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)

The influence of clinical doses of drugs that affect beta-adrenoceptors has been examined on heart rate, blood pressure, duration of exercise, and on electrolyte concentrations (Na, K, Ca and Mg) during recovery from exercise in healthy volunteers. The drugs used were a beta 1-adrenoceptor antagonist atenolol, a nonselective beta-adrenoceptor antagonist propranolol, and a cardioselective, partial beta 1-adrenoceptor agonist with 43% ISA activity, xamoterol. The duration of exercise was smaller on propranolol. Maximum exercise heart rate and blood pressure were reduced significantly by propranolol and atenolol. Xamoterol reduced maximum exercise heart rate and had no effect on blood pressure. The degree of breathlessness and fatigue revealed no differences between treatments. Recent evidence has suggested an association between hyperkalaemia and hypomagnesaemia with an increase in the occurrence of arrythmias following acute myocardial infarction. Exercise-induced hyperkalaemia has been suggested as a factor in sudden death. The results confirmed a rise in serum potassium during exercise and attenuation of the fall during recovery under beta-adrenoceptor blockade. Xamoterol was no different from placebo in these respects. Exercise also produced a rise in magnesium levels and during recovery the level fell below baseline. Both these effects were attenuated by propranolol. Calcium levels were not affected by any of the treatments.
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PMID:Comparison of the effects of xamoterol, atenolol and propranolol on breathlessness, fatigue and plasma electrolytes during exercise in healthy volunteers. 168 93

The sympathetic nervous system becomes activated in heart failure, and while this is initially beneficial, the consequences of prolonged raised levels of catecholamines can be counterproductive. Xamoterol, a partial agonist that acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18%. The xamoterol group also showed significant improvements in symptoms of breathlessness, fatigue, and life values as compared with the placebo group. In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of clinical experience with xamoterol. Effects on exercise capacity and symptoms in heart failure. 196 61

1. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587), a beta 1-adrenoceptor partial agonist, improves both systolic and diastolic function in heart failure patients. 2. Double-blind, randomised studies comparing xamoterol with placebo showed that the beneficial haemodynamic effects of xamoterol produced significant improvements in exercise capacity and symptoms in patients with mild to moderate heart failure. These studies formed the basis for a large European multicentre study programme which recruited over 1000 patients, randomised to xamoterol (200 mg twice daily, n = 617), digoxin (0.125 mg twice daily, n = 135) or placebo (n = 300) for 3 months. 3. Efficacy was assessed by measuring exercise capacity and symptoms. The xamoterol group improved exercise capacity by 37% compared with an 18% improvement in the placebo group. Differences in the symptom scores measured by visual analogue scales and Likert scores indicated significant improvements by xamoterol in the cardinal symptoms of heart failure, dyspnoea and fatigue. 4. Analyses of data from subsets of patients in the study showed that elderly patients, patients on no other heart failure therapy and patients with cardiomegaly all had similar improvements in exercise and symptoms to those seen in the whole study population. In the subset which included digoxin treatment, xamoterol produced significantly greater improvements in exercise capacity than digoxin (33% vs 17%, P less than 0.05) and was associated with fewer side-effects. 5. Xamoterol is therefore a promising addition to heart failure therapies currently available.
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PMID:Xamoterol, a beta 1-adrenoceptor partial agonist: review of the clinical efficacy in heart failure. 257 51

The clinical efficacy of xamoterol, alpha beta 1-adrenoceptor partial agonist, was determined in a multicentre double-blind, randomized, parallel group study of 240 patients with mild to moderate heart failure. At entry, 62% of patients were receiving diuretics (thiazides, or loop diuretics at a dose no greater than the equivalent of 80 mg of frusemide); 32% were taking nitrate formulations and 14% digoxin for control of atrial fibrillation. Assessments were carried out after a 1-week placebo run-in and after 3 months of treatment with either xamoterol or placebo. 198 patients completed the study of whom 186 had valid exercise tests. Mean exercise duration increased by 7% after placebo and by 19% after xamoterol during a progressive treadmill exercise protocol. Xamoterol significantly reduced peak exercise heart rate compared with placebo. Subjectively, there was improvement in breathlessness on the visual analogue scale after treatment with xamoterol compared with placebo, but no change in fatigue. We conclude that xamoterol produces sustained improvement in symptoms and exercise duration in mild to moderate heart failure.
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PMID:Clinical efficacy of xamoterol, a beta 1-adrenoceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group. 257 8