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At least 577 records · Page 32Linked to original sources
PubMed1983

Determinants of bumetanide response in the dog: effect of indomethacin.

Four male unanesthetized dogs each weighing 22.0-29.0 kg received 0.250 mg/kg iv of bumetanide before (treatment I) and after (treatment II) indomethacin pretreatment. Lactated Ringer's solution was administered intravenously throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Unchanged bumetanide and indomethacin concentrations were analyzed using high-performance liquid chromatography. Sodium was measured by flame photometry and creatinine by colorimetry. Indomethacin pretreatment did not significantly change the pharmacokinetics of bumetanide, affecting neither the total amount of drug nor time course of drug delivered into the urine. In contrast, indomethacin pretreatment resulted in a dramatic reduction in the 4-hr sodium excretion and urine volume. Therefore, a pharmacokinetic interaction may be eliminated as a possible mechanism for the attenuation, by indomethacin, of the natriuretic and diuretic response of bumetanide. Instead, it appears that indomethacin diminishes the response to bumetanide via prostaglandin inhibition.

Animals↗
PubMed1988

An examination of the site and mechanism of action of torasemide in man.

Acute clearance studies were performed in normal subjects to determine the site and mechanism of action of torasemide (isopropyl-1-methyl-3 phenylamino-4 pyridil-3 sulphonyl-3-urea), a new diuretic agent, in the human kidney. The drug caused no change in glomerular filtration rate or effective renal plasma flow. Sodium excretion rose to 16% of filtered load, whereas there was a chloriuresis of 23%. During maximal water diuresis, the drug caused an increase in urine flow rate and a decrease in solute-free water clearance. Administration of the drug during hypertonic saline infusion into hydropenic subjects resulted in a marked decrease in water reabsorption from the collecting duct. Torasemide caused no change in phosphate excretion or in the percentage of filtered bicarbonate excreted, nor was urinary pH or net hydrogen ion excretion affected by the drug. The data suggest that the primary site of action of torasemide is the medullary portion of the ascending limb of the loop of Henle.

Acid-Base Equilibrium↗
PubMed1993

Renal excretory profiles of loop diuretics: consequences for therapeutic application.

In healthy subjects, 24-h natriuresis, kaliuresis, calciuresis, and magnesiuresis increase in response to the first oral dose of a standard (diuretic) formulation of a loop diuretic, such as furosemide 40 mg. However, low-dose formulations of loop diuretics, such as torasemide 2.5 mg, do not elevate 24-h natriuresis after the first dose is administered to normal individuals who are in steady-state habitual sodium balance; these formulations of loop diuretics are consequently labeled as nondiuretic formulations (of diuretic substances). Nondiuretic formulations of loop diuretics do not increase the 24-h urinary outputs of sodium, potassium, calcium, or magnesium after the first dose or in the course of repeated once-daily administration to healthy subjects. The 24-h natriuretic response to the first dose of standard (diuretic) formulations of loop diuretics wanes during repeated once-daily administration to healthy individuals, whereas the kaliuretic response becomes slightly attenuated, and calciuresis and magnesiuresis bear little change. Once-daily treatment with any formulation of a loop diuretic may result in an increase in plasma urate concentration. Nondiuretic formulations of loop diuretics, which are efficacious as once-daily monopharmacotherapy for high blood pressure, should be tried before standard (diuretic) formulations of diuretics are used in the treatment of uncomplicated essential hypertension. When loop diuretics are employed in the treatment of congestive heart failure, the minimal dose compatible with the attainment of clinical objectives should be used.

Diuresis↗
PubMed1978

Comparative natriuretic and diuretic efficacy of theophylline ethylenediamine and of bendroflumethiazide during long-term treatment with the potent diuretic bumetanide. Permutation trial tests in patients with congestive heart failure.

The additive natriuretic and diuretic effects of theophylline ethylenediamine and of bendroflumethiazide have been compared in permutation trial tests in patients with advanced congestive heart failure receiving long-term treatment with the highly potent diuretic, bumetanide. Statistical analysis of renal water and electrolyte excretion revealed that theophylline ethylenediamine, 400 mg orally, and bendroflumethiazide, 5 mg orally, had very similar effects, both quantitatively and qualitatively. The mechanism of action of the supplementary diuretics is discussed. It is concluded that theophylline ethylenediamine represents a useful alternative to thiazide diuretics when supplementary natriuretic treatment is considered in patients with congestive heart failure during long-term treatment with potent diuretics. The significance of maintaining the potassium balance during such a combined regimen is stressed.

Bendroflumethiazide↗
PubMed1989

Diuretic effect induced by intrarenal infusion of nisoldipine in anaesthetized dogs.

1. Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of nisoldipine (10, 50 ng/kg per min) did not influence mean systemic blood pressure and renal haemodynamics, but did cause dose-related increases in urine flow and urinary excretion of electrolytes. During nisoldipine infusion at the higher dose, the levels of fractional excretion of sodium, potassium and chloride were significantly elevated. 3. In the lithium clearance study, fractional lithium excretion, an index of fractional sodium excretion in the proximal tubules, was unchanged even with the higher dose of nisoldipine, whereas fractional sodium excretion in the distal tubules markedly increased. 4. Nisoldipine elicited a significant increment in osmolar clearance without altering the reabsorption of free water. 5. Thus, intrarenal administration of nisoldipine at a non-hypotensive dose to anaesthetized dogs produced a significant diuretic effect without alteration in renal haemodynamics. Results in lithium clearance and free water clearance studies suggest that nisoldipine exerts a diuretic action by inhibiting sodium transport at the distal nephron segments beyond the proximal tubules.

Anesthesia↗