Disease relevance of TORSEMIDE

• Vasculitis with acute kidney failure and torasemide [1].
• Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study [2].
• BACKGROUND: The apparent mortality and cardiac benefits seen in studies comparing torasemide with furosemide in CHF suggest that torasemide may have beneficial effects beyond diuresis (e.g., on the process of cardiac fibrosis) [3].
• Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension [4].
• The efficacy of diuretics in acute and chronic renal failure. Focus on torasemide [5].

Psychiatry related information on TORSEMIDE

• Torasemide and water deprivation followed by controlled fluid intake delays but does not reduce the overall mortality due to an LCt70 of PFIB [6].

High impact information on TORSEMIDE

• In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration [2].
• Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08) [2].
• INTRODUCTION: According to in vitro data, torsemide (INN, torasemide) is a substrate of the genetically polymorphic enzyme cytochrome P450 (CYP) 2C9, but the impact of CYP2C9 polymorphisms on torsemide pharmacokinetics and pharmacodynamics has not been studied in humans [7].
• In the present study, the ability of different concentrations of torasemide to modify angiotensin II (Ang II)-induced vascular responses was examined, with the use of an organ bath system, in endothelium-denuded aortic rings from spontaneously hypertensive rats [4].
• Our findings suggest that torasemide blocks the vasoconstrictor action of Ang II in vitro [4].

Chemical compound and disease context of TORSEMIDE

• There are a number of clinically relevant differences between torasemide and the thiazide diuretics in the treatment of hypertension [8].
• In a double-blind randomized multicenter study the antihypertensive efficacy of 2.5 mg torasemide (1- isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfony)urea) and 2.5 mg indapamide was compared in patients with essential hypertension, known as responders to diuretic therapy [9].
• Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous torasemide in rats [10].

Biological context of TORSEMIDE

• Clinical pharmacology of torasemide, a new loop diuretic [11].
• Isometric contraction induced by a submaximal concentration of Ang II (10(-7) mol/L) was reduced in a dose-dependent way by torasemide (IC(50)=0.5+/-0.04 micromol/L) [4].
• In trials of up to 48 weeks' duration in patients with mild to moderate essential hypertension, torasemide, administered as a single daily dose, has been shown to achieve adequate blood pressure control reaching steady-state within 8 to 12 weeks [12].
• Indeed, some common formulations of loop diuretics, such as torasemide 2.5, do not increase 24-hour diuresis or natriuresis in healthy subjects [13].
• In chronic renal failure the renal clearance of torasemide decreased in proportion to the decrease of the patients' glomerular filtration rate, whereas the total plasma clearance (3 times that of the renal clearance) appeared to be independent of renal function [14].

Anatomical context of TORSEMIDE

• Torasemide is similar to other loop diuretics in terms of its mechanism of diuretic action; namely, blockade of Na+/K+/2Cl- cotransport in the thick ascending limb of the loop of Henle [15].
• This conclusion is supported by in vitro observations that torasemide inhibits the swelling of glial cells from acidosis [16].
• In summary, the present investigation provides evidence for a direct contractile effect of the loop diuretic, bumetanide, in contrast to absence of effects by frusemide and torasemide, in ventricular cardiomyocytes isolated from rabbit myocardium [17].
• Torasemide, a loop diuretic, has been reported to relax dog coronary artery precontracted by thromboxane A2 (TXA2), an endogenous prostanoid involved in cardiovascular and pulmonary diseases [18].
• Torasemide is a high-ceiling loop diuretic, useful in correcting extracellular fluid volume expansion in patients with chronic renal failure [19].

Associations of TORSEMIDE with other chemical compounds

• Once daily oral administration of torasemide (starting with 5mg) or furosemide 40mg reduce bodyweight, oedema and symptoms of heart failure to a similar extent [20].
• There was no apparent correlation of genotype to the hydroxylation of the known CYP2C9 substrates phenytoin, tolbutamide, torasemide and diclofenac [21].
• Thus the loop diuretics furosemide and piretanide, the thiazide diuretics hydrochlorothiazide, cyclopenthiazide and bendroflumethiazide and the sulfonylureas tolbutamide, chlorpropamide and torasemide interact with all three tested transport systems for PAH, sulfate and NMeN [22].
• The ability of torasemide to block the vasoconstrictive action of ET-1 could include an inhibitory action on Cl(-) channels [23].
• Addition of glutamate led to a steady increase in cell volume which, contrary to cell swelling from lactacidosis, was not inhibited by torasemide [24].

Gene context of TORSEMIDE

• Bumetanide and torasemide are metabolised by cytochrome P450 pathways, whereas furosemide is glucuronidated [25].
• The present study evaluates the effects of intravenous torasemide on renal function in 25 anesthetized ventilated hypoxemic newborn New Zealand White rabbits with vasomotor nephropathy [26].
• We conclude that in hypoxemic newborn animals with renal dysfunction, torasemide is an effective potassium-sparing diuretic that unfortunately does not improve renal blood flow and GFR [26].
• The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats [23].
• Hence, it could be expected that in rats with PCM, some pharmacokinetic parameters of torasemide could be significantly different compared with those in control rats and rats with PCMC; however, they could be not significantly different between control rats and rats with PCMC [27].

Analytical, diagnostic and therapeutic context of TORSEMIDE

• In clinical trials to date torasemide has been well tolerated with adverse effects of a mild, transient nature reported by only small numbers of patients [12].
• Total plasma clearance of torasemide was reduced to about half of that found in the control group, yielding an increase in elimination half-life [14].
• In the third group of animals (n = 8), torasemide was given preventively; a bolus intravenous dose of torasemide (0.2 mg/kg) was given before the induction of hypoxemia and sustained by the addition of 0.2 mg x kg(-1) x h(-1) of the drug to the continuous intravenous infusion given throughout the entire 3-h hypoxemic period [26].
• Delayed progression of cytotoxic oedema in focal cerebral ischemia after treatment with a torasemide derivative: a diffusion-weighted magnetic resonance imaging study [28].
• Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF [29].

References