Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

Abstract

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 HCTinduced 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.

Should Torsemide Be the Loop Diuretic of Choice in Systolic Heart failure?

“…Moreover, torsemide has been shown to cause less hypokalemia compared with furosemide [34]. Thus, the addition of torsemide to hydrochlorothiazide significantly reduces potassium and magnesium loss and at the same time improves natriuresis; an effect that would not be observed with furosemide [33,34]. It is also common for clinicians to add a potassium-sparing diuretic, such as amiloride or triamterene, to a thiazide diuretic to prevent hypokalemia.…”

“…Moreover, torsemide may also prevent loop diuretic resistance, whereas these benefits would not be expected to be seen with furosemide. Furthermore, torsemide may be a better option to prevent thiazide-induced hypokalemia compared with a potassium-sparing diuretic such as triamterene or amiloride [33,35]. However, there needs to be more data before this can be confirmed.…”

“…However, the addition of [36] Murray et al (2001) [48] Total (95% CI) Total events Heterogeneity: tau 2 = 0.00; χ 2 = 0.23, df = 1 (p = 0.63); I 2 = 0% Test for overall effect: Z = 4.39 (p < 0.0001) [36] Murray et al (2001) [48] Total (95% CI) Total events Heterogeneity: tau 2 = 0.00; χ 2 = 0.04, df = 1 (p = 0.84); I 2 = 0% Test for overall effect: Z = 2.67 (p = 0.008) future science group a thiazide diuretic increases the chance of electrolyte disturbances such as hypokalemia and hypomagnesemia. Despite this fact, the addition of torsemide to hydrochlorothiazide significantly reduced potassium and magnesium loss caused by hydrochlorothiazide, while at the same time increasing natriuresis [33]. This added benefit of torsemide is presumed to be due to its antialdosterone effects, which would not be seen with furosemide [34].…”

Combination of Loop Diuretics With Thiazide-Type Diuretics in Heart Failure

“…Metolazone has slow and variable absorption in edematous patients, such that the peak effect occurs only after several hours (15,45). The benefit of TD (with their long duration of action) added to LD appears to be primarily in maintaining diuresis after the shorter-acting LD has worn off (49,53).…”

“…Increases in serum creatinine on the order of 20% to 30% were frequently reported. TD alone initially produce a reversible reduction in glomerular filtration rate during peak natriuresis (47), which may be attenuated by the addition of LD (53). Chronic TD use is 1 predictor of worsening renal function in chronic heart failure patients (60), and the potential for worsening renal function is an important concern with CDT, given the adverse prognosis associated with worsening renal function in patients with heart failure (61).…”