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PubMed1996

Tachyphylaxis to furosemide in isolated airways of guinea pigs.

This in vitro study was conducted to determine whether tachyphylaxis of guinea pig airway to furosemide occurs under conditions that produce tachyphylaxis to the beta 2-adrenoceptor agonist, salbutamol. Isometric tension was measured in tracheal rings bathed in HEPES buffer from 4-6 d newborn guinea pigs of either sex, and 6 wk old males. Paired rings were first incubated with furosemide, 30 or 300 microM, or control for 60 min, washed, then constricted with 3 microM acetylcholine. At stable contraction, relaxation to furosemide (30 microM-1 mM) was measured. For comparison, similar experiments were performed with 10 microM salbutamol incubation for 30 min. 86Rb uptake, a marker for K+ transport and Na-K-Cl cotransport activity, was also measured in these airway segments. Pre-exposure to these airway relaxants did not affect contractile force generation by acetylcholine. Tracheal desensitization to both salbutamol and furosemide was observed. Partial recovery of furosemide induced relaxation was seen one hour after desensitization. Pre-exposure to 300 microM furosemide did not inhibit the decrease in 86Rb uptake normally observed with furosemide. In summary, we found that: 1) tachyphylaxis of guinea pig airway relaxation occurred with both salbutamol and furosemide under similar experimental conditions; however 2) inhibition of 86Rb uptake by furosemide was not affected by prior exposure. Taken together, these results suggest that furosemide induced airway relaxation could be affected by repeated or prolonged exposure, but this response may not be associated with changes in furosemide-sensitive Na-K-Cl cotransporter activity.

Albuterol↗

PubMed1992

Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia.

A decreased response to the loop diuretic furosemide develops within a few doses in young infants. We tested the hypothesis that the use of the thiazide-like diuretic metolazone, in combination with furosemide, would inhibit water and electrolyte reabsorption and overcome pharmacologic tolerance to furosemide alone. Infants with bronchopulmonary dysplasia of similar gestational and postnatal ages were randomly assigned to one of three groups. Group 1 (n = 6) received furosemide (1 mg/kg per dose) intravenously every 24 hours for a total of five doses. Group 2 (n = 8) received the same treatment as group 1, but in addition metolazone (0.2 mg/kg per dose) was given enterally with doses 3 and 4 of furosemide. Group 3 (n = 8) received metolazone (0.2 mg/kg per dose) enterally every 24 hours for five doses. Urine was collected before the first diuretic dose and throughout the study for determination of the urine flow rate; urinary excretion of sodium, chloride, and potassium; and creatinine clearance. Urinary flow rate and urinary sodium and chloride excretion increased after the first dose in all groups. In the infants treated with either furosemide or metolazone, urinary flow rate and urinary and chloride excretion returned to baseline values after the last three doses. In contrast, when furosemide was administered with metolazone, urinary flow rate and urinary excretion of sodium, chloride, and potassium were greater than the values for baseline and for the previous dose, as well as for the corresponding doses of furosemide in group 1 and metolazone in group 3. Tolerance to furosemide (group 1) and metolazone (group 3) appeared to be explained by compensatory increased sodium and chloride reabsorption without changes in creatinine clearance. We conclude that the administration of metolazone with furosemide enhances diuresis, natriuresis, and chloruresis and overcomes the rapid development of tolerance to furosemide in infants with bronchopulmonary dysplasia by blocking the compensatory increase in renal sodium and chloride absorption.

Bronchopulmonary Dysplasia↗

PubMed1981

Effect of furosemide in congestive heart failure.

The diuretic effect of furosemide was studied in 18 patients with congestive heart failure. Subjects were divided into two groups, group I consisting of eight patients with moderate and group II of 10 patients with advanced congestive heart failure. Six hours after bolus injection of furosemide (40 mg), mean urinary sodium was 120.5 +/- 36.7 mEq in group I and 68.2 +/- 25.8 mEq in group II (p less than 0.01), mean urine volume was 1,100 +/- 281 and 764 +/- 257 ml (p less than 0.05), mean urinary furosemide excretion was 28.08 +/- 2.60 and 24.00 +/- 0.74 mg (p less than 0.05), and mean furosemide renal clearance was 73.4 +/- 16.6 and 42.3 +/- 11.5 ml/min (p less than 0.001). Diuretic effect and furosemide renal clearance, as well as urinary furosemide excretion, correlated positively. The diuretic effect of furosemide with and without hydralazine (0.2 mg/kg) was compared in eight patients in group II. Urinary sodium excretion 6 hr after furosemide rose from 77.2 +/- 31.0 to 122.8 +/- 42.5 mEq after furosemide with hydralazine (p less than 0.01). Urine volume rose from 854 +/- 278 to 1,279 +/- 359 ml (p less than 0.001), urinary furosemide excretion rose from 23.64 +/- 2.03 to 26.94 +/- 2.30 mg (p less than 0.01), and furosemide renal clearance rose from 46.3 +/- 12.2 to 62.5 +/- 18.6 ml/min (p less than 0.01).

Adult↗

PubMed1987

Inhibition of renal clearance of furosemide by pentopril, an angiotensin-converting enzyme inhibitor.

The pharmacokinetic interaction between pentopril (250 mg) and furosemide (40 mg) was studied in 12 normal healthy volunteers after oral administration of each drug alone and in combination. No significant changes in any pharmacokinetic parameters of pentopril or its active metabolite (CGS 13934) were observed on coadministration of furosemide. In contrast, pentopril induced significant changes in disposition of furosemide. Pentopril decreased renal clearance (CLR) of furosemide by 54% and the fraction excreted unchanged in urine also decreased by 55%. However, such decrease in CLR of furosemide was compensated by a simultaneous increase in glucuronidation (by 200%), resulting in a slight increase in systemic clearance (decreased AUC). Systemic bioavailability of furosemide appears to be unchanged in the presence of pentopril (0.46 vs. 0.41). No effect of pentopril on plasma protein binding of furosemide was detected. In spite of the decreased CLR and urinary excretion rate of furosemide, the urinary output (1749 vs. 1774 ml/6 hr) and Na+ excretion (757 vs. 816 mEq/6 hr) remained almost unchanged. These findings suggest that total furosemide (unchanged and glucuronide) might contribute to diuresis and natriuresis rather than the unchanged furosemide alone. Because of unchanged pharmacodynamic effect, such pharmacokinetic interaction may not require any dosage adjustment for furosemide on pentopril coadministration.

Administration, Oral↗

PubMed2000

Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses.

The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre-exercise)-control, and furosemide (250 mg i.v., 4 h pre-exercise)+clenbuterol (0.8 microg/kg i.v., 11 min pre-exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub-maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide-control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide-control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood-gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH.

Adrenergic beta-Agonists↗

PubMed2002

Effect of mannitol and furosemide on plasma osmolality and brain water.

BACKGROUND: Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might occur is via a reduction in brain water content. Although mannitol and furosemide are commonly used in combination, there has been no formal evaluation of the interactive effects of these two drugs on brain water. The effect of mannitol and furosemide alone and in combination on water content of normal rat brain was examined. METHODS: The lungs of rats anesthetized with halothane were mechanically ventilated to maintain normal physiologic parameters. After baseline measurement of plasma osmolality, mannitol (1, 4, or 8 g/kg), furosemide (2, 4, or 8 mg/kg), or a combination of furosemide (8 mg/kg) and mannitol (1, 4, or 8 g/kg) was administered intravenously over approximately 15 min. One hour later, plasma osmolality was measured, the animals were killed, and brain water content was determined by wet and dry weight measurements. RESULTS: Mannitol produced a dose-dependent increase in plasma osmolality and reduction of brain water content. There was a linear relation between plasma osmolality and brain water content. Furosemide alone did not affect plasma osmolality or brain water at any dose. The combination of furosemide with mannitol resulted in a greater increase in plasma osmolality than seen with mannitol alone and a greater decrease in brain water at 4 and 8 g/kg of mannitol. CONCLUSIONS: The doses of mannitol and furosemide utilized were much larger than clinically applicable doses and were selected to maximize the ability to detect effect on brain water. The combination of mannitol and furosemide resulted in greater reduction of brain water content than did mannitol alone. Furosemide enhanced the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content. Potential interaction (if any) of smaller, clinically used doses of mannitol and furosemide cannot be surmised from the current study.

Animals↗

PubMed2000

Furosemide inhibits thromboxane A2-induced contraction in isolated human internal mammary artery and saphenous vein.

Evidence suggests that, in addition to its diuretic property, furosemide also may exert direct vascular effects. Because thromboxane A2 (TXA2) has a role in the control of vascular tone, we investigated the effect of furosemide on the contraction induced by U46619 (a stable TXA2 mimetic) on isolated human internal mammary artery (IMA) and saphenous vein (SV). Concentration-response curves to U46619 were performed in the absence (vehicle) or the presence of furosemide (0.1-1 mM) on rings of IMA and SV. In addition, the relaxant effect of furosemide (0.1 microM-1 mM) also was evaluated on U46619-precontracted IMA and SV. The participation of cyclooxygenase derivatives was studied by pretreatment with indomethacin. Furosemide (0.1-1.0 mM) caused parallel rightward shifts of U46619 concentration-response curves without affecting the maximal responses in both IMA and SV. Treatment with indomethacin (1 microM) modified neither the inhibitory effect of furosemide on U46619-induced contractions, nor the relaxant effect of furosemide on U46619-induced contractions, nor the relaxant effect of furosemide on U46619-precontracted IMA and SV. In conclusion, furosemide at high concentrations inhibited U46619-induced contraction in human isolated IMA and SV and relaxed U46619-precontracted IMA and SV by mechanisms independent of the release of relaxant prostaglandins. These results suggest that blockade of TXA2 receptors by furosemide may contribute to explaining the therapeutic effects of furosemide in the treatment of severe heart failure.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1990

The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses.

A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fentanyl, the data generated were insufficient to state with certainty whether or not furosemide affected the plasma concentrations of these three drugs. A significant reduction was noted in the urinary concentrations of guaifenesin, acepromazine, clenbuterol, phenylbutazone, flunixin, fentanyl and pentazocine within 1-4 h of furosemide administration. The urinary concentrations of theophylline remained reduced as long as 8 h after furosemide injection. Furosemide administration to horses pre-treated with codeine resulted in depression of urinary morphine concentrations 2-4 h and 9-12 h after furosemide injection. A lower furosemide dose (150 mg) produced changes in drug urinary excretion and plasma elimination equivalent to the higher dose (250 mg). It is evident that furosemide affects the urinary and plasma concentrations of other co-administered drugs but not in a predictable fashion, which limits the extrapolation of these results to as yet untested drugs.

Acepromazine↗

PubMed1992

Renal effects of alpha-adrenoceptor blockade during furosemide diuresis in conscious rats.

Clearance experiments were performed in conscious rats in order to investigate whether intravenous infusion of the non-selective alpha-adrenoceptor antagonist phentolamine could block compensatory sodium reabsorption during furosemide-induced volume contraction. By measuring inulin clearance, urinary excretion rates of sodium and water, and lithium clearance, the effects on proximal and distal nephron segments were dissociated. The renal effect of intravenous infusion of 0.3 mg/kg/hr phentolamine (n = 6) was compared with time control animals (n = 9). Furosemide was administered as constant intravenous infusion (7.5 mg/kg/hr) with simultaneous phentolamine infusion at four dose levels: 0 (n = 9), 0.3 (n = 6), 1.0 (n = 7) and 3.0 mg/kg/hr (n = 6). Phentolamine infusion reduced norepinephrine-induced increase in blood pressure at all three dose levels (n = 5). Phentolamine infusion induced transient antidiuresis and a prolonged antinatriuretic response. Compared with rats given furosemide only, phentolamine attenuated dose-dependently the diuretic and natriuretic peak response to furosemide. This effect was associated with dose-dependent reductions in mean arterial pressure. The reduced natriuretic response was due to a reduced fractional sodium excretion in the distal nephron segment (at all doses of phentolamine) and a reduction of the glomerular filtration rate (1.0 and 3.0 mg/kg/hr phentolamine). The fractional lithium excretion (FELi) increased to 65 +/- 3% at 0.3 mg/kg/hr phentolamine during the natriuretic peak response of furosemide, while it only increased to 52 +/- 3% during furosemide alone. At steady-state conditions (120-180 min. after start of furosemide infusion) after infusion with furosemide plus 0.3 mg/kg/hr phentolamine the animals were still volume-depleted, but the compensatory tubular Na reabsorption in the proximal tubules was inhibited (FELi = 48 +/- 2% versus 39 +/- 1% in rats given furosemide alone). During furosemide infusion plasma epinephrine increased 700% and plasma norepinephrine increased 50%. These results are compatible with increased systemic sympathetic nervous activity and a contributory role of proximal tubular alpha-adrenoceptors in mediating compensatory sodium reabsorption during acute furosemide-induced volume contraction.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Pharmacology of furosemide in the horse: a review.

Furosemide, a diuretic, is frequently administered to horses for the prophylaxis of exercise-induced pulmonary hemorrhage and the treatment of a number of clinical conditions, including acute renal failure and congestive heart failure. Furosemide increases the rate of urinary sodium, chloride, and hydrogen ion excretion. Plasma potassium concentration decreases after furosemide administration but urinary potassium excretion in horses is minimally affected. Renal blood flow increases after furosemide administration. Systemically, furosemide increases venous compliance and decreases right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and pulmonary blood volume. The systemic hemodynamic effects of furosemide are only manifest in the presence of a functional kidney, but can occur in the absence of diuresis, emphasizing the importance of the renal-dependent extra-renal effects of furosemide. The renal and systemic hemodynamic effects of furosemide are modified by prior administration of nonsteroidal anti-inflammatory drugs. Furosemide administration attenuates exercise-induced increases in right atrial, aortic, and pulmonary artery pressures in ponies. Furosemide prevents exercise and allergen-induced bronchoconstriction in humans and decreases total pulmonary resistance in ponies with recurrent obstructive airway disease. These pharmacologic effects are frequently used to rationalize its questionable efficacy in the prevention of exercise-induced pulmonary hemorrhage. Neither the effect of furosemide on athletic performance nor its efficacy in the prevention of exercise-induced pulmonary hemorrhage has been convincingly demonstrated.

Animals↗

PubMed1997

Urinary excretion of endogenous ouabain-like substance in furosemide-treated neonates: its relation to renal excretory pattern and endocrine factors.

The present study was undertaken to define the possible role of endogenous ouabain-like substance (EOLS) in controlling renal excretory pattern, in mediating the renal responses to furosemide and in inducing endocrine reactions in furosemide-treated neonates. Ten newborn infants with mean birthweight of 2,752 g and mean gestational age of 37.1 weeks were given furosemide in a dose of 1 mg/kg. Prior to and following furosemide therapy, urine was collected for a period of 12 h and analyzed for creatinine, osmolality, sodium and potassium, as well as for EOLS, arginine vasopressin (AVP), aldosterone and endothelin-1 (ET-1). In response to furosemide administration, urine flow rate and urinary osmolar, sodium and potassium excretion increased significantly, whereas creatinine excretion remained unchanged. Furthermore, following furosemide therapy, urinary excretion of EOLS (148.7 +/- 70.8 vs. 200.1 +/- 98.1 pg/kg/h) and AVP (19.5 +/- 5.4 vs. 27.8 +/- 7.8 pg/kg/h) tended to increase, whereas ET-1 (36.0 +/- 5.6 vs. 61.4 +/- 8.7 fmol/kg/h, p < 0.01) and aldosterone (507 +/- 120 vs. 751 +/- 203 ng/kg/h, p < 0.05) increased significantly. Prior to furosemide, urinary EOLS excretion was found to correlate positively with diuresis (r = 0.80, p < 0.01), sodium (r = 0.91, p < 0.001), creatinine (r = 0.75, p < 0.001), osmolar (r = 0.96, p < 0.001), ET-1 (r = 0.90, p < 0.001) and AVP (r = 0.92, p < 0.001) excretion. After furosemide, urinary EOLS excretion significantly correlated only with diuresis (r = 0.69, p < 0.05), ET-1 (r = 0.77, p < 0.01) and AVP (r = 0.92, p < 0.001). Urinary EOLS proved to be independent of aldosterone excretion irrespective of furosemide administration. It is concluded that urinary EOLS excretion is closely related to neonatal renal excretory pattern and it may have a role in controlling diuresis and natriuresis. The renal response to furosemide appears to be independent of EOLS, although interdependent endocrine reactions can be induced by furosemide which may modulate the production rate and urinary excretion of EOLS.

Aldosterone↗

PubMed2003

20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension.

Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126+/-24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio. UNaV by furosemide was less in SS (263+/-25 mmol/12 hours) than in SR (351+/-25 mmol/12 hours, P<0.02) patients. 20-HETE was not different between SS and SR patients before (1.92+/-0.38 versus 1.37+/-0.34 microg/h) or after furosemide (1.52+/-0.27 versus 2.01+/-0.40 microg/h), but furosemide changed 20-HETE excretion in opposite direction in SR (0.63+/-0.26) versus SS (-0.40+/-0.17, P<0.005) patients. In all patients together, %Delta20-HETE by furosemide correlated with %DeltaUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Delta20-HETE by furosemide correlated with Deltaaldosterone/renin ratio (r=0.60, P<0.05), whereas 20-HETE during furosemide had a negative correlation with body mass index (r=-0.73, P<0.01). Our data suggest that 20-HETE modulates the natriuretic response to furosemide, and impaired natriuresis of SS involves a mechanism that alters the 20-HETE response to furosemide and is linked to salt-sensitivity of blood pressure.

Adult↗

PubMed2006

Effect of lecithin coating on the pulmonary absorption of furosemide in rats.

The effect of lecithin coating on the pulmonary absorption of furosemide after application by metered dose inhalers (MDI) containing HFA 227 was evaluated in rats. The plasma concentration of furosemide after application of lecithin-coated furosemide was higher than that after application of the un-coated form. Since the disposition in the lung 2 min after application of un-coated furosemide was significantly lower than that after application of the coated form and the adsorption to a polyethylene tube used for the application of the un-coated form was significantly higher than that of the coated form, the higher plasma concentration after application of lecithin-coated furosemide could be partly related to the efficient delivery of the furosemide particles to the lung. The permeation-enhancing effect of the lecithin coating was investigated using Calu-3 cell monolayers. The cumulative amount of furosemide permeated over 2 h from a suspension containing lecithin-coated furosemide through the monolayers was significantly higher than that from a conventional furosemide suspension. This enhancing effect could also contribute to the high plasma concentration of furosemide in rats. The lecithin-coated furosemide will be useful for the formulation of MDI offering high bioavailability.

Animals↗

PubMed1990

Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I).

Furosemide (frusemide) is a potent loop diuretic used in the treatment of oedematous states associated with cardiac, renal and hepatic failure, and for the treatment of hypertension. Therapy is frequently complicated by apparently erratic systemic availability from the oral route and from unpredictable responses to a given dosage. The exact mechanism of action is not fully understood, but furosemide is believed to act at the luminal surface of the ascending limb of the loop of Henle by inhibiting the active reabsorption of chloride. The response to a given dosage is modulated by the fluid and electrolyte balance of the individual. Acute and delayed tolerance has been demonstrated both in animals and in man, and is postulated to be due to the intervention of homeostatic mechanisms influencing fluid and electrolyte balances. Furosemide is delivered to its site of action by active secretion via the nonspecific organic acid pump. Comparisons between the observed diuresis/saluresis and plasma furosemide concentrations, urinary excretion rates and renal clearance found either negative or no correlations with plasma drug concentration but significant correlations with urine measurements. Response is related to the concentration of the drug in urine rather than in plasma. The most common adverse reactions attributable to furosemide therapy are essentially extensions of the therapeutic effects (i.e. fluid and electrolyte disturbances). The pharmacokinetic behaviour of furosemide is marked by a large degree of variability, derived from differences within and between both subjects and study protocols. Part of this variability can be attributed to differences in organ function, which is important in view of the types of patients treated with furosemide. On the other hand, a large proportion remains as inter- and intrasubject variation. The bioavailability of furosemide from oral dosage forms is highly variable. The poor bioavailability has been hypothesized to be due to the poor solubility of the compound, site-specific absorption, presystemic metabolism and/or other unknown mechanisms. Furosemide is highly bound to plasma proteins, almost exclusively to albumin. Although the drug is insoluble in water and favours partitioning into fatty tissue, the high degree of plasma protein binding restricts the apparent volume of distribution at steady-state to values within a multiple of 2 to 5 times the plasma volume. Furosemide has two documented metabolites--furosemide glucuronide and saluamine (CSA). The first is an accepted metabolic product, whereas the status of CSA as a metabolite is highly controversial.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Kidney Injury↗

PubMed1979

Acetylsalicyclic acid restores acute insulin response reduced by furosemide in man.

Prostaglandin E (PGE) infusion in normal man inhibits the acute insulin response to glucose. In order to determine whether endogenously released PGE might also inhibit insulin secretion, glucose-stimulated insulin responses were investigated in normal volunteers after furosemide (40 mg i.v.), a stimulator of endogenous PGE synthesis. Acute insulin response to glucose (20 g i.v.) was significantly reduced by furosemide (response before furosemide: 36 +/- 5 muU/ml; after furosemide: 26 +/- 5 muU/ml, m +/- SE, mean change 3--10 min, N = 8, P less than 0.01), whereas glucose disappearance rates were not modified after furosemide. Infusion of lysine acetylsalicylate (LAS), an inhibitor of endogenous PGE synthesis, completely reversed the inhibitory effect of furosemide on insulin secretion and also augmented acute insulin response to glucose (response before furosemide + LAS: 41 +/- 6 muU/ml; during furosemide + LAS: 50 +/- 7 muU/ml, N = 10, P less than 0.02). This effect was associated with an increase in glucose disappearance rates (P less than 0.05). These findings demonstrate that (1) furosemide inhibits glucose-induced acute insulin responses and (2) LAS completely reverses the inhibitory effect of furosemide and also accelerates glucose disposal. It is suggested that furosemide acts via the release of endogenous PGEs, which are known to inhibit insulin responses in man.

Adult↗

PubMed1995

Furosemide reduces the incidence of pulmonary hypertension syndrome (ascites) in broilers exposed to cool environmental temperatures.

The incidence of pulmonary hypertension syndrome (PHS; ascites) was evaluated in two experiments using broiler breeder male by-product chicks exposed after 3 wk of age to cool environmental temperatures (10 to 15 C). In Experiment 1, 3- to 6-wk-old birds were fed a grower diet to which 0 (Control), .001, .005, .010, or .015% furosemide had been added. All groups in Experiment 1 were fed a finisher ration containing no furosemide during Weeks 7 to 8. In Experiment 2, the Control group received no furosemide, a second group received .015% furosemide during the grower phase only (Weeks 3 to 6), and the third group received .015% furosemide during the grower and finisher phases (Weeks 3 to 8). Cumulative PHS mortality was significantly reduced by furosemide in both experiments. Compared with Controls, birds fed .015% furosemide did not have lower (P = .077) final body weights in Experiment 1 but did have significantly lower final body weights in Experiment 2. Lower levels of furosemide significantly reduced PHS mortality without reducing body weights. Furosemide did not improve feed conversion in either experiment. Neither body weight on Day 1 or 21 nor net Day 1 to 21 weight gain were predictive of susceptibility to PHS during the subsequent grower and finisher intervals in either experiment. On Day 55 of Experiment 2, large healthy birds fed .015% furosemide had significantly lower right:total ventricular weight ratios than control birds, indicating that furosemide reduced right ventricular hypertrophy, presumably by reducing pulmonary arterial pressure.

Animals↗

PubMed2000

Effects of the V(2)-receptor antagonist OPC-41061 and the loop diuretic furosemide alone and in combination in rats.

This study was conducted to characterize the diuretic effect of OPC-41061, a nonpeptide vasopressin V(2)-receptor antagonist, and furosemide by administering each alone and in combination in conscious male rats. OPC-41061 at 1 and 10 mg/kg and furosemide at 10 and 100 mg/kg dose-dependently increased urine volume to the same extent. The high dose of OPC-41061 (10 mg/kg) markedly elevated electrolyte-free water clearance (E-CH(2)o) to a positive value. In contrast to OPC-41061, furosemide elevated only electrolyte clearance but not E-CH(2)o. The differences in diuretic profile reflected the changes in serum sodium and hormone levels. OPC-41061 dose-dependently elevated serum sodium concentration, but furosemide tended to decrease it. The high dose of furosemide (100 mg/kg) significantly elevated serum renin activity and aldosterone concentration, indicating that furosemide activated the renin-angiotensin-aldosterone system (RAA-system). On the other hand, OPC-41061 did not affect these parameters. When OPC-41061 was administered concomitantly with furosemide, OPC-41061 significantly increased urine volume and E-CH(2)o, and decreased urinary osmolality compared with furosemide alone. OPC-41061 dose-dependently elevated serum osmolality and sodium concentration even when administered in combination with the high dose of furosemide. These results suggest that OPC-41061 produces aquaresis leading to increased serum sodium without affecting the RAA-system. On the other hand, furosemide produced natriuresis, leading to decreased serum sodium level and activation of the RAA-system. It was also demonstrated that OPC-41061 produced an additive diuretic effect and elevated serum sodium level in the presence of furosemide.

Aldosterone↗

PubMed1992

Influence of furosemide on hemodynamic responses during exercise in horses.

Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only RAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.

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