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PubMed1992

[Effects of inhaled and intravenous furosemide on bronchial hyperresponsiveness in patients with chronic congestive heart failure].

We studied the effects of inhaled and intravenous furosemide (40 mg) on bronchial responsiveness to acetylcholine (ACh) in patients with chronic congestive heart failure. The measurement of bronchial responsiveness was performed by inhaling doses of ACh and calculating the provocative concentration of ACh needed to cause a 20% fall in FEV1.0 (PC20-ACh). Intravenous furosemide (N = 11) had a marked diuretic effect (urine output 1014 ml (SEM 156) in 2 hours), but had no effect on resting pulmonary function and PC20-ACh. In contrast, inhaled furosemide (N = 10) had no effect on urine output and resting pulmonary function, but caused significant increase in PC20-ACh from 2.74 (GSEM 1.28) to 8.47 (GSEM 1.22) mg/ml (p less than 0.05). We conclude that inhaled furosemide, but not intravenous furosemide reduces bronchial hyperresponsiveness to ACh in patients with chronic congestive heart failure. The mechanism of this effect appears to be related to the ion transport system of airway epithelium.

Administration, Inhalation↗
PubMed1992

Kinin antagonist blunts the diuretic effect of furosemide in deoxycorticosterone-treated rats.

Furosemide at a dose of 3 mg/kg body wt increased urinary volume (vehicle: 12.8 +/- 0.6; furosemide: 42.4 +/- 2.6 ml/8h, p < 0.01) and urinary sodium excretion (vehicle: 0.9 +/- 0.1; furosemide: 5.0 +/- 0.4 mM/8h, p < 0.01) in deoxycorticosterone-treated rats. These effects were associated to a decrease in mean blood pressure (from 122 +/- 4 to 113 +/- 3 mmHg, p < 0.01) and renal vascular resistances (from 15.6 +/- 0.6 to 14.3 +/- 0.7 RU, p < 0.05). The B2-receptor antagonist D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin significantly blunted the diuretic and natriuretic effect of furosemide and completely prevented the decrease in blood pressure and renal vascular resistances. The renal kallikrein-kinin system may modulate the diuretic and hemodynamic effects of furosemide in conditions of increased mineralcorticoid activity.

Animals↗
PubMed1977

The effect of furosemide on the flow and composition of bile in the dog.

The effect of furosemide, a potent inhibitor of active sodium transport, on the amount and composition of bile was studied in the dog. Ten milligrams per kilogram of body weight of furosemide were injected intravenously to anesthetized dogs with a previously constructed fistula of the common bile duct. In all dogs, a 2.5 times increase in bile flow was observed concomitant with a 15 times increase in urinary output. The amount of bile flow decreased gradually and returned to control levels 60 to 75 minutes after furosemide injection. The choleretic effect was associated with a high increase in sodium, chloride and bicarbonate anions and with a smaller increase in potassium, phosphorus and calcium. The total amount of bilirubin alkaline phosphatase and cholesterol was not significantly affected, while the calculated output of inorganic salts increased. The results indicate that inhibition of sodium reabsorption by furosemide simultaneously affects the liver and kidney and that the increase in electrolyte solution is most likely caused by the inhibition of sodium reabsorption in the ductuli. Furosemide also may interfere with the sodium mediated secretory fraction at the canalicular level, but the predominant factor determining the increase in bile flow and electrolytes is inhibition of sodium reabsorption in the biliary ducts and ductuli.

Alkaline Phosphatase↗
PubMed2006

[Acute generalized exanthematous pustulosis (AGEP) following intake of furosemide].

INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is an acute pustular eruption with unique clinical features, a rapid clinical course and a typical histopathology. The causative agents are mostly drugs but other triggers have also been described. CASE REPORT: A 52 year-old woman with a history of diabetes mellitus type II, dyslipidemia and osteomyelitis was treated for about a year with metformin (Glucophage) and simvastatin (Simovil) tablets. Due to the osteomyelitis, the patient was started on a regimen of intravenous vancomycin as well as furosemide tablets (Fusid) for pedal edema. About seventeen days after beginning treatment with vancomycin and a week after starting furosemide the patient was hospitalized due to an acute pruritic pustular eruption, involving most of her body surface area. Both vancomycin and furosemide treatment were discontinued, and topical treatment was provided. The clinical course was rapid with spontaneous resolution of the pustules followed by a characteristic pin-point post-pustular desquamation. The morphological, clinical and histological findings suggested a definite case of AGEP based on the EuroSCAR scoring system. The latent period between the initiation of medication intake and the appearance of AGEP, as well as a literature search, suggest that furosemide might be the incriminated drug. CONCLUSION: We have described a rare case of typical AGEP most probably induced by furosemide.

Diabetes Mellitus, Type 2↗
PubMed1991

Evaluation of insulin-induced changes in the renal response to furosemide in normal subjects.

Over the last years, a large mass of information has accumulated indicating that changes in the serum insulin concentration can affect renal electrolyte excretion. We analyzed the response of the kidney to furosemide in 5 healthy men, in the presence of both normal physiological serum insulin levels and levels at the upper limit of the physiological range, obtained by the hyperinsulinemic-euglycemic clamp technique. After furosemide administration, glomerular filtration rate, urine flow, urine sodium excretion, free water clearance, urine pH, plasma renin activity and plasma aldosterone exhibited the same behavior in the presence of both serum insulin concentrations. The rise in urinary potassium excretion following furosemide administration was significantly lower in the presence of high insulin concentrations. Although we observed a slight decrease in plasma potassium levels during the equilibration phase of the clamp required before the administration of furosemide, a significantly lower increase in potassium fractional excretion indicated a direct tubular effect of insulin. Thus, in conditions in which natriuresis is mildly stimulated, as in the case of the administration of low doses of furosemide, insulin does not affect the rate of renal sodium reabsorption. Conversely, the hormone has an appreciable influence on the modulation of tubular potassium exchanges.

Adult↗
PubMed1991

Compatibility of cefoperazone sodium and furosemide in 5% dextrose injection.

The compatibility of cefoperazone sodium and furosemide in 5% dextrose injection stored at two temperatures was studied. Cefoperazone sodium and furosemide were added to 5% dextrose injection to achieve a cefoperazone concentration of 10 mg/mL and a furosemide concentration of 0.2 mg/mL. The admixture was stored in 100-mL vented i.v. containers in the dark under refrigeration (4 degrees C) and at room temperature (25 degrees C); three containers were stored at each temperature. A 1-mL sample was taken from each i.v. container immediately after preparation and after 1, 2, 5, 10, 15, 20, and 25 days to be inspected visually, checked for pH value, and analyzed by a stability-indicating high-performance liquid chromatographic method. No color change or precipitation was observed in any sample at any time during the study. More than 95% of the initial concentrations of both drugs remained for five days at 4 degrees C but for only two days at 25 degrees C. Cefoperazone sodium was somewhat more stable than furosemide under the same storage conditions for 25 days; however, less than a 2% difference between the drugs was noted. Under the conditions of this study, cefoperazone sodium 10 mg/mL and furosemide 0.2 mg/mL in admixtures in 5% dextrose injection are stable for only two days at 25 degrees C and five days at 4 degrees C.

Cefoperazone↗
PubMed1990

Effects of furosemide on blood pressure in anephric rats.

This study has been performed in order to evaluate whether furosemide can induce changes in blood pressure independently of its diuretic effects,and whether its pressor effects are connected with the ability to synthetize renal prostaglandins. The experiments were performed in four groups of volume-expanded rats: the first (n.5) had bilateral ligation of the renal vessels; the second (n.8) had bilateral ligation of the ureters; the third group (n.6) had ureters ligation after pre-treatment with indomethacin; the fourth group (n.2) received a pre-treatment with captopril. After blood pressure stabilization, furosemide was administered i.v. (0.125 mg/100 g. of body weight). Indirect readings of the blood pressure were obtained at 1, 2, 3, 4, 5, 7.5, 10, 15, 20 min. After furosemide administration, blood pressure fell down quickly in the rats with ureteral ligation and in those with captopril pretreatment, while the tensive response to furosemide was blunted by the indomethacin treatment. In conclusion, furosemide can reduce blood pressure by a mechanism non related with its diuretic properties, which, however, requires the integrity of the renal connections with the circulatory system.

Animals↗
PubMed1990

Furosemide effect on mineral status of parenterally nourished premature neonates with chronic lung disease.

In this study, the effect of prolonged furosemide administration on calcium and phosphorus homeostasis was examined in 16 parenterally nourished very low birth weight infants with chronic lung disease. Patients received one of three different dosages of phosphorus: low, 0.91 +/- 0.06 mmol/kg per day; moderate, 1.24 +/- 0.02 mmol/kg per day; and high, 1.64 +/- 0.06 mmol/kg per day. All furosemide-treated patients had high levels of urinary calcium (12.1 +/- 2.2 mg/kg per day), phosphate (19.1 +/- 2.7 mg/kg per day), and cyclic 3'5'-adenosine monophosphate (76.8 +/- 6.7 nmol/kg per day) excretion, independent of their phosphorus intake. Parathyroid hormone concentrations were high in furosemide-treated patients (0.95 +/- 0.15 ng/mL) compared with patients not treated with furosemide and receiving either moderate (0.49 +/- 0.05 ng/mL) or low (0.42 +/- 0.07 ng/mL) phosphorus intakes. Furosemide administration may lead to secondary hyperparathyroidism.

Adenosine Monophosphate↗
PubMed1990

Daily administration of furosemide in dilated cardiomyopathy--yes or no?

Seventeen patients with dilated cardiomyopathy (mean ejection fraction 22%) in the NYHA state III or IV were investigated. All patients fulfilled the criteria of an indication for administration of furosemide, since left ventricular filling pressure (LVFP, measured as pulmonary capillary pressure) was 20 or more mm Hg in all. This study investigates the effects of an acute (40 mg i.v.) administration of furosemide (observation period 0 to 90 minutes after administration). Conventional M-mode, 2-dimensional and Doppler-echocardiography was performed in all patients. Patients were divided into 2 groups according to the degree of (relative) mitral regurgitation (MR): group 1 with moderate to severe (n = 10) and group 2 with mild or no MR (n = 7), 90 minutes after administration of furosemide LVFP decreased by 76%. In group 1 this occurred together with a 23% rise of cardiac index and a fall of systemic vascular resistance of 21%. In group 2 cardiac index decreased by 22% with a rise of systemic vascular resistance of 14%. The chronic oral administration of furosemide over 4 weeks ameliorated the NYHA state of all patients by one grade. We conclude from our results that patients with advanced dilated cardiomyopathy profit only from acute administration of furosemide if a significant (relative) MR is present also. A low dose chronic oral administration of the drug, however, leads in any case to clinical amelioration.

Adult↗
PubMed1990

[Pharmacokinetics and pharmacodynamics of furosemide in liver cirrhosis].

12 patients with cirrhosis of the liver (6 with ascites) and 6 control persons were given 80 mg furosemide intravenously and were followed up for pharmacokinetic, renal and haemodynamic effects. The patients with ascitic cirrhosis (AC) and the control persons were found to have the same plasma furosemide concentrations; however, the AC patients excreted significantly less furosemide into the urine in an 8-hour period than the control persons, which was due especially to lower urine furosemide excretion during the first hour after application in comparison with the control group (75 +/- 6.8 vs. 100.8 +/- 8.8 mumol/h, p less than 0.05). During the first post-furosemide hour, the AC patients had a significantly lower diuresis (13.3 +/- 2.4 vs. 23.9 +/- 1.1 ml/min, p less than 0.01) as well as natriuresis (1367.4 +/- 771.4 vs. 3242 +/- 137.5 mumol/min, p less than 0.01) than the control group and a significantly lower excretion fraction of sodium than the patients with live cirrhosis without ascites (6.5 +/- 0.8 vs. 10.7 +/- 1.5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide↗
PubMedDate not supplied

[Effect of furosemide on the plasma level of atrial natriuretic peptide (ANP) in healthy persons and in patients with uncomplicated primary arterial hypertension].

The study included 15 healthy individuals aged 37.3 +/- 7.7 years and 27 patients with the primary uncomplicated blood hypertension (stages I and II according to WHO classification) of the comparable age, untreated and given a diet containing 100-120 nM Na+ daily. Plasma ANP concentrations were measured prior to and after 30, 60, and 90 minutes following 40 mg furosemide intravenously. An increase in 1-minute urine output and 1-minute Na+ excretion in the urine were determined during 90 minutes following furosemide administration. A significant decrease in ANP plasma levels was noted in all examined individuals following furosemide administration in all time intervals comparing with baseline values. An increase in 1-minute urine output and 1-minute sodium excretion with the urine significantly correlated with plasma ANP decrease during 90 minutes following furosemide administration. The obtained results suggest that furosemide inhibits ANP secretion in the patients with uncomplicated primary hypertension similarly to healthy individuals.

Adult↗
PubMed1989

Additive diuretic effect of S-8666 during furosemide-induced diuresis in rats.

In order to verify that the novel uricosuric loop-acting diuretic S-8666 has an additional site of action in the distal tubule, we investigated the additive diuretic effect of S-8666 during furosemide-induced diuresis in rats. Intravenous bolus injection of S-8666 (3-30 mg/kg) and trichlormethiazide (TCM) (1-10 mg/kg) caused dose-dependent increases in Na+ excretion during furosemide-induced diuresis (primary, 10 mg/kg i.v.; sustaining, 10 mg/kg/hr i.v.), whereas injection of furosemide (5 mg/kg) did not. Ca++ excretion was decreased by injection of each drug. A significant reduction in Ca++/Na+ was observed at all doses of S-8666 and TCM. Additional natriuretic and hypocalciuric effects were lower in the S-8666 than in the TCM group. From these observations we conclude that: 1) S-8666 has a natriuretic effect which is additive to that of furosemide; 2) S-8666 attenuates the calciuric effect of furosemide; and, 3) S-8666 may have an additional site of action in the distal tubule.

Animals↗
PubMed1989

Furosemide-sensitive Cl transport in bovine retinal pigment epithelium.

Bovine retinal pigment epithelium (RPE)-choroid explants were sealed in an Ussing chamber. Typical preparations produced a transepithelial voltage (Ve) of 12 mV (retina side positive) and had an electrical resistance (R) of 300 ohm-cm2. These values can be attributed to the RPE. Furosemide and ouabain reduced the Ve without affecting R when applied to the apical side of the RPE, but had no effect upon Ve and R when applied to the choroidal side. Acetazolamide had no effect upon Ve and R when applied to either side of the tissue. In Cl-free medium, ouabain reduced Ve without affecting R, while furosemide had no effect upon Ve and R. In Na-free medium, ouabain and furosemide had no effect upon Ve and R. Unidirectional isotope flux studies performed under open circuit conditions showed a net retina-to-choroid Cl flux that was abolished by furosemide. These results indicate that bovine RPE possesses a furosemide-sensitive Cl transport system.

Animals↗
PubMedDate not supplied

Furosemide 1-O-acyl glucuronide. In vitro biosynthesis and pH-dependent isomerization to beta-glucuronidase-resistant forms.

A biosynthetic acyl-type glucuronic acid conjugate of furosemide was isolated from in vitro incubation of pregnenolone-16 alpha-carbonitrile-induced rat liver microsomes containing UDP-glucuronyltransferase activity, furosemide, and UDP-glucuronic acid. Furosemide 1-O-acyl glucuronide (FG) was specifically hydrolyzed by beta-glucuronidase (BG) and was also labile to alkaline hydrolysis. FG concentration decreased at an apparent first order rate when incubated at 37 degrees C in buffer solution of pH values greater than 6.0 with only moderate hydrolysis of the conjugate at pH values less than 8.5. Formation of rearrangement forms of FG that were resistant to BG but labile to alkaline hydrolysis accounted for most of the disappearance of FG at this pH range. Radiochemical labeling of the conjugate with either 14C-furosemide or 14C-UDP-glucuronic acid was detected in the BG-resistant isomerization products of FG as they were separated by HPLC. The structure of FG and its isomerization products was further verified by negative ion thermospray liquid chromatography/mass spectrometry. The abundant (M - 1)-ion at mass 505, the aglycone fragment at m/z 329, and the characteristic sugar fragment ion of mass 175 were found in the spectra of FG and three additional isomers. An ion at m/z 221 was noted only in the case of the parent conjugate and thus may prove to be a characteristic ion for 1-O-acyl-linked glucuronides under negative ion thermospray. In vivo as well as in vitro rearrangement of FG to BG-resistant forms might affect the results of furosemide disposition studies which use BG hydrolysis to determine FG formation.

Animals↗
PubMed1986

Post-prostatectomy auto-irrigation with furosemide in the tropics.

A progressive study was carried out in 49 patients who underwent prostatectomy (10 transurethrally and 39 transvesically) to assess the effects of furosemide given intravenously for post-operative bladder irrigation. All 10 transurethral patients and 17 of the transvesical patients received furosemide, the remaining 22 patients receiving formal external bladder irrigation with saline. The results showed that post-operative infection was lowest and bed stay shortest in the patients with furosemide auto-irrigation. There was also less need for blood transfusion. No significant changes in haemoglobin and packed cell volume were observed in the transurethral patients; however, both decreased significantly in all 39 patients with transvesical prostatectomy, whether or not furosemide was used. Auto-irrigation with furosemide was found to be associated with a significant post-operative decrease in serum potassium but not in serum sodium levels. When external irrigation with saline was used, there was a significant increase in serum sodium.

Aged↗
PubMed1986

The influence of furosemide on intrarenal distribution of 2-sulphanilamido-5-methoxypyrimidine in rats with normal and reduced renal parenchyma.

Internal distribution of 2-sulphanilamido-5-methoxypyrimidine (SM) 100 mg/kg in rats is characterized by a corticopapillary gradient. The papilla/cortex ratio of SM concentration averaged 2.25 +/- 0.34. Furosemide (5 mg/kg) elicited a significant corticopapillary gradient decrease for SM. Corticopapillary gradients for SM and sodium showed a positive correlation (r = 0.45; p less than 0.001). After furosemide corticopapillary gradient for SM averaged 1.4 +/- 0.22. Unilateral nephrectomy alone induced no significant difference in the corticopapillary gradient for SM compared with controls. Corticopapillary gradient for SM was significantly lower in unilaterally nephrectomized rats than in controls when furosemide was given after 24 hours or 7 or 14 days. The results suggest that SM concentration was significantly higher in the medulla than in the cortex; furosemide led to a significant decrease of corticopapillary gradient for SM against controls; the corticopapillary gradient for SM did not significantly change after unilateral nephrectomy; the effect of furosemide on corticopapillary gradient for SM was more pronounced in rats after unilateral nephrectomy than in controls.

Animals↗
PubMed1988

Comparison of diuretic effects and pharmacokinetics of torasemide and furosemide after a single oral dose in patients with hydropically decompensated cirrhosis of the liver.

In a controlled double-blind randomized clinical trial, the pharmacodynamics and pharmacokinetics of 20 mg torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) (n = 10) and 40 mg furosemide (n = 9) were compared over 24 h after single oral administration to patients with ascites due to cirrhosis of the liver. The overall 24-h excretion of volume and sodium was not significantly different between patients receiving torasemide or furosemide. The diuretic effect of torasemide, however, was longer in duration than that of furosemide. This was in accordance with the pharmacokinetic behaviour of torasemide and furosemide. The serum elimination half-life of torasemide was longer (4.8 h) than that of furosemide (2.2 h) in these patients and also longer than that in healthy volunteers (3 h). The areas under the serum concentration-time curves for torasemide were higher than in healthy subjects by a factor of 2.5. In parallel with the considerably delayed formation of the diuretically inactive metabolite M5, which is formed via the diuretically active metabolite M1, the serum concentration of M1 was increased in these patients. However, the overall excretion of torasemide and the different metabolites was similar compared to healthy volunteers. These results indicate that the pharmacokinetics and metabolism of torasemide depend on liver function. No adverse reaction were experienced in either group.

Administration, Oral↗
PubMedDate not supplied

[Determination of the specific activity and biological availability of Soviet-made furosemide].

Experiments on mice, rats and dogs showed that furosemide manufactured in the USSR is not inferior by its specific activity to furosemide manufactured abroad. Furosemide manufactured in the USSR and furosemide-substance made in Finland were compared at three doses--1, 5 and 25 mg/kg. The bioavailability of furosemide tablets manufactured in the USSR and that of "Polfa" production tablets studied on rats (5 and 25 mg/kg) and dogs (40 mg) appeared to be identical.

Animals↗