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PubMed1998

Treatment of heartwater: potential adverse effects of furosemide administration on certain homeostatic parameters in normal sheep.

Diuretics, in particular furosemide, are generally recommended as a supportive treatment in the advanced stages of heartwater in ruminants. However, after what appeared to be possible adverse effects accompanying its use in field cases of heartwater, the effects of this drug on certain blood and urine parameters were investigated in normal sheep at the same dose rates. Diuresis with concomitant natriuresis was significant after furosemide administration, as was the expected plasma volume decrease. Other significant changes included metabolic alkalosis, hypokalaemia and reduced blood ionised calcium. The difference in duration of the diuretic effect and the duration of the changes in blood parameters from c. 3 h and c. 6 h respectively make it difficult to determine a time interval between successive treatments with furosemide. It appears that the probable cause of death of sheep with heartwater is a drastic reduction in blood volume and decreased cardiac output that leads to general circulatory failure. A therapeutic approach that involves further loss of plasma volume due to diuresis appears contradictory. The added effects of potentiating respiratory alkalosis and the terminal drop in blood ionised calcium seen in heartwater-affected animals indicate that the use of furosemide in supportive treatment of this disease is not warranted.

Alkalosis↗
PubMedDate not supplied

Efficacy of nebulized furosemide in children with moderate attack of asthma.

BACKGROUND: Bronchodilators are the most commonly used drugs for asthma. However, alternative treatment is necessary for those patients who experience adverse effects from bronchodilators. OBJECTIVE: To investigate the efficacy of nebulized furosemide in children with moderate asthma exacerbations. METHOD AND MATERIALS: A double-blind randomized, controlled trial involving three groups of children with moderate attack of asthma. Twenty children were enrolled in group A and received nebulized albuterol, 20 children in group B received nebulized furosemide and 19 children in group C received both albuterol and furosemide. Pulmonary function parameters, peak flow rates, respiratory rate, oxygen saturation and clinical scores were obtained before and after treatment. RESULTS: The maximum increases in FEV1 achieved were 21.1 +/- 4.6 %, 20.8 +/- 3.2 and 21.7 +/- 4.9 in groups A, B and C respectively. The differences between the groups were not significant. Maximum increase in FVC was 20.3 +/- 1.6, 22.5 +/- 5.8 % and 24.5 +/- 4.9 % in groups B and C respectively. The difference between the three groups was not statistically significant. With regards to peak expiratory flow rate (PEFR), the mean increase after treatment was 23.5 +/- 8.6% and 21.8 +/- 6.3% in groups A and B respectively. There was significant increase in PEFR in group C children (26.0 +/- 9.1%; p = 0.01). There was no statistical significant difference among the three groups regarding the improvement in respiratory rate, SaO2 and clinical scores. CONCLUSION: Combination of both furosemide and albuterol led to significant increase in peak flow rate but it did not significantly affect FEV1, FVC, FEF 25-75, respiratory rate, SaO2 or clinical scores as compared to other groups. There were no significant adverse effects from the three drugs used.

Albuterol↗
PubMed1999

Inclusion complexation of furosemide in cyclodextrins. Part 2: Implication on bioavailability.

The effect of inclusion complexation of furosemide in cyclodextrins (CyD) on the bioavailability of the drug was studied on normal human volunteers. The excretion rate of the drug was determined by HPLC for a period of 24 h. post dosing. Several pharmacokinetic parameters were calculated and statistically analyzed. viz., peak excretion rate, peak excretion time, half peak time, elimination rate constant, area under the excretion rate time-curve as well as the total amount of drug excreted. The obtained results show that on administration of furosemide in the form of an inclusion complex in CyDs particularly beta-CyD or its dimethyl derivative may improve its biological performance, taking into consideration that furosemide is characterized by a rapid onset and a short duration of action. Inclusion complexation of furosemide in CyDs leads to a more or less delay in its onset of action, a significant increase in its duration of action as well as significant augmentation in its overall biological availability.

Adult↗
PubMed1975

[Hyperpolarization of frog skin exposed to furosemide].

When applied only to the outer surface of the isolated frog skin furosemide caused a prompt, dose-related (0.1--1.0 mg/ml) and fully reversible increase in potential difference; it did not change the short-circuit current, however. Potential differences were not altered by furosemide in the Ringer-sulphate solution. Furosemide-induced increase of potential differences could be reversed by nystatine which increased the ionic permeability. These results suggest that furosemide could decrease the passive entrance of chlorides through the barrier of the apical cell membrane of the frog skin.

Animals↗
PubMed1975

Separation and quantitative analysis of furosemide and 4-chloro-5-sulfamoylanthranilic adid (CSA) by high pressure liquid chromatography.

After extraction by ether from acidified plasma or urine and concentration into basic phosphate buffer, furosemide and 4-chloro-5-sulfamoylanthranilic acid (CSA) were separated on a high pressure liquid ion-exchange system and measured fluorometrically. Sensitivity is 0.2 mug/ml of ether compound in plasma and 0.1 mug/ml in urine with an 8% coefficient of variation. Interference by porphyrins in urine was eliminated by subtracting a second fluorometric measurement at a different wave-length from that used for furosemide. No quenching at this wave-length is seen with concentrations of furosemide up to 50 mug/ml. Standard curves of furosemide and CSA are linear from 0.2 mug/ml to 50 mug/ml.

Chromatography↗
PubMed2001

The influence of inhaled furosemide on adverse effects of ACE-inhibitors in airways.

BACKGROUND: A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and inflammatory neuropeptides in the airways. MAIN PURPOSE: The aim of this study was to follow the relationship between 15-days administration of enalapril and the defence reflexes of the airways of experimental animals and possibility of pharmacological restriction with inhaled furosemide. METHODS: From the defence reflexes of the airways the changes of the parameters of a mechanically induced cough in nonanaesthetized cats were measured. The reactivity of the smooth muscle of the airways to the bronchoconstrictor mediator was evaluated by in vitro method. The enalapril was administered for 15-days in the dosage of 5 mg/kg b.w. p.o., inhaled furosemide for 15-days in the dosage 10 mg/kg b.w. RESULTS: The results suggested that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to the histamine. The reactivity of the lung smooth muscle was not influenced significantly after enalapril treatment. Inhaled furosemide administered with enalapril significantly decreased the enalapril induced cough and decreased enalapril potentiated reactivity of the tracheal smooth muscle to the histamine. CONCLUSION: The results showed the protective effect of inhaled furosemide against the respiratory adverse effects induced by ACE-inhibitors administration.

Administration, Inhalation↗
PubMed2001

[The furosemide test in diagnosis of the cause of bronchial obstruction].

The authors studied the rate of relief in cases of moderate, reversible airway obstruction after Furosemide administration. They examined 25 patients with bronchial asthma and chronic obstructive bronchitis (mean age 49 years). They found out that intravenous administration of Furosemide to patients with chronic obstructive bronchitis has a significant bronchodilating effect. The reduction of interstitial lung water and the decrease in congestion of airways mucosa in latent left ventricular failure may be the possible explanations of this phenomenon. After administration of Furosemide by inhalation, a mild decrease in airway obstruction was observed in asthmatic patients. The influence of Na+/K+/Cl- transport in the bronchial epithelium, or changes in PGE2 are supposed to represent the effective mechanisms. The authors conclude that Furosemide given intravenously to patients with moderate airflow limitation in connection with lung function tests may be helpful in the diagnosis of the nature of airway obstruction.

Administration, Inhalation↗
PubMed1975

[Activation of the fibrinolytic system by furosemide (author's transl)].

Intravenously administered furosemide induces besides its well known diuretic effect a significant activation of the fibrinolytic system. This fibrinolytic effect, however, is only seen in persons with an intact renal system, not in nephrectomized patients and not in patients with chronic renal insufficiency. From this finding the conclusion is drawn that furosemide needs for its fibrinolytic effect the intact renal tissue. It is discussed that the beneficial therapeutic value of high-dose furosemide in acute renal insufficiency following shock or septic abortion might at least partially be due to furosemide-induced fibrinolysis of the microthrombi of the glomerula.

Abortion, Septic↗
PubMed1976

Renal hemodynamic response to furosemide in septic and injured patients.

Furosemide frequently is advocated as a prophylaxis against renal failure in septic and injured patients; this effect is thought to be secondary to an increase in renal blood flow. This postulate was tested within 72 hours of admission in 22 previously healthy patients with acute pancreatitis (two), massive trauma (ten), or severe sepsis (ten). Renal clearances of inulin (GFR), para-amino hippurate (ERPF), sodium (CNA), osmoles (COsm), and free water (CH2O) were measured in milliliters per minute before and after the intravenous infusion of furosemide (0.5 mg. per kilogram of body weight). Renal vein PAH levels (EPAH) in eight patients were used to calculate true renal plasma flow (TRPF), true renal blood flow (TRBF), and renal vascular resistance (RVR). Furosemide caused a significant increase in urine volume, CNa, and COsm; there were no significant changes in GFR, ERPF, RVR, TRBF, and EPAH. These findings also were observed when the patients were subgrouped according to elevated, normal, or low renal plasma flow and elevated renal vascular resistance. No significant changes were seen in EPAH, thus making a redistribution of renal blood flow unlikely. These studies indicate that furosemide has only a diuretic effect and no hemodynamic effect in the kidney; it has the potential of seriously reducing the circulatory volume and causing renal failure in critical patients.

Acute Disease↗
PubMed1975

[Evoked response audiometry of the guinea pig before and after drop in hearing induced by furosemid (author's transl)].

Using particular surface electrodes evoked response audiometry (ERA) can be applied to small laboratory animals without any sedation or anaesthesia. In addition to other methods we have studied in this way the influence of extreme doses of Furosemid on the guinea pig inner ear. 6-20 mg Furosemid per 100 g of bodyweight (about 100 times the human therapy dose) were applicated i.v. within 5 min resulting in a drop of hearing immediately. For the anaesthesized animal the cochlear microphonic potentials (CM) decrease simultaneously, indicating Furosemid to act at the inner ear itself. By both methods recovery of inner ear function is seen to start about 10 min later according to the little biological half life of Furosemid. As being restricted in respect of time for the CM-measurements we are sure about reversibility only by the ERA-method.

Animals↗
PubMedDate not supplied

[Succinate dehydrogenase and Na+-K+-ATPase activities in cells of rat kidney tubules during increased excretion of sodium, caused by furosemide].

In the cells of nephron tubules an effect of furosemide on kidney function and on succinate dehydrogenase and Na+-K+-ATPase activities was studied cytochemically. Administration of furosemide (1 mg per 100 g of body weight) increased excretion of sodium and potassium. If the rate of filtration through Malpighian tufts was constant, the increase in Na and K excretion demonstrated the tubular effect of the diuretics. Both administration of furosemide and preincubation of the drug with kidney slices in vitro caused a decrease in succinate dehydrogenase activity in the cells of all the nephron sections. These data suggest that a direct effect of the diuretics on oxidative metabolism in renal cells took place. Alteration in the activity of Na+-K+-ATPase was observed only in vivo and in those nephron sections, where sodium reabsorption was decreased under the effect of furosemide.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Estimation of hearing in patients with end stage renal failure being peritoneally dialyzed with and without furosemide in the dialysis fluid].

The purpose of our study was to estimate hearing state and effect of intraperitoneal administration of furosemide on an organ of hearing in the patients with end-stage renal failure being treated with intermittent peritoneal dialysis. Ten patients divided into two groups, were observed for three months. A weekly dosage of 1.2-2.0 g of furosemide was administered to the patients of first group while the patients of second group were not given furosemide. Based upon the studies, which had been carried out by pure tone audiometry method and Fowler's test and Belesy's audiometry, it was found the lesion of hearing, mainly in the range of higher frequency, having a character of cochlear hypoacusia. The further lesion of hearing was not seen within three months of regular treatment with intermittent peritoneal dialysis. The audiometric studies which had been carried out in different stages of treatment, did not show ototoxicity influence of furosemide added to dialysis fluid.

Adult↗
PubMedDate not supplied

The effect of inhaled furosemide and acetazolamide on bronchoconstriction induced by deep inspiration in asthma.

In some asthmatics deep inspiration causes a sustained bronchoconstration, which is dependent on Ca2+ uptake. Inhaled diuretics protect against bronchoconstriction induced by a variety of indirect stimuli, by inhibiting the ionic fluxes involving Ca2+ uptake across the cell membrane of airway epithelium. The aim of this study was therefore to investigate the protective effect of inhaled furosemide on the bronchoconstriction induced by deep inspiration in asthma and to compare it with the effect of acetazolamide, an inhibitor of carbonic anhydrase devoid of effect on ion cotransport but possessing inhibitory effects on chloride ion influx and Na+/K+ exchange. The study was carried out on three different study days according to a randomized, double-blind, placebo-controlled, crossover design. Nine non smoking asthmatic subjects first performed a series of 9 controlled deep inspirations to TLC followed by forced expirations to RV within 20 min, which caused a decrease of FEV1 > 20% from baseline. Two hours later, the subjects inhaled either furosemide (40 mg), or acetazolamide (500 mg), or saline (placebo) in random order, and then two more deep-inspiration challenges were performed after 30 and 140 mins. The progressive percent decrement of FEV1 caused by deep-inspiration challenge was taken as an index of bronchoconstriction. Bronchoconstriction was significantly blunted at 30 mins, but not 140 mins, after inhaling furosemide (p < 0.01) or acetazolamide (p < 0.05) compared to control. We interpret these results as due to a modulation of ionic fluxes across the smooth muscle cell membrane afforded by inhaled furosemide and acetazolamide.

Acetazolamide↗
PubMed1992

Effects of furosemide and pentoxifylline on blood flow properties in horses.

The effects of furosemide and pentoxifylline on blood flow properties in horses were investigated. Hematologic and rheologic changes were examined in 4 horses before and 3 minutes after administration of epinephrine (1 mg, IV). The next day, hemorheologic changes were determined before and 3 hours after administration of furosemide (1 mg/kg of body weight, IM), and after administration of epinephrine at the sampling at 3 hours. Hematologic and rheologic changes were evaluated weekly in 3 horses given pentoxifylline (8.5 mg/kg, q 12 h, PO) for 28 days. In addition, hemorheologic responses to epinephrine were determined on days 0, 14, and 28 of pentoxifylline treatment. Neutrophil filtration studies were also performed 2 hours after IV administration of pentoxifylline (8.5 mg/kg). Postepinephrine values for PCV, RBC and WBC counts, and blood viscosity were greater than preepinephrine values. Erythrocyte sedimentation rates decreased after epinephrine, whereas RBC filterability did not change. Treatment with furosemide was associated with increases in mean RBC hemoglobin concentration and blood viscosity. Filterability of RBC did not change. Treatment with pentoxifyllie resulted in an increase in RBC filterability and erythrocyte sedimentation rate and a decrease in PCV; however, mean values for hematocrit and RBC count did not change. Treatment with pentoxifylline did not result in a change in resting blood viscosity, but markedly reduced the postepinephrine increase in blood viscosity. Neither IV nor orally administered pentoxifylline had an effect on neutrophil filtration. It was concluded that pentoxifylline has beneficial effects on RBC filterability and postepinephrine changes in blood viscosity, which may contribute to improvements of microcirculatory blood flow. In addition, furosemide may exacerbate exercise-associated hyperviscosity in horses.

Animals↗
PubMed1992

[Effects of furosemide, propranolol and nifedipine on urinary excretion of Tamm-Horsfall protein in patients with arterial hypertension].

UNLABELLED: In 65 hypertensive patients the influence of 10 day treatment with furosemide (24 subjects), nifedipine (21 subjects) and propranolol (20 subjects) respectively on urinary Tamm-Horsfall protein (U-THP), sodium and potassium excretion, 24 hour urinary volume and blood pressure was determined. In 23 control subjects the above mentioned parameters were assessed only under basal conditions. In hypertensive patients urinary THP excretion was not different from controls. In all examined groups a significant positive correlation was found between urine volume and urinary THP excretion under basal conditions. Such a correlation was absent after nifedipine or propranolol therapy respectively, but still existed after furosemide administration. No correlation was found between urinary THP and Na and K excretion respectively. In contrast to nifedipine and propranolol, a 10 day treatment with furosemide caused a significant increase in U-THP. CONCLUSIONS: Urinary THP excretion in hypertensive patients did not differ from U-THP in healthy subjects. In contrast to propranolol and nifedipine, treatment with furosemide caused an increase in THP urinary excretion.

Adult↗
PubMed2003

Effect of furosemide on urine specific gravity and osmolality in thoroughbred racehorses.

Postrace urine samples from thoroughbred horses were examined to compare osmolality and specific gravity between horses treated with furosemide and those not treated. Samples were assigned to groups in relation to reported medication (furosemide) status, race finish position, and distance of race. Urine osmolality was significantly (P <.05) lower in samples from horses treated with furosemide when compared with untreated horses. Specific gravity determinations are less precise at measuring urine osmolality at lower levels (1.01 g/ml or less). The measurement of osmolality is a superior method for determining the urine solute concentration and facilitating the regulation of furosemide.

Animals↗
PubMed2004

Comparative study of the efficacy of potassium magnesium L-, D- and DL-aspartate stereoisomers in overcoming digoxin- and furosemide-induced potassium and magnesium depletions.

Potassium and magnesium aspartate (K,Mg aspartate) is used in treating and preventing cardiac disruptions caused by electrolytic disturbances, primarily low potassium (K) and magnesium (Mg) levels (e.g. in the treatment with cardiac glycosides and diuretic drugs). Widely used, K,Mg aspartate is synthesized from aspartic acid representing a racemic mix of L- and D-stereoisomers. Differences in metabolism and utilisation of D- and L-amino acids probably have an effect on the pharmacological properties of K,Mg L- and D-aspartates, and what is more, pharmacological doses of magnesium and potassium salts may induce toxicity, which differs according to the nature of the anions. Therefore, the purpose of the present work was to study the effect of intravenously administered K,Mg L-aspartate in comparison with its D- and DL-stereoisomers on K and Mg restoration rates in plasma, erythrocytes and myocardium and to evaluate the urine excretion rate of amine nitrogen and Mg in digoxin and furosemide treated rats. To induce Mg depletion, male rats, weighing 180-200 g, were given furosemide and digoxin at doses of 30 mg/kg (i.p.) and 0.25 mg/kg (i.p.) daily for 14 days. After 14 days K,Mg L-, D- and DL-aspartates were administered with simultaneous furosemide and digoxin treating at dose of 100 mg/kg (i.v.), which corresponds to 46.95 mg of Mg aspartate (i.e. Mg = 3.96 mg) and 53.05 mg of K aspartate (i.e. K = 12.12 mg) per kg bodyweight. Erythrocyte, plasma and urine Mg levels were measured by colorimetric assay using the method based on the staining reaction of Mg and thiazole yellow. Myocardium Mg and K content and erythrocyte K levels were determined by flame atomic absorption spectroscopy. The level of amine nitrogen was measured by colorimetric assay using the method based on the staining reaction with ninhydrin. It was shown that K,Mg L-aspartate administration leads to higher compensation of K and Mg deficiency in rats with furosemide and digoxin induced K and Mg depletion, as compared with D- and DL-stereoisomers. According to the K and Mg deficiency correction rate, K,Mg aspartates may be ranged in the following order: K, Mg L-aspartate > K,Mg DL-aspartate > K,Mg D-aspartate. It was shown that after administration of K,Mg L-aspartate, daily urine excretion of amine nitrogen and Mg is less than after D- and DL-stereoisomer administration. According to the quantity of excreted amine nitrogen and Mg in urine, K,Mg aspartates may be ranged in the following order: K,Mg D-aspartate = K, Mg DL-aspartate > K,Mg L-aspartate. So, K,Mg L-aspartate is more beneficial in the treatment of several forms of primary Mg and K deficiency than K,Mg DL-aspartate and K, Mg D-aspartate.

Amines↗
PubMedDate not supplied

[Effect of furosemide on GABAA-induced 36Cl transport on ATPase activity in synaptic membranes of carp (Cyprinus carpio L.)].

We studied the effect of furosemide on GABAA-induced 36Cl transport and GABAA-induced Cl- -ATPase activity in synaptic membranes of fish brain. At physiological pH of 7.4, GABA (0.1-100 microM) stimulated 36Cl transport in synaptoneurosomes and Cl- -ATPase activity in synaptic membranes. Furosemide (0.1-0.5 mM) removed the activating effect of the mediator on chlorine transport and enzyme activity (I50 equaled 0.16 and 0.12 mM, respectively). In the absence of the mediator, picrotoxin (50 microM) activated the basal 36Cl influx in synaptoneurosomes and the basal Mg2+ -ATPase activity of synaptic membranes. Furosemide (1 mM) removed the activating effect of picrotoxin on both biochemical processes. The obtained data demonstrated similar sensitivities of GABAA-induced transport of 36Cl in synaptoneurosomes and of GABAA-induced Cl- -ATPase activity in synaptic membranes to furosemide and indicated the involvement of the ATPase in GABAA-induced processes. The soluble ATPase, recovered by sodium deoxycholate solubilization of the membranes, remained sensitive to GABAA-ergic ligands, which suggested proximity of their binding sites with ATP hydrolysis sites of protein molecule and their structural contingency.

Adenosine Triphosphatases↗