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Effects of indomethacin on furosemide induced renal prostaglandin synthesis and action in man.

We had previously shown that the early increment in plasma renin activity occurring within ten minutes of intravenous furosemide is accompanied by an increase in urine 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) the hydrolysis product of prostacyclin. Renal prostacyclin and thromboxane A2 synthesis are apparently limited to the cortex. To assess whether indomethacin would inhibit renal cortical eicosanoid synthesis and whether such reduction correlated with reduced early renin release, we assessed responses to intravenous furosemide (0.5 mg/kg) before and after indomethacin (150 mg/day for seven days) in ten normal male volunteers. Indomethacin did not change blood pressure but increased weight slightly (79.7 +/- 2.5 kg to 80.4 +/- 2.4 kg, p less than 0.05). Serum thromboxane B2 (TXB2), a measure of platelet thromboxane A2 production, was profoundly depressed (142 +/- 29 ng/ml to 4.8 +/- 1.6 ng/ml, p less than 0.001). Neither diuresis nor natriuresis were changed by indomethacin but potassium excretion was reduced (33 +/- 4 mmol/4 hr to 27 +/- 3 mmol/4 hr, p less than 0.05). Basal as well as furosemide stimulated plasma renin activity (at 10, 30 and 240 minutes) was reduced, as well as the transient increase in excretion rates of 6-keto-PGF1 alpha and TXB2. We conclude that the reduction in furosemide stimulated renin release by indomethacin is due to renal cyclo-oxygenase inhibition which is reflected in decreased excretion rates of hydrolysis products of renal eicosanoids.

6-Ketoprostaglandin F1 alpha↗

Udder edema in cattle: effect of furosemide, hydrochlorothiazide, acetazolamide, or 50% dextrose on venous blood pressure.

Before injection of diuretic drugs, blood pressures were determined in the cranial superficial epigastric veins (milk vein) and jugular veins of 15 Holstein cows with udder edema at parturition and of 15 healthy (control) cows at parturition. Cows with udder edema had a significant (P less than or equal to 0.05) mean increase in cranial superficial epigastric venous pressure at parturition, compared with that of control cows. After IV administration of 500 mg of furosemide in cows with udder edema, the mean cranial superficial epigastric venous blood pressure significantly (P less than or equal to 0.05) decreased within 5 minutes, remained at the decreased pressure for 90 minutes, and then returned to near pretreatment pressures by 210 minutes after furosemide injection; however, furosemide did not significantly affect the jugular venous blood pressure of these cows. Furosemide injection did not significantly affect the cranial superficial epigastric or jugular venous blood pressure in the control cows. After IV administration of hydrochlorothiazide (250 mg), acetazolamide (500 mg), or 50% dextrose (500 g), the cranial superficial epigastric and jugular venous blood pressures in cows with udder edema at parturition were not significantly different from those in cows without udder edema at parturition during the 210-minute evaluation period after injection of the drugs.

Acetazolamide↗

Effect of furosemide administration on systemic circulation of ponies during severe exercise.

Systemic distribution of blood flow was studied in 11 healthy adult grade ponies, using radionuclide-labeled microspheres (15 micron diameter) that were injected into the left ventricle. Measurements were made at rest, during severe exercise (SE) without furosemide, as well as during SE at 10 minutes and 120 minutes after furosemide administration (1.0 mg/kg, IV). During SE, heart rate, cardiac output, mean aortic pressure, and whole body O2 consumption were 220 +/- 4 beats/min, 720 +/- 44 ml/min/kg, 169 +/- 4 mm of Hg, and 126 +/- 9 ml of O2/min/kg, respectively. With SE performed after furosemide administration, mean aortic pressure decreased from prefurosemide SE value (P less than 0.05), but heart rate, cardiac output, and whole body O2 consumption remained similar to values during SE without furosemide. During SE, blood flow to cerebellar gray matter, pons, and medulla oblongata increased despite marked hypocapnia, but in other regions of the brain, blood flow was unchanged. As arterial O2 content increased by 58% with SE, O2 delivery to all brain regions increased. With SE, adrenal gland blood flow increased, but intense vasoconstriction in the kidneys, spleen, pancreas, small intestine, and colon caused blood flow to plummet. During SE, blood flow in the diaphragm, gluteus medius, biceps femoris (muscles of propulsion), and triceps brachii muscles increased to a similar level, indicating that metabolic requirements of the diaphragm during exercise may not be less than those of other vigorously contracting muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Antihypertensive comparison of furosemide with hydrochlorothiazide for black patients.

Furosemide and hydrochlorothiazide were compared for treatment of black patients with mild to moderate hypertension in a randomized, open-label, crossover study design. Hydrochlorothiazide produced a significantly greater fall in mean arterial (24.7 vs 16.0 mm Hg, P less than .01) and diastolic (17.3 vs 10.1 mm Hg, P less than .01) blood pressure (BP) in 16 patients. Addition of methyldopa in nine patients produced a significantly greater fall in mean arterial (38.8 vs 31.9 mm Hg, P less than .05) and diastolic (28.9 vs 23.4 mm Hg, P less than .05) BP with hydrochlorothiazide vs furosemide. Renin status was categorized before and after treatment. Patients with low and normal renin activity were equally responsive to both diuretics. Hydrochlorothiazide caused a greater reduction in plasma potassium (0.26 mEg/L). Serum parathyroid hormone was not chronically elevated with furosemide. In this study, hydrochlorothiazide was more effective than furosemide for treatment of mild to moderate hypertension in black patients; renin classification did not predict diuretic responsiveness.

Adult↗

Comparative pharmacodynamics of furosemide and muzolimine in cirrhosis. Study on renal sodium and potassium handling and renin-aldosterone axis.

Ten male cirrhotic patients with ascites and reduced renal function were randomly given equivalent doses of furosemide and muzolimine by the oral route, through a single blind cross-over protocol. Renal function, electrolyte plasma concentrations and urinary excretions and renin-angiotensin-aldosterone system components were evaluated under basal conditions and after drug administration. The diuretic and saluretic effects being equal, the response to muzolimine was initially weaker but more prolonged than to furosemide, without rebound phenomena. The furosemide-induced natriuresis was in part related to the filtered sodium load, whereas muzolimine natriuresis was only correlated to the inhibition of tubular sodium reabsorption. No potassium wasting effect was seen after muzolimine administration. Transient plasma potassium concentration reduction observed during muzolimine suggests an ion shift within the intracellular compartment. Therefore, a possible interaction of the drug with cellular sodium active transport systems can be hypothesized. A significant increase of plasma renin activity was observed after furosemide. No significant changes were seen after muzolimine administration.

Angiotensin II↗

Pressures in the right side of the heart and esophagus (pleura) in ponies during exercise before and after furosemide administration.

Pressures in the right side of the heart and esophagus (pleural) have not been determined in the exercising equine subjects. In the present study, 8 healthy ponies were examined to determine the changes in these variables caused by 2 degrees of exercise done on a treadmill (heart rate:183 +/- 5 beats/min [trot] and 220 +/- 6 beats/min [canter]). Measurements were also made during both degrees of exertion 10 minutes and 120 minutes after furosemide (1.0 mg/kg) administration. It was observed that both gaits resulted in significant increases in pulmonary artery, right ventricular, and right atrial pressures. The pulmonary artery systolic, mean, and diastolic pressures during strenuous exertion were 306%, 252%, and 242% of the respective resting values. At canter, when respiratory frequency (138 +/- 4 breaths/min) is synchronized with stride frequency, the delta esophageal pressure approached 30.4 +/- 2.86 cm of water. During exercise 10 minutes after furosemide administration, the increment in right atrial pressure was markedly attenuated. During strenuous exertion 120 minutes after furosemide administration, the right atrial and pulmonary arterial pressures increased, but to a significantly lower level than did the prefurosemide values. However, the mean pulmonary artery pressure was still 240% of the resting value. It is concluded that marked pulmonary hypertension is a consistent feature of moderate, as well as strenuous, exertion in the pony. Although furosemide administration attenuated the pulmonary hypertension somewhat, the significance remains unclear.

Animals↗

Effect of furosemide on the clinical course of transient tachypnea of the newborn.

The effect of furosemide on the course of transient tachypnea of the newborn was evaluated in a controlled, prospective study. Fifty infants with transient tachypnea of the newborn were randomly assigned to control or treatment groups. Those in the treatment group were given furosemide, 2 mg/kg orally, at the time of diagnosis followed by 1 mg/kg 12 hours later if the symptoms persisted. Infants in the control group received a placebo. Compared with infants in the control group, the furosemide-treated group demonstrated no significant difference in the duration of tachypnea nor in the length of hospitalization. It is concluded that oral furosemide, at the doses used in this study, does not significantly affect the clinical course of transient tachypnea of the newborn.

Female↗

Effects of furosemide on the racing times of horses with exercise-induced pulmonary hemorrhage.

In 3 groups of horses with exercise-induced pulmonary hemorrhage (EIPH), comparisons of racing times and finishing positions were made between the 5 races before the horses were given furosemide and 5 races after furosemide administration. The horses were grouped according to 3 methods used to diagnose EIPH: group 1, observation of hemorrhage at the nostrils within 1 hour after a workout or race; group 2, observation of pulmonary hemorrhage only by endoscopic examination after a race or workout; and group 3, observation of hemorrhage at the nostrils during a race or immediately after a race. Group 4 horses were randomly selected horses running during the study period and were not given furosemide. The statistical method was analysis of covariance and the dependent variable was horses' time per distance. The study compared the 4 groups of horses, using the estimated value of the horses (less than or equal to +10,000 or greater than +10,000), and the horses' interaction in races 1 through 5 before and races 6 through 10 after furosemide treatment. The horses' times were adjusted by the relevant covariates, distance, track variant, and winning time per distance. Significant changes in horses' time per distance were not noticed when comparing values from races 1 through 5 with those in races 6 through 10 in group 1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Efficacy of furosemide in the treatment of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses.

The repeatability of endoscopic observations of exercise-induced pulmonary hemorrhage (EIPH) and the efficacy of furosemide as a prophylactic treatment of horses with EIPH were studied in Thoroughbred race horses after consecutive breezes (at or near maximum speed, approx 16 m/s). Of 56 horses examined greater than or equal to 2 times, 21 (38%) had identical EIPH scores, whereas 26 (46%) and 9 (16%) had scores that differed by greater than or equal to 1 grade. In 56 nontreated horses, there was good agreement between 2 consecutive observations (K = 0.59, Z = 4.54, P less than 0.001). Similar comparisons after placebo (saline solution) treatment of 21 horses yielded fair to good agreement, whereas poorer agreement was seen after furosemide treatment of 23 horses. Comparison of average and maximum EIPH scores of 44 horses with a minimum of 4 observations (2 nontreated, 1 saline-treated, and 1 furosemide-treated) indicated that although furosemide did not stop EIPH, it did reduce the EIPH score in 28 (64%) horses.

Animals↗

[Studies on the diuretic effects of etozolin (Elkapin) in heart failure - a comparison with the loop diuretic agent furosemide (author's transl)].

UNLABELLED: In 115 randomized patients with left and/or right ventricular failure, the effect of the new diuretic Etozolin (800 mg p.o.) (n = 55) is compared with that of the loop diuretic Furosemide (80 mg p.o.) (n = 60). RESULTS: 1. The increased diuresis after Etozolin remains constant during the entire trial period. Furosemid initially induces a more intense diuresis. 2. Analysis of the action profile shows that the higher daily urinary output following Furosemide is due to a more intense diuresis in the first fractions of the day. The action of Etozolin is more constant and lasts into the evening. 3. Both substances reduce body weight to the same extent. 4. Heart rate and arterial blood pressure decline significantly during trial. 5. Etozolin induces lesser electrolyte elimination than Furosemide in the initial phase of the trial. Potassium elimination values, in particular, remain below Na+ and Cl- elimination values for both substances. 6. During the trial period both substances had no significant effect on blood and liver values, serum electrolytes, creatinine, urea and uric acid. Etozolin may be classified as a diuretic similar to a thiazide derivative in its 24-h profile but behaves like a loop diuretic in its diuretic effect.

Blood Cell Count↗

The effects of long-term oral treatment with chlorothiazide or furosemide on hereditary diabetes insipidus in rats.

The polyuria of homozygous Brattleboro (BB) female rats is halved when they are given chlorothiazide (about 250 mg/day) or furosemide (about 60 mg/day) orally for one day. The effect of chlorothiazide is still found after 16 days of treatment, whereas the effect of furosemide entirely disappears within 5 days. Both diuretics induce chronically increased plasma renin activity (PRA) and decreased natriuresis as long as they are added to the diet; the effect on Na is more evident during furosemide treatment. Urinary urea content as well as urinary osmolality are increased by chlorothiazide and "free water" output is normalized. Furosemide does not affect urea content and decreases urinary osmolality from the start, as compared to untreated BB homozygotes; it raises "free water" output above BB values.

Animals↗

Decrease in hepatic blood flow during furosemide-induced diuresis.

The effect of furosemide on hepatic hemodynamics was investigated using electromagnetic flow probes positioned around the hepatic-portal vein and common hepatic artery of anesthetized dogs. Furosemide administration induced a vigorous diuresis and concomitantly decreased total hepatic blood flow. Hepatic arterial blood remained relatively stable. Thus, the decrease in total hepatic blood flow was due primarily to a decrease in portal blood flow. When furosemide was given to animals with ureters ligated to prevent extracellular volume contraction, the drug did not reduce total hepatic blood flow, portal blood flow or hepatic arterial blood flow. Thus, furosemide induces a decrease in total hepatic blood flow that appears to involve a mechanism dependent upon the volume contraction produced by the diuretic. The contraction causes a reduction in venous blood flow but not arterial blood flow to the liver.

Animals↗

[Hemodynamic consequences of the furosemide treatment of cardiac insufficiency in recent myocardial infarct].

Furosemide was administered intravenously to 11 patients with cardiac failure after acute myocardial infarction. After an initial loading dose furosemide was given four-hourly if the pulmonary capillary wedge pressure (PCW) was not normalized, i.e. less than or equal to 15 mm Hg. The comparison of the hemodynamic results with the results of a previous study with nitrates was as follows: like the nitrates furosemide lowered the PCW early, i.e. within 15 minutes from 22 +/- 3 to 18 +/- 5 mm Hg, but the therapeutic objective (PCW less than or equal to 15 mm Hg) was reached later than with nitrates. During the 24-hour observation period PCW and total peripheral resistance decreased steadily. The decrease of cardiac index to critical low values in some patients after a mean of 7.5 hours of therapy, and of the mean arterial pressure from 100 +/- 13 to 91 +/- 14 mm Hg, may limit the use of furosemide alone in these patients. During nitrate therapy PCW started to rise again after 12 hours in some patients, necessitating higher doses of nitrates with a corresponding decrease of diuresis. A combination of both forms of therapy may be of value and needs further investigation.

Aged↗

[Furosemide in newborns infants with idiopathic respiratory insufficiency syndrome].

Due to the interstitial pulmonary edema present in neonates with idiopatic respiratory distress syndrome (IRDS), it was believed furosemide would be useful in its treatment. In newborns with this syndrome, the effect of said diuretic was studied in blood gases, oxygen alveoloarterial difference and right to left short circuit. Twenty-two infants with similar clinical and laboratory characteristics were included in the study. Out of them, 11 were given furosemide (1 mg/kg/single dosis) and the remaining cases were controls. No difference was shown between both groups in PaO2 and PaCO2 and therefore, the alveoloarterial difference of oxygen nor the right to left short circuit during 60 minutes that the study lasted were either affected even if the infants who were given furosemide showed a significantly greater urinary flow. Due to the above results, the use of furosemide is not recommended for children with IRDS to eliminate an interstitial edema.

Carbon Dioxide↗

Effects of MK-196 and furosemide on rat medullary thick ascending limbs of Henle in vitro.

The effects of the diuretic agents, MK-196 (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy acetic acid) and furosemide on function of medullary thick ascending limb (tALH) isolated from the rat kidney were studied. tALH were dissected from whole kidneys of male Sprague-Dawley rats which were first perfused in vitro in a recirculating system for 10 to 15 min with a solution containing collagenase. Standard techniques for dissection and perfusion of tALH were followed. Control transepithelial voltage averaged +5.5 +/- 0.5 mV (n = 25). Drug concentration causing 50% inhibition of the voltage (EC50) was determined. EC50 for both MK-196 and furosemide in rat tALH was 8 X 10(-6) M (EC50 for MK-196 in rabbit tALH ws 7 X 10(-5) M). In other experiments, net chloride transport (JCl) in rat tALH averaged 142 +/- 19 pmol.mm-1.min-1 (n = 12), a value nearly twice that reported for the rabbit. In the rat, MK-196 (2 X 10(-4) M) reduced the voltage by 79 +/- 2% and JCl by 76 +/- 13% (n = 6). The same concentration of furosemide inhibited the voltage by 78 +/- 8% and the JCl by 104 +/- 4%(n = 5). Results indicate that: 1) rat tALHs dissected from collagenase-treated kidneys have functional characteristics similar to those reported for the rabbit tALH; and 2) the rat tALH is equally sensitive to MK-196 and furosemide, drugs which act to selectively inhibit active chloride transport.

Animals↗

Hormonal response to acute diuresis--a comparative study of furosemide and azosemide.

We observed and compared the hormonal response to acute diuresis for 6 hours by orally administered furosemide 40 mg and azosemide 60 mg in normal male volunteers. The treatment resulted in significant urine volume increase with its peak during 1 to 2 and 2 to 3 hours after administration, and the 6-hour cumulative urine volume was 2488 +/- 163 ml in furosemide and 2930 +/- 109 ml in azosemide, respectively. The plasma noradrenalin concentration rose with the increase of urinary noradrenalin excretion, but plasma adrenalin remained unchanged in spite of its increased excretion. Serum aldosterone and plasma renin activity rose with resultant increase of urinary aldosterone excretion. Such a stimulation of the renin-angiotensin-aldosterone system was greater with azosemide than with furosemide. Plasma ADH and serum prolactin concentration was also increased. As compared with the furosemide responses, 1 to 2 hour delayed responses were observed in urinary adrenalin and noradrenalin, plasma renin activity, serum and urinary aldosterone, plasma ADH and serum prolactin. This was probably caused by delayed onset of the diuretic action in the case of azosemide. The findings suggested that the differences in the hormonal responses of the two drugs are mainly explained by the difference in their diuretic phase.

Adult↗

[Pharmacokinetics and electrolyte balance following administration of furosemide in pregnant women with E gestosis].

In pregnant women with E-gestosis distribution and elimination of furosemid are significantly different to a non-pregnant control group. Furosemid guarantees a rapid and safe excretion of edemas. The efficiency of furosemid concerning electrolyte excretion is stronger in pregnant women with E-gestosis than in nonpregnant women. Therefore furosemide should be administered to pregnant women under intensive electrolyte control only.

Calcium↗

Pharmacokinetic and pharmacodynamic effects of furosemide in patients with impaired renal function.

Three groups of patients with kidney diseases were investigated: I. creatinine in serum less than 100 mumol/l, II. creatinine in serum 100-250 mumol/l, III. creatinine in serum greater than 250 mumol/l. After intravenous injection of 40 mg and 80 mg furosemide, serum concentrations and urinary excretion of the unchanged drug were measured fluorometrically. Moreover, urinary excretion of water, electrolytes, creatinine and urea nitrogen were estimated in order to check the pharmacodynamic effect of the drug. The pharmacokinetic parameters calculated were similar in group I and II. In group III t 1/2 was prolonged, renal clearance of furosemide was diminished. The diuretic effect of furosemide was noticeable during the first 4 hours following the injection of 40 mg in all 3 groups. Doubling the dose did not enhance the effect. Creatinine and urea nitrogen excretion in urine were not influenced by furosemide.

Creatinine↗