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Summary
Loop diuretics in high doses are the drugs of choice in the treatment of both acute
renal failure (ARF) and chronic renal failure (CRF). Their pharmacokinetic and pharmacodynamic properties give them a high efficacy, even in severely compromised renal
function. The serum elimination half-life and duration of action of most loop diuretics
are dependent on the glomerular filtration rate and are therefore prolonged in renal failure. Torasemide, a new high ceiling and long acting loop diuretic, is as potent as furosemide (frusemide) in patients with advanced renal failure. Unlike other loop diuretics
the half-life and duration of action of torasemide are not dependent on renal function
and the parent drug does not accumulate in renal failure. The extent of metabolism is
clinically negligible. A number of studies have demonstrated the efficacy of furosemide
bumetanide, piretanide and torasemide in patients with ARF and CRF. When compared
with the other loop diuretics, torasemide has the following advantages: a longer half-life
independent of renal function, no indications of toxic side effects and apparently less
influence on calciuresis.
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Fig. 1. Correlation of the amount of drug excreted into the urine (dotted lines) and sodium excretion (bars) for (a) torasemide
and (b) furosemide (frusemide) after single intravenous administration. Time 0 denotes administration of the drugs.Urine
was collected during 0 to 6, 6 to 12, 12 to 24 hours on a preceding control day, the day after administration of the drug,
and on the second day thereafter. * = significant differences from the respective collection period of the preceding contra
day (adapted from Klutsch et al. 1988: Kult et al. 1990, with permission).
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prostagiandins, (catecholarnines,) renin and aldosterone in patients with ARF. It was shown that
loop diuretics in high doses increased
vasodilatory
Table II. Effect of torasemide 20mg and 100mg, furosemide (frusemide) 60mg and placebo after single intravenous (IV) doses on 24hour volume, sodium, potassium, chloride and calcium excretion in patients with chronic renal failure. Data are presented as a
mean percentage increase over the preceding control day (adapted from Mourad et al. 1988)
Change from control value (%)
no. of patients
volume
sodium
potassium
chloride
calcium
Torasemide 20mg IV
11
NS
+34
NS
+52
NS
Torasemide 100mg IV
10
+26
+78
NS
+127
NS
Furosemide 60mg IV
13
+32
+55
NS
+72
+40
Placebo
12
NS
NS
NS
NS
NS
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3.2.1 Haemodialysis
Loop diuretics have also been used to treat
patients on haemodialysis. Patients with a residual
diuresis of 200 to 500ml benefit from diuretic
therapy; their urinary output increases, and their
fluid intake may be increased accordingly. The advantages of this treatment are gains in patient comfort and quality of life. Schulz et al. (1990) have
compared the effect of torasemide 200mg with furosemide 500mg and placebo in 80 patients over a
3-month treatment period.
This randomised
double-blihd trial demonstrated an increased urinary output of water, sodium and chloride in both
actively treated groups compared with placebo.
After 3 months, neurological examination dem-
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Fig. 3. Reduction in blood pressure (bars) and bodyweight (line) in hypertensive patients with chronic renal failure during
9 days' treatment with intravenous torasemide (0.77 mg/kg bodyweight; from Russo et al. 1990, with permission).
* .= p < 0.0025; ** = p < 0.0005.
4. Conclusion
Torasemide is a high ceiling diuretic which, in
comparison with furosemide, has a longer elimination half-life independent of renal function. Torasemide increased fractional excretion of volume
and sodium dose-dependently up to 200mg orally
or intravenously in patients with CRF. Calcium
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et. al. (Eds) Torasemide: Clinical Pharmacology and Therapeutic Applications. Progress in Pharmacology and Clinical
pharmacology vol. 84 no.81,93. Gustav Fisher Verlag, Stutigart.
1990
Kramer BK. Risier T Xipamide- Cardiovascular Drug Review, 6:
141-154, 1988
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patients with advanced chronic renal failure. Arzneimittel-Forschung 38: 212-214. 1988
Kult J, Ziegler J, von Mollendorf E. Pharmacodynamics and
pharmacokinetics of torasemide and furosemide in patients with
high grade renal failure after application of high intravenous
doses. In Kruck et al. (Eds) Torasemide: Clinical Pharmacology and Therapeutic Applications. Progress in Pharmacology
and Clinical Pharmacology Vol. 8/1, pp. 239-248, Gustav
Fischer Verlag, Stuttgart, 1990
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subjects and patients with chronic renal failure. Clinical
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Lesne M. Comparison of the pharmacokinetics and pharmacodynamics of torasemide and furosemide in healthy volunteers.
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Levine SD. Diuretics. Medical Clinics of North America 73: 271282, 1989
Loute G, Adam A, Ers P, Heremans C, Willems B. The influence
of haemodialysis and haemofiltration on the clearance of torasemide in renal failure. European Journal of Clinical
Pharmacology 31 (Suppl.): 53-55, 1986
Mackay IG, Muir AL, Watson ML. Contribution of prostaglandins to the systemic and renal vascular response to furosemide
in normal man. British Journal of Clinical Pharmacology 17:
513-519, 1984
Maharaj B. Diuretics in retinal failure. Progress in Pharmacology
6: 267-288, 1988
Marcantonio LA, Auld WKR, Murdoch WR, Purohit R, Skellern
GG, et al. The pharmacokinetics and pharmacodynamics of
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Correspondence and reprints: Dr Teut Risler, Section of Nephrology and Hypertension, Department of Medicine III, University
of Tubingen, Otfried-Muller-Strasse 10, 74 Tubingen, Federal Republic of Germany.