Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Torasemide 40 mg/day p.o. was administered for 21 days to 8 healthy volunteers to investigate its pharmacodynamics, pharmacokinetics and safety on chronic administration. It induced a highly significant initial increase in 24-h urinary volume and 24-h excretion of sodium and chloride, but its affect diminished after the first days. On Days 0, 1, 10 and 21 the experiment was divided in 3 clearance phases, extending from 0 to 2 h, 2 to 6 h and 6 to 24 h after dosing. The fractional excretion of sodium, chloride, potassium, calcium, magnesium and inorganic phosphates peaked during the first 2 h and returned almost to the control value during the following two clearance phases. The phase-dependent changes were significant for all electrolytes, except for potassium and inorganic phosphate. Plasma electrolyte levels remained constant throughout the study, except for a small decrease in chloride and potassium and for an increase in calcium and magnesium. Fasting blood glucose and glucose tolerance test were unaffected. A small but significant decrease in LDL-cholesterol was observed on Day 10. Other plasma lipid components showed minor changes. Plasma uric acid levels were moderately increased. There was no significant change of the creatinine clearance. Body weight fell significantly (by about 2 kg) during the study. Tonal audiometry was normal before and after the study. There was no significant difference between the plasma levels of torasemide on Days 1, 10 and 21, nor between its elimination half-life on Days 1 and 21. Side-effects consisted mainly of fatigue and low-back pain on days of intense diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diuretic activity, safety and pharmacokinetics of torasemide during chronic treatment in normal subjects. 378 Aug 35

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