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)

A double-blind multicentre study of 349 hypertensive patients was performed to compare the side-effects of the two beta-blockers atenolol (selective beta 1-blocker) and pindolol (beta 1- and beta 2-blocker with Intrinsic sympathomimetic activity (ISA] in equipotential doses (100 mg atenolol vs. 15 mg pindolol). Male and female patients aged 20-65 years with essential hypertension WHO stages I and II were included. Patients were examined 1 and 6 months after the start of treatment, and side-effects were recorded. The antihypertensive effect was similar for the two drugs. After 1 month there was significantly less bradycardia (P less than 0.01), cold hands and feet (P less than 0.05) and tiredness (P less than 0.02) in the pindolol group, and less sleep disturbance (P less than 0.02) in the atenolol group. After 6 months there was no significant difference in sleep disturbance, but the differences in the other side-effects remained significant.
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PMID:Comparison of the side-effects of pindolol and atenolol in the treatment of hypertension. 220 4

In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2-4 h. All three active treatments produced significant beta 1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of beta 1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
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PMID:Subjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects--a comparison with atenolol. 237 31

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

Training bradycardia during autonomic blockade has been studied in rats and humans. The heart rate after autonomic blockade (intrinsic heart rate) is also lowered as a part of the adaptation to training. However, this nonautonomic component of the cardiac adaptation requires a long duration of intense endurance training to appear. This is in contrast to the autonomic component of the training bradycardia. From animal studies we have concluded that even if the training bradycardia is due to an adaptation within the heart itself, the adrenergic nerves are important for the development of a slow intrinsic heart rate. Neither the beta-receptor stimulation nor the degree of the heart rate increase during exercise is the main stimulus for the development of a training-induced bradycardia. Well-trained bicyclists had an intrinsic heart rate 20 beats lower than untrained normal control subjects. The heart rate at rest and the maximal heart rate were also on an average 20 beats lower for the bicyclists. There was no significant difference between propranolol and the beta 1 selective metoprolol in this study regarding their effects on heart rate and on deterioration of the maximal oxygen consumption after blockade. This deterioration was more marked in the well-trained than in the sedentary group. Based upon studies both in normal subjects and patients a careful rating of symptoms including physical exertion, fatigue or pain in the legs, dyspnea and chest pain using a Borg scale is recommended during exercise testing with beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects and adverse effects of autonomic blockade in physical exercise. 285 91

Beta adrenoceptor antagonists are effective in the symptomatic management of angina pectoris. This paper examines critically the possible influence of the ancillary properties of beta 1 selectivity, partial agonism and membrane-stabilizing action on the response in anginal patients. The response is categorized according to experimental, pharmacological and clinical endpoints, placing emphasis on the possible errors which may arise from extrapolation from the former to the latter. It is concluded: That selective beta adrenoceptor antagonism confers limited, but tangible advantages over non-selective antagonists in regard to patients with reversible airways obstruction, and also in the metabolic and haemodynamic response to acute hypoglycaemia. Cardioselectivity does not influence the central haemodynamic response to exercise, but lessens adrenaline-mediated hypertensive responses to smoking and hypoglycaemia. Non-selective partial agonists cause less reduction in resting ventricular function, but their effects on cardiac output during exercise are indistinguishable from full antagonists. Membrane stabilizing properties have a marked influence on the tolerability of these agents in terms of unwanted, nonspecific central nervous system symptoms. Unresolved questions relate to the influence of partial agonism on fatigue, metabolic responses, especially blood lipids and glucose, and the possibility of lesser efficacy in angina compared to full antagonists.
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PMID:The possible role of the ancillary properties of beta adrenoceptor antagonists in the management of angina pectoris. 286 Jul 71

beta-Adrenoceptor blockers (beta-blockers) are common first-choice drugs in the treatment of various cardiovascular disorders. Physical exercise performed during single-dose administration of beta-blockers, however, is associated with an increased rate of perceived exertion; an effect which appears to be partly reduced with long term treatment. Although clinical doses of beta-blockade may reduce heart rate by 30 to 35%, during maximal exercise cardiac output is not equally reduced. Accordingly, most studies have demonstrated increased stroke volume after beta-blockade. This reduction in heart rate is typically accompanied by a decreased VO2max (5 to 15%) in both patients and healthy, trained subjects. This smaller reduction in VO2max, as compared with the decrease in cardiac output, is the result of a partly compensating increased arteriovenous O2 difference. Work capacity as reflected by the ability to perform intense short term or more prolonged steady-state exercise is also impaired following beta-blockade. beta-Adrenoceptors can be subdivided into types beta 1- and beta 2. Blockers which are specific for either beta 1-receptors (beta 1-selective blockers) or both beta 1- and beta 2 receptors (non-selective blockers) differ with regard to their effect on exercise performance. Exercise performance ability, irrespective of exercise intensity and duration, is impaired to a greater extent following non-selective than beta 1-selective blockade at equal reductions in heart rate. This response stems from a decreased energy flux through glycogenolysis during non-selective blockade treatment. Individuals receiving beta-blockade medication therefore show greater adaptive response to physical conditioning during treatment with beta 1-selective than non-selective blockade probably because of greater training intensity with the former therapy. Neither psychomotor performance nor muscular strength and power is negatively affected by beta-blockade. Nevertheless, the ability to perform athletic events requiring high levels of motor control under emotional stress but not high levels of aerobic or anaerobic energy release, is probably increased during beta-blockade.
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PMID:Exercise performance and beta-blockade. 286 77

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse reactions and interactions with beta-adrenoceptor blocking drugs. 287 46

The antihypertensive efficacy of bevantolol, a selective beta 1-adrenoreceptor antagonist, was evaluated in 17 patients with essential hypertension, using continuous ambulatory intraarterial blood pressure (BP) monitoring. The study compared a twice-daily regimen (titrated dose of 200 to 600 mg/day) with the same amount given in a single daily dose. Within-patient comparisons of mean hourly systolic and diastolic BPs and heart rate showed a highly significant effect with twice-daily therapy (p less than 0.001) for all of the 24 hours. Similar significant results were obtained with a single morning dose. There was no difference between the pattern or extent of BP reduction with the 2 regimens. The decrease in BP after bevantolol persisted during the physiologic tests (rest, tilt, isometric and dynamic exercise). Four patients developed minor side effects with the single morning dose, and only 1 patient with the twice-daily regimen. These effects included tiredness, fatigue and dizziness. Unlike pure beta-blocking agents, bevantolol controlled the early morning increase in BP, lending support to the belief that it possesses vasodilatory properties in addition to beta blockade. These results suggest that bevantolol may be useful as first-line therapy in a once-daily dosage for the treatment of essential hypertension.
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PMID:Once- and twice-daily bevantolol for systemic hypertension using 24-hour ambulatory intraarterial blood pressure recording. 287 95

Adverse effects of beta-adrenergic receptor blocking drugs can be divided into two categories: 1) those that result from known pharmacological consequences of beta-adrenergic receptor blockade; and 2) other reactions that do not appear to result from beta-adrenergic receptor blockade. Adverse effects of the first type include bronchospasm, heart failure, prolonged hypoglycemia, bradycardia, heart block, intermittent claudication, and Raynaud's phenomenon. Neurological reactions include depression, fatigue, and nightmares. It is not yet proven whether the beta 1-selective adrenergic blockers or those with partial agonist activity reduce the overall frequency of adverse reactions seen with propranolol. Patient age does not appear, in itself, to be associated with more beta-blocker side effects. Side effects of the second category are rare. They include an unusual oculomucocutaneous reaction and the possibility of oncogenesis. There are also many drugs that interact with beta-blockers, which may increase toxicity. Finally, there are specific patient characteristics where one beta-blocker may be more effective and safer than another.
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PMID:Beta-adrenergic receptor blockers. Adverse effects and drug interactions. 289 72


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