Comparative Pharmacokinetics and Pharmacodynamics of Loop Diuretics in Renal Failure

Abstract

Loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride and calcium in all stages of renal failure, and their potency is directly correlated with these excretory activities. Tubular secretion of loop diuretics in renal failure is impaired both by reduced renal blood flow and by reduced activity of the tubular carrier system. For these reasons, high concentrations of diuretics in the peritubular capillaries are necessary to guarantee delivery of sufficient drug to their site of action in the ascending limb of the loop of Henle. Piretanide and furosemide have a constant extrarenal elimination and thus accumulate in renal failure. Decreased renal excretion of bumetanide is compensated by hepatic elimination and hence bumetanide does not accumulate. Elimination of torasemide is also independent of its renal excretion. Thus in renal failure, torasemide is the only loop diuretic in which the plasma concentration is strictly dose dependent. Loop diuretics follow a number of different metabolic pathways, but this may not be clinically relevant.

Torsemide Versus Furosemide After Continuous Renal Replacement Therapy Due to Acute Renal Failure in Cardiac Surgery Patients

“…[6,7] In CRF and ARF, both diuretics, in a bolus dosage of 100 -250 mg intravenously, have shown to significantly increase urine output. [8,9,15,16,20] This effect was more pronounced for torsemide in some studies. [8] Shilliday et al [17] compared the use of furosemide, torsemide, and placebo in a bolus intravenous application of 3 mg/kg every 6 h in ARF patients who were, however, at the same time treated with mannitol and dopamine infusion.…”

“…[8,9,15,16,20] This effect was more pronounced for torsemide in some studies. [8] Shilliday et al [17] compared the use of furosemide, torsemide, and placebo in a bolus intravenous application of 3 mg/kg every 6 h in ARF patients who were, however, at the same time treated with mannitol and dopamine infusion. Urine output was significantly higher in the diuretics group, whereas the need for dialysis and outcome were not different between the groups.…”

“…[6] The dosage for torsemide was adjusted according to the previously described pharmacological characteristics of torsemide. [6,8] The double potency of torsemide is reflected in this study, because furosemide was dosed twice as high as torsemide in almost every time interval. In ARF, continuous infusion versus high boluses of loop diuretics have been shown to be potentially superior regarding effectiveness and toxicity.…”

“…Torsemide was given in equipotent doses to furosemide, and we expected similar natriuresis in both groups, as described in some studies. [8,10,11,15] Other studies, however, describe an increased dose-dependent saluretic effect of torsemide. [8,15] This might have happened in our study.…”

“…[6,7] Torsemide is mainly metabolized in the liver (80%) and, in contrast to furosemide, which is mainly metabolized and excreted in the kidneys, does not accumulate in renal failure. [6,8] Torsemide causes a greater sodium and chloride excretion than furosemide, whereas urinary potassium excretion rises to a much lesser extent under torsemide application. [6,9] Reduced kaliuresis has been described in in vitro, animal, and human studies in chronic heart failure (CHF) and chronic renal failure (CRF) patients and was attributed to the inhibition of aldosterone binding to the receptor, causing an anti-aldosteronic effect.…”