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PubMed1984

Clinical investigations on the pharmacology of azosemide (SK-110) in comparison with furosemide in healthy volunteers.

In this study, 60 mg of Azosemide and 40 mg of Furosemide were each administered to 2 volunteer persons. The daily urine volume after administration of both drugs was almost the same. Azosemide didn't show such rapid diuretic effect as was seen in Furosemide, but Azosemide proved to have a mild diuretic and protracted effect as compared with Furosemide. The influence on a daily urinary and fecal excretion of electrolyte and the decrease of serum electrolytes proved to be the same in administration of either drug. However, in the case of Furosemide, most of the electrolytes were excreted within 3 hours after administration, while Azosemide showed mild and prolonged excretion. The effect of both drugs on serum uric acid was almost the same showing a slightly rising trend.

Adult↗
PubMed1978

Effects of ozolinone, a diuretic active metabolite of etozoline, on renal function. I. Clearance studies in dogs.

The renal action of 3-methyl-4-oxo-5-piperidino-thiazolidine-2-ylidine (ozolinone), a metabolite of the diuretic etozoline (Elkapin), was studied in anaesthetized dogs after i.v. injection and compared with the renal effects of furosemide. The diuretic action of ozolinone was rapid in onset and of short duration. The smallest effective i.v. dose was 1 mg . kg-1. Maximal diuretic capacity was reached at 50 mg . kg-1 i.v. Fractional tubular sodium reabsorption was depressed to 67% at maximal effective doses. Ozolinone had similar renal actions to those of furosemide. Like furosemide, ozolinone increased renal blood flow, slightly decreased glomerular filtration rate, depressed tubular chloride reabsorption more than sodium reabsorption, increased potassium excretion, lowered the pH of urine, decreased urinary osmolarity towards isotonicity and depressed tubular PAH secretion. As regards the effective doses and the maximal changes of tubular sodium excretion, ozolinone was somewhat less potent than furosemide.

Animals↗
PubMed2001

Furosemide-probenecid interaction as a laboratory exercise for undergraduate education in clinical pharmacology.

OBJECTIVE: The aim of this study was to determine the easiness, reproducibility, and safety of a laboratory exercise for a drug interaction between furosemide and probenecid. METHODS: From 1995 to 1999 approximately 100 medical students participated in the exercise each year after they gave written informed consent. The students were randomly assigned to one of the three groups in a double-blind fashion: group 1, placebo plus 20 mg of furosemide; group 2, 250 mg of probenecid plus 20 mg of furosemide; and group 3, 1000 mg of probenecid plus 20 mg of furosemide. The students took probenecid or its placebo 1 hour before furosemide. Urine volume and urinary sodium excretion were measured for 3 hours after furosemide. At the end of the exercise in 1999, students responded to several questionnaires concerning the utility of furosemide. RESULTS: The entire course of the exercise was completed within half a day. The following findings were obtained every year. (1) Probenecid dose dependently blunted the diuretic effects of furosemide. (2) Time courses of the diuretic effects were altered by probenecid. Ten to twenty percent of the students had slight complaints but completed the exercise without any medications. Finally, more than 80% of the students considered the exercise to be useful. CONCLUSIONS: The data suggest that the exercise of the drug interaction between furosemide and probenecid is easy to perform, reproducible, and safe. Through the experience of the laboratory exercise, students will develop an attitude to assess and estimate potential drug interactions before they prescribe drugs.

Diuresis↗
PubMed1993

Does Aerua lanata have diuretic properties?

We have compared the diuretic activity of 200 ml of sucrose flavoured aqueous extract of the herb Aerua lanata with that of 200 ml sucrose flavoured weak infusion of tea leaves, and 200 ml of water, in 14 healthy volunteers under standardized conditions. Each volunteer acted as his or her own control in the three protocols, and chemical, physical and statistical analyses were performed "blind" by coding all urine and blood samples collected. A. lanata extract did not significantly increase urine flow, sodium excretion, potassium excretion, or urine and plasma osmolality as compared to an infusion of tea or plain water.

Adult↗
PubMed2003

Effects of forced diuresis achieved by oral hydration and oral diuretic administration on uroflowmetric parameters and clinical waiting time of patients with lower urinary tract symptoms.

INTRODUCTION: We studied the impact of diuresis forced by oral hydration or single-dose oral diuretic administration on uroflowmetric parameters and clinical waiting time of patients with lower urinary tract symptoms. PATIENTS AND METHODS: A total of 58 patients with a mean age of 59 (range 41-77) years who presented with lower urinary tract symptoms were included in the study. The patients were grouped with respect to their International Prostate Symptom Scores as having mild, moderate, or severe symptoms. The prostatic volumes of the patients were calculated using transrectal ultrasound. Uroflowmetric measurements were performed on 3 consecutive days. On the 1st day, the test was performed without diuretic stimulation; on the 2nd day, oral hydration was applied, and on the 3rd day, the patients received 20 mg of furosemide orally. Voiding time, maximum flow rate, voided volume, and the time elapsed in minutes until voiding (waiting time) were recorded. RESULTS: Diuretic stimulation did not significantly alter the uroflowmetric parameters in each symptom group, but the waiting time was significantly reduced. Forced diuresis caused acute urinary retention in 5 of 20 (25%) severely symptomatic patients. CONCLUSIONS: Forced diuresis with oral hydration or oral administration of diuretics improves patient comfort and test applicability by shortening clinical waiting time and reducing the number of attempts to reach the sufficient urine volume for reliable measurements and can be applied safely for mild and moderately symptomatic patients. On the other hand, the risk of 25% of acute urinary retentions should be reconsidered, and the decision about diuretic stimuli should be made carefully by the clinician in severely symptomatic patients.

Administration, Oral↗
PubMed1984

Effect of captopril on intrarenal blood flow.

The inhibition of the renin-angiotensin system by captopril was used in pentobarbital-anesthetized dogs to confirm that the vasoconstrictive action of endorenally synthesized angiotensin II predominates on the efferent glomerular arteriole. Ozolinone is a loop diuretic with two isomers. Only (-)- ozolinone is diuretic, whereas both isomers have a renal vasodilatory effect which predominates on the efferent glomerular arteriole. Only the diuretic isomer increases renin release. The renin hypersecretion is simultaneous with recovery from the initial fall in filtration fraction, because of postglomerular vasodilatation. This recovery does not occur with (+)- ozolinone and is inhibited by pretreatment with captopril. This confirms that vasoconstrictive action of angiotensin II predominates on the efferent glomerular arteriole. Such a vasoconstrictive effect might affect blood flow in the vasa recta, which arise from the efferent arterioles of juxtamedullary glomeruli. This action might enable the renin-angiotensin system to participate in the control of renal medullary blood flow and urinary concentration.

Animals↗
PubMed1996

Segmental reabsorption measured by micropuncture and clearance methods during hypertonic sodium infusion in the rat.

BACKGROUND: We wanted to validate by direct measurements in rat tubules a technique used to calculate segmental volume absorption by each segment of the human nephron. METHODS: Experiments were performed on 17 rats during hypertonic Na infusion prior to and after frusemide administration. Tubular samples were taken from early distal and last proximal sites. The rate of filtration of single nephrons (SNGFR) was calculated by the technique of total collection of tubular fluid using labelled inulin as a marker. Reabsorption was computed by the tubular fluid to plasma (TF/P) inulin concentration ratio. RESULTS: SNGFR was 50 +/- 4 nl/min at the distal (n = 82), 51 +/- 3 nl/min at the proximal sampling site (n = 112, P > 0.65) during baseline conditions. Percent reabsorptions were 85 +/- 1 and 69 +/- 2% respectively (P < 0.0001). During frusemide these values were 52 +/- 6 nl/min and 76 +/- 2% at the distal, 49 +/- 5 nl/min and 66 +/- 2% at the proximal site. In 83 paired proximal collections, fractional (68 +/- 1 versus 67 +/- 1% P > 0.32), absolute reabsorption (34 +/- 2 versus 33 +/- 2, P > 0.50) and SNGFR (50 +/- 2 nl/min versus 50 +/- 3 nl/min, P > 0.99) were not different between baseline and frusemide. In 25 re-collections from the distal tubule these same values were 83 +/- 2% versus 76 +/- 2%, and 48 +/- 4 nl/min versus 55 +/- 6 nl/min respectively. Very similar results were obtained in 55 paired distal-proximal collections during baseline and 42 such pairs during frusemide. In the presence of the diuretic the fractional urine excretion was significantly correlated (R = 0.83, P < 0.0001) with fractional proximal delivery, Na+ resorption by Henle's loop was 22 +/- 2% calculated from clearance data and 23 +/- 1% of GFR from micropuncture data respectively. They were not significantly different (P > 0.70) and were significantly correlated (R = 0.57, P < 0.02). CONCLUSIONS: These data demonstrate that frusemide does not act proximally and that delivery beyond the proximal tubule approximates urine flow rate during the action of the drug. The values of segmental reabsorption along the nephron computed on clearance measurements are superimposable upon those obtained directly by micropuncture.

Animals↗
PubMed1995

Diuretic and antidiuretic effects of mesotocin as compared with the antidiuretic effect of arginine vasotocin in the hen.

Mesotocin and arginine vasotocin were injected intravenously once at various dosage levels (.0025 to 25 micrograms/kg body weight) immediately after an intravenous injection of 15 mL/kg body weight saline solution into hens in which an artificial anus had been surgically created, and the volume of urine excreted during a 5-h period, following the injection, was measured. Arginine vasotocin caused a monophasic, dose-dependent decrease in urine volume. By contrast, mesotocin was biphasic: at .025 and .25 micrograms/kg body weight it decreased urine volume with the same efficacy as arginine vasotocin, whereas it dramatically increased urine volume at the higher doses (2.5 and 25 micrograms/kg body weight).

Animals↗
PubMed1983

Preclinical studies of indapamide, a new 2-methylindoline antihypertensive diuretic.

Indapamide is a new indoline antihypertensive diuretic agent whose chemical structure differs substantially from those of the thiazides. The hydrophobic indoline moiety of indapamide confers a lipid solubility to the molecule that is 5 to 80 times greater than that of the thiazide diuretics. Thus indapamide accumulates in vascular smooth muscle at a concentration 10 times higher than that of protein-free perfusate. The affinity of indapamide for vascular smooth muscle manifests itself in vitro and in vivo as a decrease in reactivity following various pharmacologic interventions. Moreover, in vitro studies have demonstrated that indapamide decreases the inward calcium current and the transmembrane influx of calcium. The diuretic effect of indapamide is predominantly due to inhibition of sodium reabsorption at the cortical diluting segment of the distal convoluted tubule. In animal studies, intravenous indapamide has no effect on glomerular filtration rate or renal blood flow. Indapamide is well absorbed and extensively metabolized in animals and humans, with biliary excretion being the predominant route of elimination in animals. Most important, repeat administration of indapamide to dogs with both kidneys removed produces no accumulation of intact indapamide or its metabolites. Extensive drug safety studies in animals indicate that indapamide produces no overt toxicity and exhibits a good margin of safety.

Animals↗
PubMed2003

Primary Sjögren's syndrome associated with Gitelman's syndrome presenting with muscular paralysis.

A 38-year-old woman presented with muscle cramping of 4 extremities and paralysis for months. Laboratory results showed an elevated antinuclear antibody titer; antibodies to the ribonucleoprotein antigen Ro; hypokalemia; hypomagnesemia with hyperreninemia, but abnormally high urine potassium and magnesium levels and low urine calcium levels; and a blunted diuretic effect to thiazide, but not furosemide, which met the criteria for Gitelman's syndrome (GS) and led to the diagnosis of primary Sjögren's syndrome (pSS). She received medical treatment, including a potassium supplement and aldosterone antagonist. GS as a presentation of pSS has never been reported in the literature. The features of renal diseases related to SS are reviewed. SS is the underlying cause of GS, which may precede the onset of the well-known sicca complex.

Adult↗
PubMed1975

[The saluretic effect of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylilide) in normal subjects].

The diuretic and saluretic effectiveness of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor) is determined and compared to those of chlortalidone and furosemid in normal subjects. The substance is revealed as a potent diuretic agent. In the range of 0.035--0.750 mg/kg body weight the dose-response curve of orally administered xipamide for the increase of excretion of urine, sodium and potassium ion and chloride during 24 h is described. Observing the renal activity over a period of 3 days after a single administration the duration of action is found to be up to 24 h with its maximum within the first 12 h. In the following 2 days the degree of the physiological rebound effect depends on the preceding saluretic effect and thus on the given dose. The pattern of ion-excretion (Na

Administration, Oral↗
PubMed2000

Synthesis and diuretic activity of bicyclic fused heterocycles containing oxime-O-sulfonic acid moiety.

In order to investigate the origin of the loop-type diuretic activity of M17055 (1), several variants (3-9) were designed and synthesized by modifying the quinolinone skeleton, and their diuretic activities were compared with the lead 1 and furosemide in dogs. It was found that the negative charge distribution pattern afforded by the dispositional arrangement of the 4-oxime-O-sulfonic acid and 1-N-acyl carbonyl moiety attached to the tetrahydropyridine ring system is inevitable for the development of the activity, which strongly supports the previously proposed model for the active site of the Na(+)-K(+)-2Cl(-) cotransporter. Also reported is the first synthesis of the dihydrothieno[3,2-b]pyridine-7(4H)-one ring system required in the synthesis of compound 9.

Animals↗
PubMed1976

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids.

A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.

Acetates↗
PubMed1977

(Acylaryloxy)acetic acid diuretics. 1. (2-Alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids.

The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocyclic parent compound, lacked the double bond adjacent to the carbonyl group. More importantly, they possessed both saluretic and uricosuric properties. The optimal single 2-substituents for maximal saluretic and uricosuric activity were determined. In general, better activity was observed when a second 2-alkyl substituent (especially methyl) was present in the molecule. Replacement of the carboxy substituent by 5-tetrazolyl generally resulted in a reduction in activity.

Acetates↗
PubMed1997

Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats.

BACKGROUND: That non-natriuretic doses of loop diuretics exert an antihypertensive action has been suggested, but not confirmed, by simultaneous measurements of the arterial pressure and sodium balance during therapy. OBJECTIVE: To examine the relationship between changes in arterial pressure and changes in sodium balance during furosemide treatment. DESIGN: Twenty hypertensive Dahl salt-sensitive rats fed a 4% NaCl diet were allocated to four groups and administered the following treatments: placebo once a day intraperitoneally, continuous infusion of 4 mg/day furosemide intraperitoneally, 4 mg furosemide once a day intraperitoneally and 12 mg furosemide once every third day intraperitoneally. METHODS: The mean arterial pressure (MAP) was measured continuously with radiotelemetry and the sodium balance was measured with the rats in metabolic cages. RESULTS: Administration of furosemide as a bolus injection once a day (P < 0.01) or once every third day (P < 0.05) lowered the MAP significantly compared with placebo, whereas continuous infusion of furosemide had no significant effect on the MAP (P < 0.07). Fast Fourier transformation analysis detected an acute antihypertensive action related to the temporary diuretic and natriuretic responses during the period 0-6 h after intraperitoneal bolus injections of 4 and 12 mg furosemide. None of the treatment regimens produced 24 h sodium or potassium losses. At the end of the study, the total body water, extracellular fluid volume, total body sodium and potassium were similar for rats in all groups. CONCLUSIONS: Furosemide has an acute antihypertensive action in Dahl salt-sensitive rats fed a 4% NaCl diet that is related to renal sodium and volume losses whereas the long-term antihypertensive effect is independent of changes in extracellular fluid volume, total body water, sodium and potassium.

Animals↗
PubMed1996

Effect of water deprivation for 48 hours on the pharmacokinetics and pharmacodynamics of azosemide in rats.

The effect of temporary water deprivation for 48 h on the pharmacokinetics and pharmacodynamics of azosemide was examined after intravenous (i.v., 10 mg/kg) and oral (20 mg/kg) administration of azosemide to the control and the water-deprived rats. After i.v. administration of azosemide, the area under the plasma concentration-time curve from time 0 to time infinity and the unbound fraction of azosemide to plasma proteins increased by 36 and 40%, respectively, and total body, renal (CLR), and nonrenal clearances, apparent volume of distribution at steady state, and total amount of azosemide excreted in urine (AeAZ0) decreased by 30, 44, 20, 25, and 33%, respectively, in the water-deprived rats (p < 0.05 vs controls). After oral administration of azosemide, the values of AeAZ0 (591 vs 318 micrograms) and CLR (2.22 vs 0.875 mL/min/kg) decreased significantly in the water-deprived rats. The 12-h urine output per g kidney was also reduced significantly in the water-deprived rats after both i.v. (70.3 vs 24.6 mL) and oral (70.7 and 20.7 mL) administration of azosemide. This could be due to the significantly reduced amount of azosemide excreted in 12 h urine, significantly higher plasma osmolarity, and increased blood vasopressin concentration in the water-deprived rats. The 12-h urinary excretion of sodium, potassium, and chloride per g kidney was also reduced significantly in the water-deprived rats after both i.v. and oral administration. The diuretic efficiency decreased significantly in the water-deprived rats after both i.v. and oral administration. The 12-h urine output per g kidney of i.v. and oral administration of azosemide in the control rats were similar (70.3 +/- 17.3 vs 70.7 +/- 13.8 mL), although the AeAZ0 after oral administration was significantly smaller than that after i.v. administration (473 +/- 98.5 vs 285 +/- 76.3 micrograms), and similar results were also obtained from the water-deprived rats. This could be rationalized by the concept of a single maximally efficient excretion rate of the drug in the pharmacodynamic model (sigmoid Emax), as shown for furosemide.

Animals↗
PubMed1983

[Effects of several beta-blockers and penfluzide, a thiazide diuretic, on the blood pressure, urinary water output and excretion of Na and K in DOCA-saline-induced hypertension in rats].

Effects of beta-blockers on the blood pressure (BP), urinary output (V) and excretion of Na% (UNaV) and K+ (UKV) were studied in DOCA-saline hypertensive rats in comparison with those of a thiazide diuretic drug, penfluzide. Pindolol produced a hypotension at all infusion rates of Ringer's solution used and a decrease in V with a retention of Na+ and K+ at a low infusion rate. There was a parallel shift of Guyton's renal function curve back to the lower pressure ranges. Similar effects were observed with labetalol. Propranolol induced an increase in UKV at all infusion rates and had a diuretic action at a high infusion rate without producing a significant fall of BP. UKV tended to be increased after atenolol, with essentially no change in other parameters. A new beta-blocker with alpha-blocking action, K-351, produced a hypotension at intermediate and high infusion rates and an increase in UNaV (low infusion rate) and UKV (low and high rates). UKV tended to be increased with another new beta-blocker, N-696, with a fall of BP at high infusion rate. Penfluzide produced a significant decrease in BP at intermediate and high infusion rates and an increase in UKV at all infusion rates.

Adrenergic beta-Antagonists↗
PubMed1994

The saluretic effect of the thiazide diuretic bemetizide in relation to the glomerular filtration rate.

The effect of the thiazide diuretic, bemetizide, on the excretion of Na+, K+, Cl-, Ca2+, and Mg2+ in relation to the glomerular filtration rate (GFR) was studied in 17 subjects whose creatinine clearances ranged from 133 to 5 ml.min-1. After a 2-day fluid and salt balanced control period, 25 mg bemetizide given orally induced natriuresis and kaliuresis which lasted for 24 h and were proportional to the GFR of the patients. The ratio of bemetizide-induced K+/Na+ excretion was always 0.17 irrespective of individual GFR. In renal failure, bemetizide increased the fractional Na+ excretion from 3% to about 10%. Kaliuresis was associated with magnesiuria, whereas bemetizide-induced calciuresis was insignificant. The thiazide reversibly lowered GFR in all subjects.

Adult↗