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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Torasemide, a new loop diuretic, was administered in 9 hospitalized patients with chronic renal failure to treat both arterial hypertension and peripheral edema. The urine of 5 patients was collected over 12-hour periods to assess the long-lasting diuretic activity of torasemide. Torasemide induced a significant decrease in blood pressure and reversion of peripheral edema in all patients without adverse effects. Torasemide is a high-ceiling loop diuretic, useful in correcting extracellular fluid volume expansion in patients with chronic renal failure.
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PMID:Torasemide, a new loop diuretic, in patients with chronic renal failure. 219 34

The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diuretic, natriuretic and chloruretic effects of torasemide were about 8-times greater than those of furosemide. However, the kaliuretic effect of torasemide was only 3-times greater than that of furosemide, suggesting that torasemide is more potassium sparing than furosemide. Torasemide displayed a rapid onset of action, similar to that of furosemide but had a longer diuretic effect without any rebound phenomenon. Torasemide and furosemide did not effect creatinine clearance or uric acid excretion. Both furosemide and torasemide lowered systolic blood pressure but the effect of torasemide was more marked than that of furosemide. In this group of aged and hypertensive patients with oedema, the pharmacokinetics of torasemide was comparable to that reported in young healthy volunteers, and were similar on the first and fifth days of treatment. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new loop diuretic in the treatment of oedema and hypertension.
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PMID:Torasemide, a new potent diuretic. Double-blind comparison with furosemide. 353 30

Torasemide, a pyridine-3-sulfonylurea derivative, has potent diuretic activity in rats and dogs. In both species urinary volume and electrolyte excretion increased linearly with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. The minimum effective dose by oral route was 0.2 mg/kg in the rat and less that 0.1 mg/kg in the dog. Maximal effect was obtained with about 10 mg/kg. Experiments by oral and i.v. routes in the rat indicated that torasemide was equally potent by both oral and parenteral administration. In both rats and dogs, urinary excretions induced by torasemide were similar to those obtained with furosemide. However, for the same natriuretic effect, potassium losses with torasemide were significantly less than with furosemide. On a weight basis, torasemide was 9-40 times more potent than furosemide in the rat and about 10 times in the dog. After oral administration the diuretic effects of torasemide started within 20 min and lasted approximately 2 h in the rat and more than 8 h in the dog. The activity of torasemide was not decreased after a repeated daily oral dose of 10 mg/kg for 15 days in the rat. Torasemide at a daily oral dose of 5 mg/kg for 12 days effectively reduced the arterial blood pressure in desoxycortone induced hypertension in the rat. Besides the diuretic and antihypertensive effects no other significant pharmacological effects were observed with torasemide in the different in vitro and in vivo experiments. Torasemide was practically fully absorbed by the gastrointestinal tract, its bioavailability by oral route ranged from 80 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological properties of the new potent diuretic torasemide in rats and dogs. 407 7

An important role for diuretics in the treatment of hypertension is assured on the basis of the latest randomized, prospective trials. Although thiazide diuretics have been the mainstay of treatment thus far, they continue to engender debate because of putative, undesirable side effects. Older loop diuretics, such as furosemide, did not establish themselves in the treatment of essential hypertension because of an inferior efficacy profile compared with that of thiazides. Torasemide is a new loop diuretic that is efficacious at low once-daily doses in the treatment of essential hypertension. The drug compares favorably with hydrochlorothiazide and indapamide. Its mechanism of action may not be entirely based on elimination of salt and water from the body. Torasemide exhibits a favorable side-effect profile, particularly because it does not engender hypokalemia, increases in blood sugar, or serum lipid values. When the additional costs of potassium supplements or potassium-retaining medication are considered, torasemide treatment also compares favorably in terms of health-care economics. Torasemide represents a reasonable alternative to conventional diuretic management in patients with essential hypertension.
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PMID:Torasemide in the treatment of arterial hypertension. 750 35

The pharmacological properties and therapeutic use of the high-ceiling loop diuretic torasemide (torsemide) were previously reviewed in Drugs in 1991, the following being a re-examination of the role of the drug in the light of data that have subsequently become available (particularly in the management of oedematous disorders). Torasemide produces a more prolonged water and electrolyte excretion than equipotent diuretic doses of furosemide (frusemide), but does not increase kaliuresis to the same extent. Dosages of torasemide of 2.5 to 5 mg/day do not affect plasma renin activity or aldosterone release to a clinically significant extent, although torasemide 20mg increases plasma renin levels, angiotensin II activity and urinary dopamine and prostaglandin E excretion. Studies published since the previous review have confirmed the efficacy of low dosages of torasemide (2.5 to 5 mg/day) in the treatment of hypertension, and have shown it to be effective when administered orally at a dosage of 5 to 20 mg/day in the management of congestive heart failure. Dosages of up to 400 mg/day increased urinary volume excretion and natriuresis in patients with chronic renal failure. Bodyweight and peripheral oedema were reduced by torasemide 10 to 200 mg/day as monotherapy, and 5 to 20 mg/day when coadministered with spironolactone, in patients with nephrotic syndrome. Dosages of 10 to 40 mg/day, either as monotherapy or in conjunction with an aldosterone antagonist, reduced ascites, oedema and bodyweight in patients with hydropically decompensated liver failure. Adverse effects due to torasemide are usually mild and transient in nature. No evidence of ototoxicity has been demonstrated in humans, and torasemide does not appear to affect blood glucose levels, serum uric acid concentrations, or serum potassium levels at dosages below 5 mg/day. Thus, additional evidence has accumulated for the clinical efficacy of torasemide in the management of mild to moderate essential hypertension and oedematous conditions which require diuretic therapy. Further studies are now required to confirm the long term efficacy and tolerability of torasemide, and to investigate the place of the drug in therapy relative to cardiovascular agents other than furosemide and the thiazide diuretics.
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PMID:Torasemide. An update of its pharmacological properties and therapeutic efficacy. 770 12

In patients with advanced renal failure, high doses of loop diuretics are required to promote negative sodium and water balance and to treat hypertension. Torasemide is a new loop diuretic that has a high bioavailability of 90% and a plasma half-life of 3-5 hours, which remains unchanged in chronic renal failure. Even in patients with advanced renal failure, intravenous and oral high-dose torasemide proves effective in increasing fluid and sodium excretion in a dose-dependent manner. A number of studies in renal failure patients provide evidence that, on a weight-by-weight basis, the ratio of diuretic potency between torasemide and furosemide is 1:2.5 after oral dosing and 1:1 after intravenous administration. The lack of a substantial calciuretic effect of torasemide in chronic renal disease needs further confirmation. Two controlled multicenter clinical trials comparing high oral doses of furosemide and torasemide in patients with end-stage renal disease requiring maintenance hemodialysis demonstrated a substantial increase in urinary volume and electrolyte excretions in patients receiving 100 or 200 mg oral torasemide once daily. A dose of 200 mg oral torasemide appears equally natriuretic to oral furosemide 500 mg, whereas the antihypertensive effect of torasemide is more pronounced. Neither torasemide nor furosemide in the above doses has a negative influence on the neurological status of hemodialysis patients.
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PMID:Torasemide in advanced renal failure. 843 81

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

Torasemide is a lipophilic anilinopyridine sulphonylurea derivative that acts as a high ceiling loop diuretic and has been used for the treatment of both acute and chronic congestive heart failure (CHF) and hypertension. 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. It has high bioavailability (> 80%), as does bumetanide, but a longer elimination half-life (3 to 4 hours) than either bumetanide or furosemide (frusemide). In the treatment of chronic CHF, oral torasemide (5 to 20 mg/day) has been shown to be an effective diuretic. Patients treated with torasemide for up to 1 year have reduced bodyweight, improved pulmonary haemodynamics, and decreased CHF severity. Intravenous torasemide (20 to 60mg as a single dose) has been shown to be as effective as furosemide in the treatment of acute CHF, and resulted in significant diuresis, bodyweight loss, and improved pulmonary haemodynamics and exercise performance. 'Non-diuretic' dosages (2.5 to 5 mg/day) of oral torasemide have been used to treat essential hypertension, both as monotherapy and in combination with other antihypertensive agents. When used in these dosages, torasemide lowered diastolic blood pressure (DBP) to below 90mm Hg in 8 to 12 weeks in 70 to 80% of patients. With dose doubling, this level of efficacy occurred in more than 90% of hypertensive patients. Clinical trials have established that blood pressure can be maintained at this level for at least 1 year with low dose torasemide. Torasemide is well tolerated in dosages up to 20 mg/day for at least 1 year. The most commonly reported adverse effects are those associated with loop diuretics in general. These include transient hypokalaemia, hyperuricaemia, dizziness, headache, gastrointestinal disturbances, orthostatic hypotension and fatigue. Adverse effects are comparable with those of other diuretics and rarely necessitate drug withdrawal.
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PMID:Benefits and risks of torasemide in congestive heart failure and essential hypertension. 885 25

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

Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension. Because its antihypertensive mechanism of action may not be based entirely on the elimination of salt and water from the body, a vasodilator effect of this drug can be considered. 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. Ang II-induced increases of intracellular free calcium concentration ([Ca(2+)](i)) were also examined by image analysis in cultured vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A dose-response curve to Ang II was plotted for cumulative concentrations (from 10(-9) to 10(-6) mol/L) in endothelium-denuded aortic rings (pD(2)=7.5+/-0.3). 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). Incubation of VSMCs with different concentrations of Ang II (from 10(-10) to 10(-6) mol/L) resulted in a dose-dependent rise of [Ca(2+)](i) (pD(2)=7.5+/-0.3). The stimulatory effect of [Ca(2+)](i) induced by a submaximal concentration of Ang II (10(-7) mol/L) was blocked by torasemide (IC(50)=0.5+/-0.3 nmol/L). Our findings suggest that torasemide blocks the vasoconstrictor action of Ang II in vitro. This action can be related to the ability of torasemide to block the increase of [Ca(2+)](i) induced by Ang II in VSMCs. It is proposed that these actions might be involved in the antihypertensive effect of torasemide observed in vivo.
Hypertension 1999 Jul
PMID:Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. 1040 37


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