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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients treated with beta-blocking agents often complain of fatigue during exercise. Exercise capacity is decreased under this condition. Nebivolol is a new beta 1-adrenoceptor antagonist with a particular hemodynamic profile, which might be due to an ancillary property. Five milligrams once daily seems the optimal dose for antihypertensive treatment. In a double-blind, placebo-controlled crossover study, the effects of nebivolol on maximal and endurance exercise capacity are compared with those of atenolol in healthy volunteers. The hemodynamic and metabolic effects during exercise are also studied. Nebivolol 5 mg once daily and atenolol 100 mg once daily decrease blood pressure at rest similarly. At these dosages nebivolol shows a smaller decrease in heart rate than atenolol. During exercise, the rise in systolic blood pressure and heart rate is less depressed with nebivolol than with atenolol. In contrast to atenolol, nebivolol does not decrease maximal and endurance exercise capacity, and does not increase perceived exertion significantly. Changes in hemodynamics influence maximal exercise capacity. Since nebivolol has less effect on exercise hemodynamics than atenolol, this might explain why maximal work capacity is not changed during nebivolol. During endurance exercise metabolic effects are thought to be more important. Under nebivolol glycerol and NEFA production is less depressed during exercise and might explain the preserved endurance capacity. These data suggest less beta blockade during nebivolol than during atenolol at the dosages used in this study. In conclusion, at a dose known to be antihypertensive, nebivolol does not alter exercise capacity significantly in healthy volunteers.
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PMID:Exercise tolerance with nebivolol and atenolol. 135 67

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.
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PMID:Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease. 137 20

beta-Blockers are known to suppress exercise-induced ischemia but give rise to such problems as fatigue or dyspnea on effort and also bradycardia. In a series of double-blind, placebo-controlled studies of celiprolol (a cardioselective beta 1-blocker with beta 2-agonist and vasodilatory properties) in patients with hypertension and angina and in normal volunteers, it was found that celiprolol did not produce bradycardia when given in combination with verapamil. Celiprolol did reduce exercise-induced ischemia, but there was no reduction in cardiac output at rest or on exercise compared with placebo. Compared with atenolol, celiprolol produced less dyspnea and fatigue at submaximal levels of exercise. It is concluded that celiprolol possesses certain differences, compared with conventional beta-blockers, that may be of direct clinical benefit.
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PMID:Angina, ischemia, and effort tolerance with vasodilating beta-blockers. 167 26

beta-Adrenoceptor blockers are widely used clinically and can be classified as nonselective (beta 1 and beta 2) or selective (beta 1). Impairment of exercise performance is a well-known side effect of this group of drugs. This paper reviews mechanisms that could potentially be responsible for this impairment. In addition to cardiovascular and metabolic effects, beta-blockade inhibits Na(+)-K+ ATPase pumps controlling ion movement between muscle and plasma and thus may contribute to muscle fatigue through this mechanism. To investigate the relationship between the change in plasma [K+] and exercise performance, we studied healthy male subjects taking propranolol. Eight subjects performed maximal incremental cycle ergometer exercise tests during control (no drug), low dose (LD) (40 mg daily), and high dose (HD) (265 +/- 4.3 (SE) mg daily) of propranolol. The control plasma [K+] (5.8 +/- 0.12 mequiv./L) during exercise was significantly lower than either the LD (6.4 +/- 0.05 mequiv./L) or HD (6.1 +/- 0.16 mequiv./L) values. There was no significant difference between plasma [K+] for the LD and HD of propranolol. However, maximum oxygen uptake was reduced only while taking the HD of propranolol. Six of the subjects also performed three 30-s bouts of high intensity exercise on an isokinetic cycle ergometer while taking the LD and HD of propranolol. There was no significant difference between doses for the increase in plasma [K+] (LD, 7.8 +/- 0.35 mequiv./L vs. HD, 7.6 +/- 0.36 mequiv./L) during exercise. However, exercise performance was significantly reduced during HD compared with LD. These results suggest that the increases in plasma [K+] with propranolol did not play a direct significant role in the reduced performance observed during the HD.
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PMID:Factors contributing to increased muscle fatigue with beta-blockers. 167 29

1. The differential effects of beta-adrenoceptor subtypes on potassium fluxes and exercise capacity were compared in eight healthy young men using single oral doses of the selective beta 2-adrenoceptor antagonist ICI-118551, the selective beta 1-adrenoceptor antagonist atenolol or the non-selective beta-adrenoceptor antagonist propranolol. The study was randomized, double-blind and placebo controlled. 2. Potassium in the venous effluent from the exercising muscles increased progressively with increasing exercise intensity. This response was augmented by propranolol, whereas neither atenolol nor ICI-118551 modified the response. After exercise potassium concentration fell exponentially with no difference between the treatment regimens. 3. Cumulative work was significantly reduced by ICI-118551 (6.4%, P = 0.04) and by propranolol (12.4%, P less than 0.01), whereas the reduction with atenolol (5.6%) did not reach statistical significance. 4. Atenolol and propranolol reduced peak heart rate by 23% and 29%, and peak systolic blood pressure by 9% and 11% respectively during maximal exercise. ICI-118551 caused a non-significant reduction in heart rate during submaximal exercise, with a significant reduction at maximum exercise (6% reduction), whereas systolic blood pressure was not different from placebo. Diastolic blood pressures were similar across all treatment regimens. 5. Similar glucose concentrations were obtained at baseline and at exhaustion during all treatment regimens. Lactate concentrations were comparable for any given exercise intensity irrespective of treatment regimens. Propranolol reduced lactate concentrations from the exercising muscles at maximum exercise in proportion to the reduction of maximal exercise capacity. 6. The subjective perception of fatigue was not affected by either beta 1- or beta 2-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of selective beta 2-adrenoceptor blockade on serum potassium and exercise performance in normal men. 168 47

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 effects on exercise tolerance of 7-day treatment with a calcium channel blocker, verapamil 160 mg twice daily (b.i.d.), and a beta 1-selective blocker, atenolol 50 mg b.i.d., were compared in 10 healthy and physically active young subjects in 5,000-m cross-country running at high intensity. The study was a double-blind cross-over trial. Comparison was made with a single-blind placebo as well. Performance time was measured every 1,000 m in seven 5,000-m runs, in which subjects were instructed to keep to a constant fatigue perception (Borg scale rating). Both drugs significantly (p = 0.001) increased the performance time over the first 1,000 m as compared with placebo. However, running time after 1,000, 2,000, and 3,000 m was prolonged significantly less (p less than 0.05) by verapamil than by atenolol. For the entire 5,000-m run, atenolol caused a significant increase (p = 0.001) in mean running time by 1 min 34 s (i.e., 7.5%; 95% confidence interval 48 s to 2 min 21 s) as compared with placebo, whereas verapamil caused no significant change (+46 s).
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PMID:Effects of verapamil and atenolol on exercise tolerance in 5,000 m cross-country running: a double-blind cross-over study in normal humans. 169 62

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

Beta-blockers reduce physical capacity and lead to an increased sensation of muscular fatigue. The limits of endurance capacity, which is important for both leisure-sports and fitness, are set primarily by metabolic factors, because the energy liberation via the metabolism of lipids and carbohydrates is reduced as a result of the inhibition of lipolysis and glycogenolysis. Beta 1-selective blockers influence the physical capacity less effectively on any intensity level as non-selective blockers do. The latter may lead to hypoglycemic reactions. Beta-blockers with intrinsic sympathicomimetic activity (ISA) are not superior to others. Physically active patients should be treated with beta 1-selective blockers.
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PMID:[How do beta receptor blockers modify physical performance and metabolism?]. 197 80

beta-receptor antagonists have for many years been considered appropriate alternatives in the primary management of mild to moderate hypertension. Generally, they have been shown to be safe with a low frequency of serious side-effects. Among the predictable and usually doserelated side-effects are bradycardia, bronchospasm, hypotension, muscle fatigue and cold extremities. Examples of unexpected side-effects are gastrointestinal symptoms such as nausea and disturbed intestinal motility, skin reactions, sexual dysfunction, as well as effects related to the central nervous system (CNS) such as emotional disturbances. The CNS-related side-effects, the mechanisms of which are unclear, consist of subtle effects on general well-being, decreased initiative, a depressed frame of mind and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. Thus, all beta-blockers on the market seem to have high benefit-risk ratio, but independent of their physiochemical properties and pharmacodynamic profile, they seem to cause side-effects to about the same extent. The results so far available have been obtained by primarily using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side-effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quality of life/subjective symptoms during beta-blocker treatment. 198 27


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