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D E Hutcheon

Publications and source records attributed to D E Hutcheon.

23 records · Page 2Linked to original sources
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Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion.

The purpose of this study was to compare the renal electrolyte excretion pattern of bumetanide with that of hydrochlorothiazide in dogs anesthetized with pentobarbital. In bumetanide-treated animals, mean sodium excretion rose to 12 per cent of the filtered load, while hydrochlorothiazide increased sodium excretion to 4 per cent of the filtered load. After bumetanide, urine pH fell from 6.1 to 5.1 and net hydrogenion excretion increased significantly. After hydrochlorothiazide, urinary pH went from 6.4 to 7.4, and there was no change in net hydrogen ion excretion. Potassium excretion rose to 106+/-22 muEq/min with bumetanide and to 99+/-17 muEq/min with hydrochlorothiazide. These changes in electrolyte excretion occurred despite lack of changes in arterial blood gases, arterial blood pressure, and glomerular filtration rate. In addition, bumetanide did not exert an inhibitory effect on potassium excretion under conditions of potassium loading. It is concluded that bumetanide produces a higher urinary Na+:K+ ratio with a lower pH than hydrochlorothiazide and that renal potassium ion excretion in response to sulfamoyl diuretics is not solely dependent on the rate of sodium excretion.

Animals↗
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Renal electrolyte excretion pattern in response to bumetanide in healthy volunteers.

Renal electrolyte excretion patterns were determined in nonedematous healthy volunteers following bumetanide and furosemide in two separate clinical studies. In study 1, intravenous bumetanide was administered to 24 subjects at four dose levels. In study 2, bumetanide (1 or 2 mg) or furosemide (40 or 80 mg) was administered in a single oral dose to 32 subjects assigned at random to one of the four treatment groups. In study 1, there was a significant dose-related increase in urine volume and sodium, potassium, and chloride excretion, with chloride exceeding sodium at all dose levels, and the Na+/K+ ratios after bumetanide were greater than 3:1. In study 2, the Na+/K+ ratio increased significantly after treatment in all four treatment groups. The relative Na+/K+ ratios showed higher natriuretic potency and lower kaliuretic potency for bumetanide than for furosemide, but the differences were not statistically significant. Additionally, all four treatment groups demonstrated elevation in titratable acidity, ammonia formation, and total acid excretion. There was a significant degree of positive correlation in the bumetanide-treated groups between Na+/K+ and the three variables. In the furosemide-treated groups, this positive correlation was statistically significant between the Na+/K+ ratio and ammonia and total acid secretion but not for titratable acidity. The results support the view that increased H+ formation after the administration of loop diuretics has a relative potassium-sparing effect.

Adult↗
PubMedDate not supplied

A decade of developments in diuretic drug therapy.

New diuretics introduced into clinical medicine during the past decade include potent new loop diuretics such as bumetanide and piretanide, the uricosuric indanyloxyacetic acid derivative indacrinone, and a new generation of sulfamoyl diuretics such as indapamide and xipamide, which are recommended primarily for the treatment of hypertension. Pharmacokinetic studies of individual diuretics have demonstrated that the diuretic and natriuretic responses to the newer agents generally follow the plasma drug concentration-time curves and urinary drug excretion rates. Therapeutic monitoring can therefore be achieved in most patients with edema or hypertension by close clinical observation and laboratory analysis of plasma electrolyte and creatinine concentrations and urinary electrolyte excretion rates. Interest in the mechanisms involved in the renal and extrarenal vascular actions of the newer diuretics has led to a better understanding of how changes in venous compliance, peripheral vascular resistance, and renal blood flow distribution may contribute to the overall therapeutic response to these agents, especially in patients with severe congestive heart failure, renal insufficiency with low glomerular filtration rates, and hypertension with cardiorenal complications. Adverse reactions to modern diuretics, which are mainly an extension of their renal pharmacodynamic effects, have proved to be minimal, provided that the dosage is adjusted to meet but not exceed individual patient requirements. However, the long-term consequences of prolonged periods of diuretic-induced alterations in plasma potassium levels, and metabolic effects that include elevated blood lipids, are still under investigation.

Diuretics↗