Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Torasemide (torsemide) is a high-ceiling loop diuretic which acts on the thick ascending limb of the loop of Henle to promote rapid and marked excretion of water, sodium and chloride. Like furosemide (frusemide), its major site of action is from the luminal side of the cell. Torasemide is at least twice as potent as furosemide on a weight-for-weight basis, produces equivalent diuresis and natriuresis at lower urinary concentrations and has a longer duration of action, allowing once-daily administration without the paradoxical antidiuresis seen with furosemide. Torasemide also appears to promote excretion of potassium and calcium to a lesser extent than furosemide. 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. Those patients not responding initially have generally responded to a doubling of the dose. Comparative trials of up to 6 months show torasemide is as effective as indapamide, hydrochlorothiazide or a combination of triamterene/hydrochlorothiazide in maintaining control of blood pressure. Torasemide has also been used successfully to treat oedematous states associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. In short term trials control of blood pressure, bodyweight and residual oedema has been sustained. Torasemide appears to be a useful alternative to furosemide in these patients, providing potent and long-lasting diuresis while being relatively potassium and calcium sparing. 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. Changes in biochemical parameters have been common, including decreases in plasma sodium and potassium levels and increases in plasma creatinine and uric acid levels. These changes are typical of loop diuretics. No changes were clinically significant nor were clinically relevant changes noted in glucose metabolism, cholesterol or triglyceride levels or in haematological values. Thus, torasemide is an interesting new loop diuretic with potential use in the treatment of mild to moderate essential hypertension and of oedematous states in which diuretic therapy is warranted. Preliminary studies suggest it to be as efficacious as other diuretics in common use and to have some advantage over furosemide in duration of action and in effects on potassium and calcium. However, further long term trials in larger groups of patients are needed to delineate the place of torasemide in therapy fully, both as a single agent and in combination with other currently accepted drug regimens.
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PMID:Torasemide. A review of its pharmacological properties and therapeutic potential. 170 90

The pharmacodynamics of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new potent loop diuretic, were compared to those of furosemide in a double-blind controlled study in 18 patients with oedema of various origin. Torasemide behaved like furosemide in exerting a potent diuretic effect which culminated during the first 4 h after its administration. Nevertheless, torasemide was about 8 times more potent, exerted a longer lasting diuretic effect and was more potassium sparing than furosemide. Torasemide did not accumulate during repeated administration (5 days). It was well tolerated and efficient in the treatment of oedema due to congestive heart failure and hepatic cirrhosis. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new potent loop diuretic.
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PMID:Comparative pharmacodynamics of torasemide and furosemide in patients with oedema. 328 31

Torasemide is a new loop diuretic that differs from others in this class in that only 20% of the drug is excreted unchanged in the urine with the remaining 80% being eliminated by hepatic metabolism. The large component of nonrenal clearance would predict that torasemide would have only minimal accumulation and prolongation of half-life in patients with renal insufficiency, and this proves to be the case. In contrast, in patients with liver disease, impairment of hepatic elimination causes accumulation of torasemide in plasma with prolongation of half-life. In addition, in cirrhosis, there is increased elimination of unchanged drug into the urine compared to healthy controls. In patients with renal insufficiency, response to remaining nephrons is normal as has been observed with other loop diuretics. In patients with cirrhosis and in those with congestive heart failure, response is diminished, again as has been observed with other loop diuretics. Interestingly, in patients with cirrhosis, the increased delivery of drug into the urine is sufficient to compensate for the decreased pharmacodynamics of response so that overall response is similar to that which occurs in health subjects.
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PMID:Pharmacokinetics and pharmacodynamics of torasemide in health and disease. 750 34

This review concerns studies of the comparative efficacy and safety of torasemide and furosemide in patients with cirrhosis of the liver complicated by ascites and oedema. The short-term trials reviewed indicated that in patients who had failed to respond with adequate diuresis and loss of body weight and ascites to bed rest, restricted salt and water intake and spironolactone, torasemide had a longer duration of action than furosemide and resulted in a greater urinary excretion of salt and water and greater loss of body weight. Torasemide also had less effect than furosemide on urinary potassium excretion and unlike furosemide did not increase the fractional excretion of magnesium or phosphate or the blood ammonia concentration. Two longer term trials in similar patients with decompensated hepatic cirrhosis confirm the results of the shorter term studies. These studies, albeit each in relatively small numbers of patients, confirm the ability of torasemide to enhance diuresis, free water clearance and fractional excretion of sodium and chloride, resulting in loss of body weight and mobilization of ascites in patients with decompensated hepatic cirrhosis. In these patients, the relatively small increase in urinary excretion of potassium, induced by torasemide without any marked effect on renal function or on the plasma neurohormonal profile, enhances its potential safety.
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PMID:Comparative analysis of torasemide and furosemide in liver cirrhosis. 795 49

Torasemide is a new loop diuretic with a longer half-life and longer action than furosemide in healthy subjects. In order to evaluate the pharmacodynamic effects, single oral doses of furosemide (80 mg) and torasemide (20 mg), which were equipotent in healthy subjects, were given to 14 patients with cirrhosis and ascites. Before the study patients underwent an equilibration period of 4 days without diuretics. The drugs were alternated following a randomized double-blind cross-over design after a wash-out period of at least 2 days. Urine was collected at defined intervals for 24 h after drug administration and blood samples were taken before, 6 h and 24 h after medication. Torasemide induced greater cumulative 24 h diuresis (2863 +/- 343 vs. 2111 +/- 184 ml, p < 0.01) than furosemide. Torasemide did not differ from furosemide for cumulative 0-6 h sodium excretion (96 +/- 17 vs. 92 +/- 23 mmol sodium) but caused a more pronounced cumulative 6-24 h natriuresis (38 +/- 11 vs. 17 +/- 4 mmol, p < 0.05). Five patients exhibited a weak response to furosemide (0-36 mmol sodium/24 h, median 24 mmol; 690-1460 ml urinary volume/24 h, median 1325 ml). These patients showed significantly higher natriuresis and diuresis following torasemide (26-136 mmol sodium/24 h, median 78 mmol, p < 0.05; 1670-3610 ml urinary volume/24 h, median 2200 ml, p < 0.05). Twenty-four hours after administration of both drugs there were no significant changes in hemodynamic, renal or hormonal parameters. No adverse effects were noted with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Advantages of the new loop diuretic torasemide over furosemide in patients with cirrhosis and ascites. A randomized, double blind cross-over trial. 831 63

The bioavailability, pharmacokinetics, and pharmacodynamics of torsemide (10 mg orally and intravenously) were determined in a randomized crossover clinical trial with 12 patients with ascites caused by cirrhosis. Torsemide was rapidly absorbed with a bioavailability of 96.3% (confidence interval, 84% to 109%). Compared with healthy subjects, patients with cirrhosis exhibit a decrease in nonrenal clearance and increases in bioavailability, volume of distribution, renal clearance, elimination half-life, and percentage of the dose excreted into the urine. A greater proportion of the dose is delivered to the site of action over a more prolonged period of time. In spite of a shift of the pharmacodynamic curve to the right in patients with cirrhosis, there was no significant difference in natriuresis. Pharmacokinetic changes of torsemide in cirrhosis therefore compensate for the pharmacodynamic abnormality.
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PMID:Bioavailability, pharmacokinetics, and pharmacodynamics of torsemide in patients with cirrhosis. 833 Apr 70

The effects of torasemide (20 mg/day) and furosemide (50 mg/day), each given over 4 days, were compared in a randomized and crossover study carried out in seven patients with cirrhosis and tense ascites. Patients also received a low-sodium (40 mmol/day) diet and the aldosterone antagonist, potassium canrenoate (100 mg b.i.d.). Torasemide induced a remarkably higher natriuretic (120 +/- 15 vs. 33 +/- 6 mmol/day, p < 0.02) and diuretic (1450 +/- 63 vs. 900 +/- 58 ml, p < 0.005) effect than furosemide. Body weight loss was also significantly higher (2.5 +/- 1.6 vs. 0.2 +/- 1.3 kg, p < 0.01) during the torasemide period. Kaliuresis was similar during the two treatment periods, despite the striking differences observed in natriuresis. Neither torasemide nor furosemide induced any significant change in serum electrolyte or creatinine concentrations, or in ammonia levels. The results of this study indicate that torasemide is suitable for the treatment of sodium retention in patients with cirrhosis and ascites.
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PMID:Torasemide in the treatment of patients with cirrhosis and ascites. 843 82

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of torsemide are reviewed. Torsemide belongs to the pyridine-sulfonylurea class of loop diuretics. Its primary site of activity is the thick ascending limb of the loop of Henle, where it blocks active reabsorption of sodium and chloride, resulting in diuresis, natriuresis, and other effects. Torsemide has high bioavailability, a relatively long half-life, and a prolonged duration of activity. It is highly protein bound. Clinical trials indicate that torsemide is effective in the treatment of hypertension and of edema and other symptoms in patients with chronic renal failure (CRF), hepatic dysfunction, or congestive heart failure (CHF). Torsemide has infrequent, mild, and transient adverse effects; among the most common are orthostatic hypotension, fatigue, dizziness, and nervousness. The recommended initial oral dosages of torsemide are 10-20 mg/day for CHF, 20 mg/day for CRF, 5 mg/day for hypertension, and 5-10 mg/day (in combination with a potassium-sparing diuretic or aldosterone antagonist) for hepatic cirrhosis. In most patients, the pharmacokinetic advantages of torsemide over other loop diuretics are unlikely to translate into a substantial edge in clinical outcomes, and in practice there may be no cost advantages. Although torsemide does not offer major advantages over other loop diuretics, it may be of benefit in patients who do not respond to or cannot tolerate other agents.
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PMID:Torsemide: a new loop diuretic. 852 33

The new loop diuretic torasemide belongs to the pyridine sulfonylurea class. It is well absorbed and yields a bioavailablity of about 80% in healthy individuals, even higher in patients with oedema. This is roughly double that of the 'classical' loop diuretic furosemide (frusemide) [26 to 65%]. Torasemide is highly bound to protein (99%) as is furosemide. The volume of distribution of torasemide was determined as 0.2 L/kg as compared with 0.11 to 0.18 L/kg for furosemide. Torasemide undergoes extensive hepatic metabolism; only 20% of the parent drug is recovered unchanged in the urine. For comparison only 10 to 20% of furosemide undergoes phase II metabolisation (to the glucuronide). 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. As expected, the renal excretion of torasemide metabolites is significantly retarded in renal disease. The pharmacokinetics of torasemide are significantly influenced by liver disease. Total plasma clearance of torasemide was reduced to about half of that found in the control group, yielding an increase in elimination half-life. A greater than normal fraction of torasemide was recovered in the urine of patients with cirrhosis. In contrast, the kinetics of furosemide appeared to depend more on kidney function than on liver disease. The pharmacodynamics of torasemide are principally the same as those reported from conventional loop diuretics due to their interference with one binding site in the thick ascending limb of Henle's loop, the Na+:K+:2Cl- carrier. The maximum natriuretic effect of all loop diuretics amounts to about 3 mmol Na+/min. Members of this class differ, however, with respect to their intravenous potency or affinity for the receptor, respectively: bumetanide > piretanide > torasemide > furosemide. So far, the only loop diuretic which has been shown to effectively lower high blood pressure is torasemide. This effect occurs at the low dose of 2.5 mg/day.
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PMID:Clinical pharmacokinetics and pharmacodynamics of torasemide. 947 71