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PubMedDate not supplied

Effect of glycerol on furosemide-caused EP decrease in guinea pig neonates.

Furosemide, a loop diuretic, reduces the endocochlear potential in guinea pigs. In our previous experiment using adult guinea pigs, glycerol was thought to open the blood-cochlea barrier and to help furosemide to reach its site of action in the stria vascularis. The present study was designed to determine whether or not the same potentiation by glycerol occurs in neonate guinea pigs. In one group, furosemide (10-30 mg/kg) was administered, while in another group, 50 v/v% glycerol (1 ml/kg) was administered 15 minutes prior to the injection of furosemide. Furosemide reduced the EP significantly more in neonates than in adults. This effect was not potentiated in the glycerol-pretreated group. From these findings, it seemed conceivable that the neonate blood-cochlea barrier still remains immature in some functions.

Animals↗
PubMedDate not supplied

Comparative ototoxicity of furosemide and piretanide.

The purpose of these studies was to compare the ototoxicity of piretanide to that of furosemide in the chinchilla. Chinchillas weighing 400 to 700 g were anesthetized with ketamine plus pentobarbital. Endocochlear potential (EP) was measured continuously by the round window approach using glass microelectrodes. Piretanide or furosemide injected through a jugular vein catheter in adults range from 10-100 mg/kg. Little or no change in EP was noted with doses below 15 mg/kg of either diuretic. The overall pattern of decline of EP was rather similar in piretanide-treated and furosemide-injected animals, and it was interesting to find that the dose-ototoxicity response curve for piretanide was similar to that for furosemide. The diuretic effect of equal ototoxic doses of either diuretic was equivalent. Both diuretics cause a decrease of endocochlear potential when applied locally to the round window membrane of the chinchilla as well as by systemic administration. These findings suggest that piretanide and furosemide have approximately the same propensity for ototoxicity.

Administration, Topical↗
PubMed1994

Decrease in the time-dependent difference in urinary excretion of furosemide with age.

The influence of age on the time-dependent difference in urinary excretion of furosemide, a loop diuretic agent, was examined in this longitudinal study. Male Wistar rats were maintained under conditions of light from 07:00 to 19:00 h and dark from 19:00 to 07:00 h. Furosemide (30 mg/kg) was given orally at 12:00 h (day trial) or 00:00 h (night trial) to rats at 3 months of age, and urine was collected for 8 h after dosage. Thereafter, the identical protocol was repeated using the same animals at 6, 9, 12, 15, 18, and 21 months of age. The urinary excretion of furosemide was significantly greater in the day than in the night trial at 3 months of age. Such a time-dependent difference was observed for up to 15 months, but disappeared at 18 and 21 months of age. The time-dependent difference in urinary excretion of furosemide (day trial - night trial) decreased gradually throughout the observation period of the study. These results suggest that the time-dependent difference in the urinary excretion of furosemide diminishes during the aging process and disappears by 18 months of age in male Wistar rats.

Administration, Oral↗
PubMed1984

Synchronous changes in active and inactive renin secretion after furosemide in patients with primary aldosteronism.

Changes in plasma active and inactive renin concentrations (ARC and IRC) were measured in 10 patients with primary aldosteronism (PA) due to adrenal adenomas. Before the resection of adrenal adenomas, venous blood samples were taken at supine resting state, after 1-hour standing and 30 min. after furosemide injection and these samplings were repeated after surgical treatment. Plasma inactive renin was measured after activation with trypsin. Before the treatment ARC and IRC did not change by standing or furosemide. After the treatment, however, ARC was increased clearly by standing or furosemide, and IRC was also increased by furosemide injection. Both ARC and IRC at supine resting state were increased after the surgery. When the renin-angiotensin system is suppressed chronically by the over-produced aldosterone in patients with PA, not only active but also inactive renin secretions are suppressed, and fail to respond to orthostasis or furosemide. The secretion of IR could be stimulated after the removal of aldosteronoma.

Adenoma↗
PubMed1991

Dissociation of plasma atrial natriuretic peptide responses to upright posture and furosemide administration in patients with normal-, low renin essential hypertension and primary aldosteronism.

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6 +/- 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8 +/- 6 pg/ml), IHA (54.1 +/- 6.3 pg/ml) and APA before (62.4 +/- 4.9 pg/ml) but not after adrenal surgery (22 +/- 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p less than 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.

Adult↗
PubMed1986

Interaction of furosemide and phenytoin in the rat.

The interaction of phenytoin and furosemide was examined in rats. After 2 or more weeks of pretreatment with phenytoin, the diuretic activity of furosemide given orally was decreased. This was due primarily to a generalized decrease in absorption from the gastrointestinal tract. Following intravenous administration of furosemide to phenytoin pretreated rats, a decrease in diuretic activity also occurred. Excretion of furosemide was not altered. Thus, phenytoin pretreatment would also appear to interfere directly with the renal action of furosemide.

Administration, Oral↗
PubMed2004

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

INTRODUCTION: A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE: In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS: Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS: Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION: Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.

Adult↗
PubMed1990

[Effects of long-term administration of furosemide on calcium balance, kidney and parathyroid gland].

Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Renal response to captopril in severe heart failure: role of furosemide in natriuresis and reversal of hyponatremia.

To assess the effect of furosemide and captopril on renal function and hyponatremia in patients with severe heart failure, we studied two groups of patients with hyponatremia who were receiving digoxin therapy and whose sodium intake was 40 meq/d. One group received captopril and furosemide, the second received captopril. The first group responded to combination therapy with a brisk natriuresis and diuresis, weight reduction, and an increase in serum sodium concentration. Patients who received captopril alone did not respond, despite a similar increase in renal plasma flow and glomerular filtration rate. When furosemide was then administered to patients who had received captopril alone, a brisk natriuresis, weight loss, and correction of hyponatremia followed. Treatment with furosemide is necessary to promote natriuresis and correction of hyponatremia in patients with severe heart failure treated with captopril; the renal vascular action of captopril enhances the effectiveness of furosemide.

Adult↗
PubMed1976

Effect of furosemide on renal hilar lymph flow.

Furosemide is known to increase total renal blood flow. The purpose of this study was to determine the relationship between this hemodynamic change and renal hilar lymph flow. Renal blood flow was measured with an electromagnetic flowmeter placed on the left renal artery of anesthetized dogs. Lymph was collected from a cannulated hilar vessel. Urine volume loss was not replaced. In the first 10 min after furosemide (1 mg/kg i.v.), lymph flow was significantly increased and then declined toward control within 30 to 40 min. The decline in lymph flow lagged behind the decline in blood flow by about 10 min. In 11 experiments in which there was a significant increase in renal blood flow, renal hilar lymph flow also increased. In 5 experiments in which renal blood flow did not increase after furosemide, lymph flow also did not increase. In both groups, urine volume was significantly increased but the diuresis was less in the group in which renal blood flow and lymph did not increase. When hydrochlorothiazide (5 mg/kg, i.v.) was administered, neither renal blood flow nor hilar lymph flow was altered. The effect of equi-diuretic doses of furosemide and hydrochlorothiazide on renal tissue water content were compared. The amount of water present after furosemide was significantly greater than the amount present after hydrochlorothiazide. These data support the concept that changes in renal hilar lymph flow are more a consequence of changes in renal blood flow than in urine volume.

Animals↗
PubMed1999

Enhanced absorption of oral furosemide by bile juice in rats.

The effect of bile juice on gastrointestinal absorption of furosemide was investigated in rats. Furosemide intravenous solution (Lasix), 20 mg/kg, was administered orally with (n = 5) or without (n = 6) bile juice administration after bile duct cannulation. With bile juice administration, the plasma concentrations of furosemide were considerably higher and AUC(0-8) h was significantly greater (2570 versus 658 microg x min/ml) suggesting that absorption of furosemide increased significantly by bile juice. This was supported by significantly smaller in the percentages of oral dose of furosemide recovered from entire gastrointestinal tract at 24 h: the values were 29.5% and 58.0% with and without bile juice administration, respectively.

Administration, Oral↗
PubMed2000

Endogenous bradykinin and the renin and pressor responses to furosemide in humans.

In humans, bradykinin contributes to the acute renin response after ACE inhibition. To further explore the role of endogenous bradykinin in human renin regulation, we determined the effect of HOE 140, a specific bradykinin B(2) receptor antagonist, on the renin response to 0.5 mg/kg i.v. furosemide in a randomized, single blind, crossover design study of 10 healthy, salt-replete volunteers. HOE 140 did not affect basal plasma renin activity, aldosterone, mean arterial pressure, or heart rate. Furosemide administration increased plasma renin activity from 1.0 +/- 0.2 to 4.5 +/- 1.2 ng of angiotensin I/ml/h and there was no effect of HOE 140 (from 1.1 +/- 0.2 to 3.9 +/- 0.8 ng of angiotensin I/ml/h). Similarly, there was no effect of HOE 140 on the diuretic response to furosemide. Mean arterial pressure increased in response to furosemide after HOE 140 (82 +/- 2 to 94 +/- 2 mm Hg), but not after vehicle (81 +/- 3 to 85 +/- 2 mm Hg), whereas heart rate was unchanged. In conclusion, activation of the B(2) receptor by endogenous bradykinin does not contribute to the renin response to acute furosemide treatment in humans. However, bradykinin may contribute to blood pressure regulation under conditions in which the renin-angiotensin system is stimulated.

Adrenergic beta-Antagonists↗
PubMed1975

Method of collecting urine and comparative investigation of quantities excreted by cats and dogs after administration of furosemide.

A method is described for precise investigation of diuresis and saluresis in cats, using trained animals in a special diuresis apparatus. Furosemide given intramuscularly (IM) to cats at the dose level of 10 mg/kg produced slight untoward reactions of short duration. Therefore, this dose lies at the upper limit of tolerance. Saluretic and diuretic effect of 5 different doses of furosemide was investigated in 4 cats and 20 dogs. A dose-dependent increase in diuresis was achieved in cats given doses of furosemide ranging from 1.25 to 10 mg/kg. In the dog, the range of effectiveness was broader. In both species, there was a parallel increase in the excretion of sodium and chloride ions. The excretion of potassium ions in the cat remained unaffected, whereas in the dog, there was a dose-dependent increase in potassium ion excretion, which became especially distinct when large doses were given. A direct comparison of total saluretic and diuretic values in the dog and cat after IM administration of furosemide was not possible, since the calculated straight lines had different slopes, and their points of intersection lay outside the scope of this study. A difference can be assumed to exist between dog and cat in the mode of action of diuresis and saluresis after administration of furosemide.

Animals↗
PubMedDate not supplied

Furosemide plus albuterol compared with albuterol alone in children with acute asthma.

Several reports have shown that inhaled furosemide protects patients with asthma from different bronchoconstrictor agents. However, the effect of this widely used diuretic in acute exacerbation in adults is unproven. There are no reports of furosemide's therapeutic effect in acute asthma in children; thus, the objective of this study was to determine the effectiveness of the combined treatment of furosemide and albuterol in pediatric patients. Using a double-blind design, 20 emergency room patients with an asthmatic exacerbation were studied and randomly assigned to one of the following treatments: (1) furosemide + albuterol (1 and 0.15 mg/kg, respectively) or (2) albuterol (0.15 mg/kg). The forced expiratory volume in one second (FEV1) was measured in each patient before medication and then 30 and 60 minutes after inhalation of the individual drug or drug combination. Neither group differed in age or baseline FEV1. An increase in FEV1 of 22.8 +/- 4.3% (mean +/- SE) in the drug combination group was noted at 60 minutes, and an increase in FEV1 of 18.0 +/- 2.6% in the albuterol group was obtained at the same time. Although the increase in FEV1 was greater in the first group after 1 hour of treatment, this was not significant. These results suggest that inhaled furosemide does not have a synergistic effect with albuterol in the treatment of asthmatic exacerbations in children.

Acute Disease↗
PubMed1975

Effect of ouabain on the renal response to furosemide.

The aim of this work was to investigate whether the natriuretic effect of furosemide can be wholly explained by the inhibition of a ouabain-sensitive Cl transport in the thick ascending limb of Henle. For this purpose 6 dogs undergoing moderate saline diuresis received 100 mug ouabain/kg into the left renal artery followed by 2 mg furosemide/kg IV. Urine was collected from both kidneys and blood samples taken at regular intervals. Ouabain produced a unilateral increase in Na excretion and little change in CCR and water and K excretion. IV furosemide increased Na, K and water excretion in both kidneys. Since Na excretion in the left kidney was already exhanced by ouabain the increment was lesser than in the right kidney. As a result water and electrolyte excretion became similar in both kidneys. Although ouabain did not prevent the renal response to furosemide, the effects of both drugs were not additive. This suggests that in addition to the thick ascending limb, furosemide acts in some other tubular segment which is insensitive to ouabain. Since furosemide is known to also inhibit passive Cl movements, a second site of action could be in the thin ascending limb of Henle, which lacks any active transport mechanism but is highly permeable to Cl.

Animals↗
PubMed2002

Comparison of serum and urinary concentrations of clenbuterol with and without concomitant administration of furosemide in horses.

Furosemide is frequently used to control or prevent exercise-induced pulmonary hemorrhage in performance horses. The bronchodilating agent clenbuterol is also commonly used as a treatment for inflammatory airway disease in performance horses. Use of both medications is regulated by many racing authorities. The effects of concomitant administration of furosemide and clenbuterol on the pharmacokinetics of clenbuterol have not been well characterized. A study was designed to evaluate the influence of furosemide on serum and urine concentrations of clenbuterol after oral administration of clenbuterol and intravenous administration of furosemide in horses. Results indicated that urinary concentrations of clenbuterol in horses treated concomitantly with furosemide and clenbuterol were increased, whereas serum concentrations of the drug were decreased. These effects persisted during the study period and varied among horses.

Animals↗
PubMedDate not supplied

[Effect of furosemide on water and sodium excretion in apparently normal infants].

Nine infants without evidence of nephropathy were studied. After a control period, furosemide, 1.0 mg/kg. of body weight, was administered intravenously and urine was collected. In all patients, urinary volume increased from a mean of 0.15 ml/min. during the control period, to 0.69 ml/min. after furosemide and urinary sodium excretion rose from 1.77 micro Eq/min. in the first period, to 50.13 micro Eq/min. in the second. There was no significant change in urinary osmolarity and in serum electrolytes. Three hours after furosemide, all children showed dehydration from light to moderate and saline infusion was necessary. No correlation was found between age and weight of the infants with the response to furosemide. Because this diuretic has an energetic action in infants as in children and adults, it must be used carefully and it is proposed that the initial dose of furosemide in infants be 0.5 mg/kg.

Age Factors↗
PubMed2003

Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers.

The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of furosemide following gastroretentive dosage from (GRDF) administration. A furosemide (60 mg) GRDF, releasing the drug during 6 hours in vitro, or an immediate-release tablet was administered to healthy male volunteers (N = 14) in a crossover design. Food and liquid intake were standardized; urine was collected, weighed, and assayed for furosemide and sodium concentrations. Pharmacokinetics of furosemide following the GRDF administration, as compared to the tablet, showed lower Cmax and indicated a prolonged absorption phase leading to longer mean residence time in the stomach. The sustained input of the drug significantly improved diuretic and natriuretic efficiencies during the first 5 hours and thereby increased the total effects measured over 24 hours. The unfolding controlled-release GRDF of furosemide improved the pharmacodynamic actions due to the sustained absorption in the stomach and jejunum, which delayed the body's counteractivity to the drug effect.

Adult↗