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PubMed2005

Attenuation of the kaluretic properties of furosemide by triamterene (Dyrenium) in healthy volunteers.

OBJECTIVE: To examine if concomitant administration of furosemide, a loop diuretic, with the potassium- and magnesium-sparing diuretic triamterene would decrease loss of potassium and magnesium while improving diuresis. METHODS: In this open-label, three-way crossover study, healthy subjects were randomized to receive treatment with 40 mg furosemide, with 150 mg triamterene, or treatment with 40 mg furosemide and 150 mg triamterene. Urine samples were collected 24 hours before dosing and between 0 - 1, 1 - 2, 2 - 3, 3 - 4, 4 - 6, 6 - 8, 8 - 12, and 12 - 24 hours post-dosing. Sodium and potassium levels were measured by an ion-selective electrode method. Magnesium was measured colorimetrically using a xylidyl blue reaction. RESULTS: Co-administration of furosemide with triamterene resulted in enhanced diuresis, particularly in the first 0 - 12 hours post-dose, compared with either furosemide or triamterene alone. Compared to individual treatments, combination therapy significantly increased urinary sodium excretion (p = 0.0001) while significantly decreasing urinary potassium excretion (p = 0.0001); importantly, the magnesium-sparing characteristic of triamterene was retained with furosemide co-administration. CONCLUSION: Triamterene, when used in combination with the loop diuretic, furosemide, preserves intracellular potassium and magnesium while enhancing the natriuretic effect of furosemide.

Adolescent↗
PubMed1991

Pharmacodynamic and kinetic considerations on diuretics as a basis for differential therapy.

Diuretics are classified according to their site of action in the nephron: loop diuretics, thiazides, and antikaliuretics. During peak diuresis the pattern of electrolyte excretion is constant and characteristic for a class of diuretics. The ratio of diuretic-induced excretion of K+ to Na+ is 0.12 for loop diuretics, 0.20 for thiazides, and -0.21 for antikaliuretics. The ratio of Ca2+ to Na+ is 0.02 for loop diuretics and 0.003 for thiazides. Mg2+ excretion follows K+ excretion in a ratio of 0.15. The natriuretic effect of a diuretic directly depends on the renal clearance of the drug and is proportionate to the number of intact nephrons. Not only loop diuretics but also thiazides and antikaliuretics were demonstrated to be effective natriuretic drugs down to end-stage renal disease. In renal failure FENa is doubled with every halfening of GFR. Loop diuretics increase FENa to a maximum of 24%, thiazides to 10-15%, and FENa is doubled by antikaliuretics. Comedication of loop diuretics with thiazides in renal failure may therefore be more effective than increasing monotherapy. In liver disease, nonrenal drug clearance is reduced the more the patient's direct bilirubin rises thus causing an increase in AUC and urinary excretion of parent drug and metabolites. Despite increased Ae, the cirrhotic patient may become resistant to diuretics as many patients with congestive heart failure or nephrotic syndrome. This is considered to be due to reduced Na+ load available at the diuretic's site of action following avid proximal Na+ reabsorption. In reduced EABV a short-term comedication of loop diuretics with carboanhydratase inhibitors is considered a more effective diuretic strategy than vigorously increasing monotherapy.

Biotransformation↗
PubMed1968

4-Leucine-oxytocin: natriuretic, diuretic, and antivasopressin polypeptide.

During water diuresis in anesthetized rats, 4-leucine-oxytocin increased the urine output and the rates of sodium and chloride excretion. The potassium excretion rate was only slightly increased. During vasopressin-suppressed water diuresis, 4-leucine-oxytocin produced similar effects on urine and electrolyte excretions. In addition, it inhibited the vasopressin-induced free-water reabsorption, and it could reverse reabsorption to freewater clearance.

Absorption↗
PubMed2005

Diuresis renal scintigraphy "F-0" in diagnosing of upper urinary tract obstruction in children: the clinical significance.

BACKGROUND: The aim of this study was to assess the clinical relevance of diuresis renal scintigraphy after simultaneously administered radiopharmaceutical and diuretic (DRS "F-0") in diagnosing obstruction of upper urinary tract in children with previously documented hydronephrosis and ureterohydronephrosis, analyzing the value of qualitative and quantitative scintigraphy parameters. MATERIAL AND METHODS: This retrospective study enrolled 82 children (30 girls and 52 boys aged between 2 months and 16 years; mean 5.8 +/- 4.5 years) with previously documented hydronephrosis or ureterohydronephrosis (42 left-sided, 28 right-sided and 12 bilateral). DRS "F-0" was started after intravenous administration of diethylene-triamine- pentaacetic acid (DTPA) mixed with furosemide. Results of DRS "F-0" were analyzed qualitatively (visual analysis of scintigrams and renography curves) and quantitatively (time to reach maximum of the kidney curve-T max, washout of the tracer-WO, the furosemide clearance half-time (F/2) and individual kidney function - IKF) and compared with the final diagnoses obtained in 37 children (42 nephroureteric units - NU) after surgery, in 41 children (48 NU) during the medical follow-up lasting at least 6 months, and in 4 children (4 NU) using invasive diagnostic procedures. Diagnostic criteria for obstructed NU (kidney with corresponding ureter) considered presence of pathological at least two of five scintigraphy variables characterized as a sign of obstruction. RESULTS: Forty true positive and 37 true negative results were detected using diagnostic criteria for obstructed and normal NU by means of DRS "F-0". DRS "F-0" failed to detect obstruction in 5 children with a total of 6 obstructed NU, while the results were marked as false positive in 9 children (11 NU). Qualitative scintigraphy analysis was found to be the most sensitive (91%) and accurate predictor (85%) in differentiating obstruction from non-obstructive renal unit. High sensitivity in predicting obstruction was also found for both washout of the radiopharmaceutical (87%) and for furosemide clearance half time (85%). Overall sensitivity of DRS "F-0" using proposed diagnostic criteria in differentiating obstruction was 87%, specificity 77% and accuracy 82%. However, DRS "F-0" has been shown to be more sensitive (90%) in children with UPJ and UVJ obstruction concerning children in whom obstruction was caused by other urinary tract diseases. CONCLUSION: This study showed DRS "F-0" as a sensitive and reliable method in diagnosing children with obstructions of the upper urinary tract. The great advantage of the protocol DRS "F-0" over other diuresis renography protocol modalities is due to the shorter time of the acquisition by half, and the avoidance of additional diuretic application. However, conventional quantitation of diuresis renogram did not improve the sensitivity and specificity with respect to the qualitative analysis of scintigrams and renography curves.

Adolescent↗
PubMed1995

The role of continuous infusion loop diuretics.

OBJECTIVE: To evaluate the role of continuous infusion loop diuretics in selected patient populations, discuss the advantages and disadvantages associated with continuous infusion, and recommend monitoring parameters for the use of continuous infusion therapy. Current dosing guidelines for continuous infusion loop diuretics have not been established, but a summary of previously studied doses is provided. DATA SOURCES: A literature search using MEDLINE, International Pharmaceutical Abstracts, as well as additional references found in pertinent articles. STUDY SELECTION AND DATA EXTRACTION: Clinical studies concerning the use of loop diuretics administered by continuous infusion were evaluated in selected patient populations. All articles and clinical studies were considered for possible inclusion in the review. Information judged to be pertinent by the authors was selected for discussion. DATA SYNTHESIS: Comparative studies in the congestive heart failure (CHF), renal-insufficient, and postcardiac surgery patient populations have shown that loop diuretics administered by continuous infusion are more beneficial than those given by intermittent bolus administration. In adult patients with CHF, furosemide 3-4 mg/h is recommended. In adult and pediatric postcardiac surgery patients, furosemide dosages of 0.05 and 0.1 mg/kg/h have produced diuresis. In patients with renal insufficiency, bumetanide 0.912 mg/h has produced diuresis. Intravenous bolus doses were used in all studies reviewed except 1. These studies have indicated that continuous infusion of the loop diuretics yields diuresis without increasing toxicity. CONCLUSIONS: The use of continuous infusion loop diuretics is a therapeutic alternative for patients requiring diuresis. This form of administration has provided more consistent urine flow, fewer alterations in fluid balances, fewer urinary losses of electrolytes as well as decreased dosage of the diuretic requirements. The disadvantages have not been fully elucidated because of the limited evaluation of this administration method. Few studies have used this method of administration; however, the few data available indicate that continuous infusion of loop diuretics is an efficacious alternative to conventional therapy.

Diuretics↗
PubMed1979

Hypothalamic temperature and osmoregulation in the Pekin duck.

The temperature of the anterior and middle hypothalamus of conscious Pekin ducks was altered with chronically implanted thermodes. Both urine formation and salt secretion by the supraorbital glands were influenced by hypothalamic cooling. When osmotic diuresis was induced by continuous intravenous infusion of 1.2 ml . min-1 of 293 mosm . kg-1 mannitol in H2O solution, hypothalamic cooling increased urine flow rate at reduced urine osmolality and unchanged osmolal excretion rate. The degree of this cold induced diuresis increased with cooling intensity. Additional ADH administration by continuous infusion at a supramaximal dose abolished the diuretic effect of hypothalamic cooling. When water diuresis was induced by intragastric continuous infusion of 1.2 ml . min-1 of distilled water, hypothalamic cooling enhanced the diuresis, but hypothalamic warming had equivocal effects. The diuretic effects of hypothalamic cooling suggest an inhibition of endogeneous ADH release by lowering hypothalamic temperature. When the salt glands of salt adapted ducks were stimulated by continuous intravenous infusion of 0.2 ml . min-1 of 800 mosm . kg-1 NaCl in H2O solution, hypothalamic cooling reduced the salt gland secretion rate to an extent depending on cooling intensity. It is concluded that the activities of those integrative and/or efferent hypothalamic neurons, which mediate the hormonal control of renal water absorption and the nervous control of salt secretion by the supraorbital gland, depend on their own temperature.

Animals↗
PubMed1988

[Drug treatment of heart insufficiency].

Patients with congestive heart failure (CHF) can be treated by diuretics, inotropic agents and vasodilators. Increased diuresis lowers left and right ventricular filling pressures but may further reduce cardiac output. Nevertheless, diuretics produce symptomatic improvement in most patients. Digoxin also has beneficial hemodynamic effects in patients with advanced CHF and sinus rhythm, but the frequency and degree of therapeutic response is inferior to that of vasodilators. Among the latter, ACE inhibitors are the most appropriate for long-term administration since they do not lead to development of tolerance and seem to improve long-term prognosis in patients with severe CHF. Newer inotropic agents have marked hemodynamic effects in the short term, but their utility for chronic treatment remains questionable. The optimum choice of drugs in various forms and stages of CHF is discussed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Efficacy of metolazone and furosemide in children with furosemide-resistant edema.

The effect of a combination of metolazone (0.2 to 0.4 mg/kg/d) and furosemide (2 to 4 mg/kg/d) in achieving a natriuresis and diuresis was measured in 14 children during 22 episodes of edema resistant to furosemide alone. Urinary volume increased from 24 +/- 14 mL/kg/d for patients receiving furosemide to 51 mL/kg/d with combined diuretic therapy (P less than .01), and sodium excretion increased from 34 +/- 5 mEq/d to 155 +/- 176 mEq/d (P less than .01). Two children with severe hypoalbuminemia (serum albumin level less than 1.5 g/dL) and normal renal function, and five children with chronic renal insufficiency (71%) did not respond to combined diuretic therapy. The combination of furosemide and metolazone offers a useful and effective oral therapy in most children with edema resistant to furosemide. Children with chronic renal insufficiency and furosemide-resistant edema did not respond to combination diuretic therapy.

Adolescent↗
PubMed1986

Cirrhotic ascites. Pathophysiology, diagnosis, and management.

Cirrhotic ascites occurs via both overflow and underfill mechanisms. Intrahepatic hypertension activates a hepatic baroreceptor reflex that enhances renal sodium absorption; plasma volume is expanded. As cirrhosis progresses, the hepatoportal Starling forces become sufficiently disturbed to sequester this "overflow" in the peritoneal cavity, which results in ascites formation. "Underfill" of the vascular system occurs and eventually dominates the clinical picture. Finally, intrahepatic hypertension also activates the renin-angiotensin system, which causes renal vasoconstriction; the increase in renal prostaglandin synthesis maintains renal blood flow. Although cirrhotic ascites is traditionally classified as a transudate, the serum-ascites albumin gradient may be a better indicator of ascites secondary to portal hypertension than other causes. General management of patients with cirrhotic ascites includes severe restriction of dietary sodium intake and bed rest; diuretics are added if spontaneous diuresis does not occur after 3 to 4 days.

Animals↗
PubMedDate not supplied

The diuretic action of noradrenaline and dopamine in rats with chemical serotoninectomy and central nervous system sympathectomy.

It was demonstrated that dopamine administered into the lateral ventricle of rats with chemically induced sympathectomy of the central nervous system had an evident diuretic effect observed 4 as well as 24 hours after its injection. Noradrenaline, on the other hand, increased diuresis in control rats and in those with chemical serotoninectomy, but only in the first 4 hours of the experiment. Chemical sympathectomy of the central nervous system abolished the diuretic effect of noradrenaline. The results of the experiment confirm the role of mainly dopaminergic receptors in the central regulation of diuresis in this experimental model.

5,6-Dihydroxytryptamine↗
PubMed1990

Combination of metolazone and furosemide in the treatment of edema in the first month of life.

A combination of metolazone (0.2 mg/kg/day) and furosemide (4 mg/kg/day) was used in the treatment of a 2-week-old neonate who developed severe edema after cardiac surgery. The edema, which was initially responsive to furosemide, became resistant to high doses of this diuretic even with the concomitant use of ethacrynic acid. The addition of metolazone to furosemide induced prompt diuresis and natriuresis. This combination of diuretics can be helpful in the treatment of refractory edema in young infants.

Drug Therapy, Combination↗
PubMed1986

The effect of age and sodium depletion on cardiovascular response to orthostasis.

To test the hypothesis that normal age-related limitations in cardiovascular homeostasis may become clinically significant under stress, the cardiovascular response to postural change was assessed in six young and six old healthy subjects before and after modest diuretic-induced sodium depletion. Before diuresis, systolic blood pressure was maintained (from 110 +/- 4 to 113 +/- 6 mm Hg) while heart rate increased 22% (from 67 +/- 2 to 82 +/- 5 beats/min) at 3 minutes after 60-degree upright tilt in young subjects. After a significant diuretic-induced weight reduction and natriuresis, the young again maintained systolic blood pressure (from 110 +/- 4 to 110 +/- 6 mm Hg) and increased heart rate 49% (from 68 +/- 2 to 101 +/- 5 beats/min; p less than 0.05, compared with prediuresis values) in response to the same postural stimulus. During the prediuresis tilt, the older subjects showed no change in systolic blood pressure (from 132 +/- 4 to 134 +/- 6 mm Hg) and a 9% increase in heart rate (from 68 +/- 3 to 74 +/- 2 beats/min). After a similar significant weight reduction and sodium loss, the older subjects showed a significant reduction in systolic blood pressure (from 132 +/- 6 to 108 +/- 6 mm Hg; p less than 0.05) and a 17% increase in heart rate (from 69 +/- 4 to 81 +/- 3 beats/min; p less than 0.05) during tilt compared with values in young subjects. Three of six elderly subjects noted postural symptoms. These results suggest that, although the healthy old may appear well compensated under optimal conditions, decreased cardiovascular reserve renders them susceptible to postural change following mild sodium depletion.

Adult↗
PubMed1992

Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis.

The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

[Controlled clinical research on the potassium-retaining action of various diuretic drugs].

The potassium-retaining action was evaluated in its kaliemic reflexes, in two diuretic associations composed respectively of hydrochlorothiazide + spironolactone and hydrochlorothiazide + amiloride. The potassium intraerythrocytic levels were also determined as well as the natriuresis, the natremia and the daily diuresis. Researches carried out on a group of patients affected by congestive heart failure showed that, the diuretic efficacy being equal, the association of hydrochlorothiazide + spironolactone does not significantly interfere, at the various posologic levels, with the potassium balance. On the contrary, in this regard, the associaiton of amiloride + hydrochlorothiazide appeared to be less manageable because therapeutic dosages showed a tendency to hyperdaliemia.

Amiloride↗
PubMedDate not supplied

Thoracic duct-subclavian vein anastomosis in management of cirrhotic ascites.

Reanastomosis of the thoracic duct and subclavian vein has been performed in three patients with intractable ascites. Following surgery, these patients were placed on a loop-blocking diuretic plus Aldactone, and prompt diuresis ensued with gradual improvement in the ascites. Improvement in the ascites was probably the result of several factors including removal of obstruction at the upper end of the thoracic duct, mobilization of fluid in the intravascular space, improved lymphatic drainage, and diuretic effect. Complications included necessity for re-exploration in one patient and development of encephalopathy in a second patient.

Adult↗
PubMed2002

Effect of diuresis on P-wave duration and dispersion.

STUDY OBJECTIVE: To evaluate the effects of changing volume status on P-wave duration and dispersion in patients with decompensated heart failure. DESIGN: Prospective analysis. SETTING: Hospital cardiology unit. PATIENTS: Twenty-one patients with symptoms of decompensated heart failure who were treated with diuretics on admission. INTERVENTION: Twelve-lead electrocardiograms were obtained at baseline and after diuresis. Average, minimum, and maximum P-wave duration and P-wave dispersion (minimum minus maximum duration) were determined. MEASUREMENTS AND MAIN RESULTS: P-wave duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. After 40+/-23 hours of diuresis, 3+/-1 L of fluid was removed. A significant correlation was found between average P-wave duration and amount of fluid removed (r = -0.59, p=0.015). Also, average and maximum P-wave duration were significantly decreased with diuresis (p=0.001 and 0.022, respectively). No other P-wave variables were significantly affected. CONCLUSIONS: Diuresis may attenuate electrophysiologic changes caused by fluid overload.

Aged↗
PubMed1981

Investigation of the role of kidney kallikrein on bumetanide induced diuresis in rats.

Administered to anaesthetized, laparatomized rats bumetanide (10 mg/kg intravenously) evoked a rapid and large diuretic response. This was associated with three to five fold enhancements of urine kallikrein (kininogenase) excretion. In addition bumetanide slightly decreased (approximately 10 mmHg) the blood pressure and temporarily increased renal blood flow (less than 10%). The capacity of bumetanide to increase urine kallikrein excretion was inhibited either by pretreatment with chlorazanil (3 mg/kg intravenously) or by the infusion of aprotinin (5000 KIE/kg/min). Kallikrein inhibition did not significantly modify bumetanide induced diuresis, natriuresis, kaliuresis, lowering of blood pressure or renal vasodilating effect.

Animals↗
PubMed1984

Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension.

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.

Antihypertensive Agents↗