the excretion of digoxin

Adult↗
PubMed1977

Depression of renal clearance of furosemide in man by azotemia.

The renal clearance of furosemide and tetraethylammonium (TEA) were compared in 10 patients with hypertensive nephropathy. BUN and creatinine ranges were 10 to 88 mg/dl and 0.9 to 3.8 mg/dl, respectively. Diuretics were discontinued 48 hr prior to the study, and 2 consecutive clearances (ml/min/1.73 m2BSA) of creatinine were performed. The patient then received a bolus followed by a constant infusion of furosemide-14C and tetraethylammonium-14C (analyzed by specific methodology for plasma and urine), both in subpharmacologic doses. After 40-min equilibration sequential 20-min clearance periods were obtained. Both the clearance of furosemide (range 17 to 133) and TEA (range 99 to 443) correlated negatively with BUN and serum creatinine and positively with creatinine and urea clearances. Thus, by using a constant-infusion technique we demonstrated that the renal clearance of furosemide is depressed by azotemia in man and that there was greater depression with furosemide than with TEA.

Adult↗
PubMed1977

Elimination of furosemide in healthy subjects and in those with renal failure.

Furosemide was administered intravenously to 5 healthy volunteers and 15 patients with various degrees of renal failure. Two patients were given the drug orally. The plasma half-life of furosemide averaged 0.79 hr in the healthy subjects. Although most patients with kidney disease had a prolonged half-life (t1/2), up to 24.58 hr, some with advanced renal failure had an almost normal t1/2. The plasma clearance of furosemide, which in the normal subjects averaged 194 ml/min, decreased proportionally with decreasing creatinine clearance, as did the renal clearance, which in the healthy subjects averaged 95 ml/min. There was no correlation between kidney function and the apparent volume of distribution or of nonrenal clearance. One patient was given 35S-labeled furosemide intravenously. Although the furosemide plasma t1/2 was essentially normal, the elimination rate of metabolites was decreased. Unlike that of healthy subjects, the main route of excretion of label was in the feces.

Administration, Oral↗
PubMed1978

Furosemide kinetics in renal failure.

Furosemide kinetics were studied in normal volunteers and patients with renal failure. Comparison of results from intravenous bolus and intravenous infusion in normal subjects showed no significant model dependency of estimations of furosemide clearance, although the average clearance by fitting to a one-compartment model was 16% higher than that obtained by fitting to a two-compartment model. Normal subjects had a total body clearance of furosemide of 1.53 +/- 0.11 (SE) ml/min/kg, a volume of the central compartment of 2.61 +/- 0.37 L, a volume of the peripheral compartment of 2.48 +/- 0.24 L, and a half-life of 0.8 +/- 0.06 hr and they absorbed 68.9% +/- 7.1% of a solution of furosemide given by mouth. The corresponding values in patients with renal failure were 0.27 +/- 0.03 ml/min/kg, 8.02 +/- 0.96 L, 14.1 +/- 3.57 L, 14.2 +/- 2.30 hr, and 43.4% +/- 8.0%, all differing significantly different from the normal. The bioavailability of 500-mg tablets of furosemide in the renal failure patients was 43.4% +/- 7.4%, equivalent to the absorption of the dose given to the same patients in the form of a solution.

Administration, Oral↗
PubMed1979

Effect of furosemide on serum clearance and renal excretion of digoxin.

Serum turnover and urinary excretion of digoxin with or without oral furosemide were studied in six healthy subjects who received 0.006 mg/kg body weight digoxin intravenously. During furosemide treatment, the total amount of urinary digoxin did not change but the digoxin clearance during the diuretic phase and the digoxin excretion after the diuresis decreased significantly. The average serum half-life was prolonged from 37 hours in the control period to 86 hours in the furosemide period. Decreased glomerular filtration rate by volume depletion might have been responsible for the decreased excretion of digoxin, but there was no significant difference in urine volume after diuresis between the two periods, suggesting the possibility of inhibition of tubular secretion of digoxin by furosemide. It is also possible that serum digoxin concentration may be elevated if furosemide were given more frequently.

Adult↗
PubMed1980

Effect of pH, chlorobutanol, cysteine hydrochloride, ethylenediaminetetraacetic acid, propylene glycol, sodium metabisulfite, and sodium sulfite on furosemide stability in aqueous solutions.

A study was conducted to determine the effects of pH, two antioxidants, a chelating agent, a preservative, and propylene glycol on furosemide stability. Aqueous solutions of furosemide containing 10% alcohol (v/v) were prepared in phosphate buffers with various pH values (5, 6, and 9) whose ionic strength was adjusted to 0.1 M with potassium chloride. Some solutions contained chlorobutanol, ethylenediaminetetraacetic acid, or sodium metabisulfite. Another set of aqueous solutions contained phosphate buffer (0.1 M), alcohol (10% v/v), and propylene glycol (40% v/v) with or without cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite. The solutions were divided into two parts, stored at 24 and 50 degrees, and assayed frequently using a previously developed high-pressure liquid chromatographic procedure. At the lowest pH value (pH 5), furosemide appeared to be very unstable. Cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite failed to improve the stability of furosemide. Chlorobutanol and sodium metabisulfite had an adverse effect on the stability, probably due to the fact that they decreased the pH of the solution. The pH value appears to be the only critical factor for the stability of furosemide. Buffered solutions containing propylene glycol were very stable at both temperatures for 170 days, and they tasted good.

Chemical Phenomena↗
PubMed1985

Urinary protein binding, kinetics, and dynamics of furosemide in nephrotic patients.

The urinary protein binding, kinetics, and dynamics of furosemide were studied in five nephrotic patients after intravenous dosing. Serial plasma and urine samples containing furosemide were analyzed by HPLC, and drug binding to plasma and urinary proteins was determined using equilibrium dialysis techniques. In comparison to data reported previously in healthy subjects, the steady-state volumes of distribution and nonrenal plasma clearances were significantly increased in nephrotic patients, reflecting the reduced binding of furosemide to plasma proteins. Although there was no significant difference in renal clearance between these two groups, the unbound renal clearance of furosemide was significantly reduced in nephrotic patients even when compensated for by the number of functioning nephrons. Furosemide was extensively bound to urinary protein (19.6-78.4%), and the binding was dependent on the degree of proteinuria. Nevertheless, dose-response analyses, in which the response was represented by sodium excretion rate and the dose by urinary excretion rate of unbound drug, demonstrated that nephrotic patients were less responsive to equivalent amounts of unbound diuretic as compared to healthy subjects.

Adult↗
PubMed1999

Continuous dose furosemide as a therapeutic approach to acute respiratory distress syndrome (ARDS).

BACKGROUND: Acute respiratory distress syndrome (ARDS) is seen in a variety of clinical settings in critically ill patients. ARDS has been defined as a clinical syndrome characterized by progressive hypoxemia, tachypnea, and generalized patchy bilateral pulmonary infiltrates in the absence of cardiac failure. Furosemide has been shown to improve pulmonary gas exchange and intrapulmonary shunt in animal models of ARDS by preferential perfusion of nonedematous lung units. We hypothesized that continuous dose furosemide would improve lung injury during resuscitation from oleic acid-induced lung injury in canines. METHODS: Ten mongrel dogs were anesthetized and given intravenous oleic acid (0.1 mg/kg) to induce lung injury. Once lung injury was established (2 h) the control animals (n = 6) were continued on standard supportive therapy, and the study animals (n = 4) were started on continuous dose furosemide at 0.2 mg/kg/h. Cardiac filling pressures were maintained in all animals by infusion of isotonic saline solution. Data collected included lung injury score (LIS), cardiac index (CI), stroke volume index (SVI), pulmonary capillary wedge pressure (PCWP), urine output (UO), volume of resuscitation (VR), and pulmonary shunt fraction (Qs/Qt). Data were collected at baseline, established lung injury (2 h), and end of protocol (6 h). Data were compared between groups at various stages of the model using one-way analysis of variance with repeated measures. RESULTS: All 10 animals survived the protocol. There was no difference between the experimental and control groups at baseline or established lung injury (2 h) for CI, SVI, PCWP, or VR. There was a significant improvement in PO2/FIO2 and reduction of PEEP values in the furosemide group. There was also a statistically significant difference between experimental and control groups in LIS, Qs/Qt, and urine volumes. CONCLUSIONS: Continuous dose furosemide therapy improves LIS, PO2/FIO2, and Qs/Qt and decreases PEEP requirements in this oleic acid model of ARDS.

Animals↗