Effect Of Diuresis Research Articles

The Effects of Diuresis on the Pharmacokinetics of the Loop Diuretics Furosemide and Torsemide in Patients with Heart Failure

Purpose: To evaluate the pharmacokinetics of furosemide and torsemide before and after diuresis in patients presenting with marked fluid overload. Subjects and Methods: We studied 44 patients with New York Heart Association class III or IV heart failure, ejection fraction ≤40%, and an estimated excess fluid body weight ≥6.8 kg. Oral furosemide or torsemide was administered before and after diuresis. Pharmacokinetic parameters were assessed before and after diuresis. Results: Following diuresis, maximum plasma concentration increased from 11.0 ± 5.0 μg/mL to 13.9 ± 6.8 with torsemide ( P <0.05) and from 3.1 ± 1.5 to 3.9 ± 1.9 with furosemide ( P = 0.16). Maximum concentration increased by more than 30% in only one third of the patients. Total absorption (by area under the curve method) increased 6% among patients on torsemide ( P = 0.38) and 7% among patients on furosemide ( P = 0.63) and increased >30% in only 1 torsemide and 2 furosemide patients. The time to maximum concentration decreased from 1.40 ± .82 h to 0.81 ± 0.36 with torsemide ( P <0.01). There were no differences between furosemide and torsemide in the effects of edema on absorption. Conclusion: Marked diuresis altered the pharmacokinetics of both furosemide and torsemide in only a small percentage of patients. The use of adequate doses of oral diuretics in edematous patients may be successful, thereby permitting home treatment with oral diuretics and avoiding the cost of hospitalizations or home intravenous administration services.

Combination of long-acting furosemide and instant-acting amiloride: pharmacokinetics and pharmacodynamics in human subjects

The pharmacokinetics and pharmacodynamics of the combination of amiloride (2 x 2.5 mg) and long-acting furosemide (2 x 10 mg) were compared with amiloride (5 mg) and furosemide (20 mg) in 12 healthy male volunteers aged 26.2 +/- 1.6 years and weighing 68.8 +/- 6.2 kg, after random order administration. Furosemide and amiloride plasma or urine concentrations were determined by HPLC with fluorimetric detection. The rate of absorption (tmax = 3 h) and the bioavailability of the two diuretics were not significantly modified by their combination. Furosemide plasma half-life was 2.77 +/- 1.04 h after the combination treatment and 2.76 +/- 0.98 h alone, amiloride plasma half-life was respectively 15.7 +/- 4.6 h and 14.6 +/- 3.7 h. The urinary elimination of furosemide was significantly higher in the 2-4 h interval in the combination treatment, accompanying its delayed maximum effect of diuresis. A synergistic effect was observed after the combination administration of the two diuretics; between the 2nd and the 8th hour, the sodium elimination was significantly increased (P less than 0.01) and the potassium excretion was significantly decreased (P = 0.05). After a single dose, no modification of plasma or erythrocyte magnesium levels was observed. This study shows that the combination of the two drugs entails a synergy of their activities which does not involve pharmacokinetic changes.

Plasma osmolality, iodine concentration and urographic images following high and low osmolar contrast media

Three contrast media (sodium iothalamate, iopamidol and sodium/methylglucamine ioxaglate) in a dose of 240 mg iodine per kilogram of body weight were compared in clinical urography. The ionic monomer sodium iothalamate was the only medium to significantly elevate the plasma osmolality though it returned to normal values within 4 min. All three media exhibited first order linear kinetics. When corrected for the effects of diuresis, sodium iothalamate was shown to give the highest urinary iodine concentrations. On visual scoring sodium iothalamate produced better nephrograms and overall urograms than either of the low osmolar agents.

The effects of diuresis and transfusion on pulmonary function in children with thalassemia major

Previous pulmonary function studies in subjects with thalassemia major (TM) who were on regular transfusion programs have demonstrated results ranging from small airway obstruction to a restrictive pattern. Ten subjects with TM were studied pre- and postdiuresis, and again 24 hr after transfusion, in order to evaluate the role of possible fluid overload in altering pulmonary function. Subjects underwent spirometry and had lung volume and flow volume curves (MEFVC) measured in a volume displacement plethysmograph while breathing air and a mixture of 80% helium and 20% oxygen (HeO2). Six patients had pulmonary mechanics measured with esophageal balloons in place. Baseline function was normal and no change occurred following diuresis. Following transfusion, the volume of isoflow (VisoV) decreased, but other parameters did not change. Subsequent analysis revealed 5 subjects with an initial VisoV greater than 20 (% FVC) but, paradoxically, less evidence of flow limitation in the small airways than those with a VisoV less than 20 (% FVC). Posttransfusion, in those subjects with an initially high VisoV, the Vmax25(air) tended to fall without a change of MEFVC in HeO2, resulting in a decreased VisoV. This was interpreted as evidence of subtle abnormalities in the small airways caused by volume expansion, raising doubts about the value of the VisoV as a measure of small airway disease. As a group, our subjects did not demonstrate any abnormalities in baseline function. Some subjects had mild flow limitation in small airway while other developed comparable levels of flow limitation following the volume expansion associated with transfusion.

Active and Inactive Urinary Kallikrein in Man: Effects of Diuresis and Antidiuresis

1. The urinary excretion of active and inactive kallikrein was studied in volunteers during diuresis induced by water loading or oral frusemide and during antidiuresis induced by desamino-D-arginine-vasopressin. 2. During acute oral water loading, excretion of active kallikrein was unchanged, despite high urine flow rates and low urine osmolalities being achieved. Excretion of inactive kallikrein correlated with the urine flow rate. 3. After desamino-D-arginine-vasopressin in eight water-loaded and six normally hydrated subjects, excretion of inactive kallikrein also correlated with the urine flow rate. There were no significant changes in the excretion of active kallikrein. 4. After frusemide there was a small transient increase in excretion of active kallikrein 1-2 h after dosing which coincided with the maximum diuresis and natriuresis. Excretion of inactive kallikrein again correlated with urine flow rate but the regression relationship between the two variables was different for water-load-induced and frusemide-induced diuresis. 5. These studies do not support a role for urinary kallikrein in the modulation of the antidiuretic action of vasopressin, but suggest that it may contribute to the natriuretic action of frusemide.

Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure

purpose: The pleural fluid that accumulates secondary to congestive heart failure is almost always a transudate based upon its level of protein and lactic acid dehydrogenase (LDH). Previous work has suggested that the characteristics of the fluid may change into those of an exudate with diuresis. The purpose of the present study was to determine whether aggressive diuresis does result in this change in pleural fluid characteristics. patients and methods: Twelve patients with severe congestive heart failure (ejection fraction 23.9 ± 9.6%) and pleural effusions were studied serially as they underwent diuresis. After an initial thoracentesis was performed, the patients then underwent aggressive diuresis for 12 to 48 hours with one or two follow-up thoracenteses. results: The mean weight loss during the study period was 4.5 ± 2.8 kg. With diuresis the LDH level, LDH ratio, protein level, and protein ratio all increased significantly (p <0.05). All 12 patients had transudative pleural effusions at the onset of diuresis. However, despite the increases in the levels of protein and LDH with diuresis, only one patient's pleural fluid attained values compatible with an exudate. conclusion: From this study we conclude that it is uncommon for a transudative pleural effusion due to congestive heart failure to develop the characteristics of an exudative pleural effusion with rapid diuresis.

Effect of diuresis on the oxalate excretion and the calcium-oxalate product in non-stone formers.

We studied the effect of variations of fluid intake on the oxalate (Ox) excretion in healthy subjects. The relation of Ox excretion to urine volume was examined. The Ca excretion was measured as well and the ionized Ca and the Ca X Ox product were calculated. With a fluid intake between 800 and 4,200 ml a urine volume between 550 and 4,200 ml was found. We saw a strong correlation between urine volume and Ox excretion and a strong negative correlation between urine volume and urinary Ox concentration. The upper limit of urinary Ox excretion to define hyperoxaluria should therefore be modified by taking the urine volume into consideration or should be replaced by the Ox concentration.

The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man.

To substantiate the effects of urine flow rate on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase (NAG) excretion, experiments were performed in normal human subjects. Urine flow rate was varied by overnight fluid deprivation and progressive diuresis induced by oral water loading. Lysozyme measurements were made using an improved turbidimetric method and NAG determinations using a modified fluorometric assay utilising individual recovery techniques. Fractional lysozyme clearance and lysozyme excretion demonstrated a nearly linear relationship with urine flow rate (r = 0.78, r = 0.80, P less than 0.0005), and both were elevated significantly in samples obtained during diuresis. NAG excretion, however, demonstrated a significant but weak correlation (r = 0.47, P less than 0.005) with fractional urine flow rate. A significant (P less than 0.05) difference in NAG activity occurred only during the period of hydropenia, when a decrease in excretion was observed. These findings suggest that the effect of diuresis on lysozyme excretion should be considered in studies utilising this enzyme as a marker of renal injury.

Different diuresis-dependent excretions of urinary enzymes: N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, alkaline phosphatase, and gamma-glutamyltransferase.

We studied how much of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) and of the brush-border enzymes alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), and gamma-glutamyltransferase (EC 2.3.2.2) was excreted in urine over 8 h after a high intake of fluid (22 mL per kilogram of body weight). The hourly excretion of all four enzymes increased with the increasing urine flow rate. The excretion rate of the brush-border enzymes was more markedly influenced than that of N-acetyl-beta-D-glucosaminidase. By relating the enzyme excretion to urinary creatinine we could reduce the variability of brush-border enzyme output and could completely compensate for the effect of diuresis on the excretion of N-acetyl-beta-D-glucosaminidase.

Effects of Furosemide Diuresis on Mercuric Chloride-Induced Acute Renal Failure in the Rat

In previous studies in rats given mercuric chloride (HgCl2), administration of furosemide has been found to either attenuate, exacerbate, or not affect the severity of the acute renal failure (ARF) otherwise expected to obtain. In the current study in rats given large doses of furosemide and in which urinary fluid losses were replaced by intravenous infusions of saline, administration of HgCl2 induced less severe ARF than that induced in rats not given furosemide and saline infusions. In rats not given furosemide, a diuresis induced by continuous reinfusion of urine also conferred protection against the nephrotoxic effect of HgCl2. These findings suggest that in rats given HgCl2: diuresis per se is the critical determinant of any salutary effect of furosemide and the protective effect of diuresis does not depend on renal elimination of mercury.

Effect of Diuresis and Glucagon on Upper Urinary Tract Dynamics in the Dog

The effect of glucagon on upper urinary tract peristalsis during extreme diuresis was studied in an unsedated dog preparation. In all experiments glucagon inhibited the peristaltic contraction waves without affecting urine propulsion, suggesting that peristalsis, at least for short periods, is not necessary for effective urine transport during extreme diuresis.

Evaluation of Obstructive Uropathy With Diuretic Renography

• Diuretic renography has been recommended as a useful test to distinguish obstructed from dilated, but not obstructed, urinary systems. Twenty-four diuretic renograms were performed in 20 children, and a good correlation was found with other indicators of obstruction. The sensitivity for identifying obstruction was 83%, with a specificity of 94%. Severe hydroureteronephrosis may blunt or even mask the effect of diuresis on causing emptying of the tracer from the renal pelvis. Some kidneys did not drain well with the patient in a supine position but did empty with a change of position; these kidneys should be regarded as nonobstructed. ( Am J Dis Child 1983;137:236-240)

Effect of diuresis on the performance of the failing left ventricle in man : Wilson JR, Reichek N, Dunkman WB, Goldberg S: Am J Med 1981; 70: 234–239

Effect of diuresis on the performance of the failing left ventricle in man : Wilson JR, Reichek N, Dunkman WB, Goldberg S: Am J Med 1981; 70: 234–239

Studies on the derivatives of aminoalcohols. V. Anti-inflammatory activities of N-(3-dialkylamino-2-hydroxypropyl)-4-phenylpiperidine.dihydrochloride (author's transl)

In order to develope a non-steroidal anti-inflammatory drug, N-(3-dialkylamino-2-hydroxypropyl)-4-phenylpiperidine·2HCl was synthesized. Five compounds were examined for anti-inflammatory effects on swelling of rat hind paw induced by dextran and on mice scald oedema, diuresis effects, depression effects of normal body temperature. In general, the order of anti-inflammatory effects of these compounds was IIIe>IIId>IIIb>IIIc>IIIa. The inhibition percentage of scald oedema of compound No. IIId, e were higher than that of cortisone acetate and aspirin. These compounds had scarcely diuresis action. The order of depression effects on normal body temperature was IIIc>aminopyrine>IIIe≒IIId>IIIb>IIIa.

Biliary and urinary excretion of drug conjugates: Effect of diuresis and choleresis on excretion of harmol sulphate and harmol glucuronide in the rat

1. Harmol (7-hydroxy-1-methyl-9H-pyrido [3,4b] indole) is converted to harmol sulphate and harmol glucuronide in the rat in vivo. Harmol sulphate is excreted mainly in urine, while harmol glucuronide is excreted about equally in bile and urine, when harmol is given intravenously. 2. In rats with ligated kidneys, only choleresis produced by glycodehydrocholate and dehydrocholate caused enhanced biliary excretion of harmol sulphate; harmol glucuronide was unaffected. Several other bile salts had no effect. 3. Mannitol diuresis markedly increased urinary excretion of harmol sulphate, and decreased its biliary excretion. Harmol glucuronide was much less affected. 4. Nafenopin pretreatment increased liver weight and bile flow, and enhanced biliary excretion of harmol sulphate at the expense of its urinary excretion. 5. For harmol sulphate, urine and bile are compensatory pathways of elimination that can be influenced by urine and bile flow changes through diuresis and choleresis.

Effect of diuresis and nephron dimensional heterogeneity on the distribution of nephron filtration rates

Conflicting data in studies of the effect of natriuresis on intrarenal single nephron glomerular filtration rate (SNGFR) redistribution may arise from the interplay of hitherto largely overlooked factors. In the present work, the effect of diuresis induced by saline, glucose or mannitol, as well as the effect of anatomical nephron heterogeneity, were studied. A highly significant positive correlation was found between the logarithm of the urine flow per gram of kidney weight (log V) and the mean superficial (S) to mean juxtamedullary (JM) SNGFR ratio. The rise in S/JM SNGFR with diuresis was primarily a function of decreased JM SNGFR. Total proximal tubular length (TPL) was used as a measure of nephron size. The distribution of nephron sizes was evaluated as S/JM TPL. The effects of urine flow and anatomical heterogeneity on S/JM SNGFR were spearated by means of multiple regression analysis, which yielded the following equation: S/JM SNGFR = -0.049 + 0.179 log V + 0.818 S/JM TPL. Both slopes were highly significant (P less than 0.001). These findings indicate that S/JM SNGFR increases with urine flow, independently of sodium homeostasis, and that anatomical heterogeneity has a marked effect and must, therefore, be controlled. Conflicting data in the literature are harmonized with the present data when appropriate correction can be made for the dimensional factor. There is no evidence that SNGFR redistributions play a role in sodium homeostasis.

Augmentation of urinary amylase output by excessive diuresis in rats and abolition of this phenomenon by pancreatectomy

Effects of diuresis on urinary amylase output were observed in control and pancreatectomized rats on the administration of tap water, glucose and amino acid solution. (1) Urine volume and urinary amylase output were increased as the concentration of glucose solution was increased. Amylase output in the urine revealed a positive correlation with the urine volume. (2) Augmentation of urinary amylase output was also observed in diuretic rats produced by the administration of amino acid solution. (3) Augmentation of urinary amylase output was not found in pancreatectomized rats, although the urine volume was more pronouncedly increased compared to control rats. (4) The urinary amylsae output revealed a positive correlation with the ratio of amylase clearance to creatinine clearance by the kidney in control rats, while the output remained unchanged over relatively wide range of the ratio in pancreatectomized rats. Above evidences indicated that urinary amylase output was significantly augmented by excessive diuresis and that the increased urinary amylase output originated from the pancreas

Simulated vesicoureteral reflux: comparison between the normal and hydrostatically bypassed ureterovesical junction as a function of urine flow rate and bladder pressure.

The effects of diuresis on the function of the ureterovesical junction have been comparatively examined in the normal and hydrostatically bypassed ureters. Electromyography of the ureter and renal pelvic pressures were simultaneously monitored with elevations of bladder pressure. It is shown that under oliguric conditions the bypassed ureter reflects bladder pressures to the renal pelvis, while the control ureter and the renal pelvis is hydrostatically isolated from the bladder. Under polyuric conditions the control and bypassed ureters respond identically.

Hemodynamic effects of diuresis by ethacrynic acid in normal subjects and in patients with congestive heart failure.

Hemodynamic effects of intravenous administration of ethacrynic acid, 1 or 2 mg/kg, were studied in five normal subjects and in five patients with advanced congestive heart failure. In normal subjects, the diuresis averaged 1.2 liters in 90 minutes, resulting in a reduction in plasma volume of 14%. Stroke index fell by a mean of 21%, arteriovenous oxygen difference widened by 13%, and orthostatic tolerance was decreased. Patients in congestive heart failure showed a mean diuresis of 1.8 liters and a decrease in plasma volume of 9%. Central venous pressure fell from a mean of 16 to 10 mm Hg. Cardiac index increased by 18% from a mean of 1.8 liters/min/sq m, and stroke index rose by 11%. The arteriovenous oxygen difference narrowed from 8 to 7.1 vol%. Orthostatic stress was tolerated well.

Further cinefluorographic observations on the upper urinary tract. II. The effects of diuresis and ureteral obstruction.

Study of the physiology of the renal pelvis and the ureter has been hampered by the relative inaccessibility of these structures. Frequently examinations have been performed with instruments and equipment which, by the very nature of their construction or method of application, yielded results rendered invalid through artefact production. Although at present several methods for the study of renal pelvic and ureteral function yield acceptable and reproducible results, (3, 5, 9–11) only radiography permits direct observation of undisturbed structures under consideration. A previous publication has shown that cinefluorography is a satisfactory technic for visualizing the dynamic changes which occur in the normal upper urinary tract (1). At that time, it was pointed out that the activity of the upper urinary tract could be divided into two patterns: that of the bifid renal pelvis, in which the contractions originate in the upper infundibulum and that of the ampullary renal pelvis in which the contractions originate in the pelvis proper. The purpose of this paper is to extend these observations by studying the effects of both diuresis and ureteral obstruction on the motor function of the upper urinary tract. Method A total of 25 cinefluorographic studies were undertaken in 25 patients. Of these, 21 were suitable for analysis and inclusion in this study. The 21 patients were free from significant urinary tract disease, and intravenous urographic examinations were essentially normal. The patients were divided into two separate groups, a diuresis group numbering 12 and an obstruction group of 9. A. The Diuresis Group: All patients in the diuresis group received a preliminary intravenous injection of 25–30 cc of Renografin-60 or Renovist, after which cinefluorography of the upper urinary tract was carried out in a fashion previously described (1). The ciné runs were long enough to include several peristaltic complexes. At this point, an intravenous infusion of 150 cc of Renovist was instituted and the entire contents were infused in a period of ten to fifteen minutes, in an attempt to take advantage of the well known osmotic diuretic properties of concentrated urographic contrast media. At the end of the infusion, cinefluorography was once again performed. In some cases, hypertonic mannitol was infused, in addition to the urographic contrast medium, but this resulted in considerable dilution and impaired opacification of the renal collecting system. The use of mannitol was discontinued because its effects were simulated by the contrast medium alone. B. The Ureteral Obstruction Group: The patients in the ureteral obstruction group also received 25–30 cc of Renografin-60 or Renovist, following which cinefluorography was performed.