Knauf H, Mutschler E, Velazquez H, Giebisch G
Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis. [JOURNAL ARTICLE]
Eur J Clin Pharmacol 2009 Feb 20.
BACKGROUND: Resistance to high-dose loop diuretics can be overcome either by co-administration with thiazides or by treatment with medium-dose loop diuretics combined with thiazides. Combination therapy has been proven to be superior to high-dose loop diuretic monotherapy for cardiac and renal edema. However, such a strongly efficacious short-term regimen is often complicated by undesired effects, including circulatory collapse and electrolyte disturbances. The question of whether the loop diuretic/thiazide combinations are efficacious and safe when conventional doses are combined has not yet been answered.
METHODS: The effects of hydrochlorothiazide (HCT) and torasemide (TO) given alone on the excretion of Na(+), Cl(-), K(+), Mg(2+), and Ca(2+) were compared with the effects of combined administration of the diuretics in 12 healthy volunteers.
RESULTS: The co-administration of HCT (25 mg) with TO (5 or 10 mg) strongly increased Na(+) excretion. However, the combination significantly reduced K(+) and Mg(2+) excretion. The K(+)-sparing effect of the HCT/TO combination was shown to be due to a significant reduction in the HCT-induced increase in fractional K(+) excretion by the loop diuretic. Total excretion of Ca(2+) relative to Na(+) excretion was less with the HCT/TO combination than with TO given alone.
CONCLUSION: The enhancement of desired NaCl excretion by the HCT/TO combination with significant reduction of undesired loss of K(+) and Mg(2+) meets clinical requirements but has to be validated in long-term clinical trials.
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