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

Various publications have described a beta 2-receptor regulated potassium transport system in the cellular membrane of human skeletal muscle. To examine the suggestion that serum potassium alterations are among the causes of premature muscular fatigue during physical exercise under pharmacological blockade of beta-receptors, we have compared the influence of sustained blockade with a beta 1-selective blocker and a nonselective beta-blocker on the levels of serum potassium before, during and after a physical exercise test. 63 healthy physical education students received in random order and under double blind conditions either 100 mg Metoprolol (beta 1-selective) or 80 mg Propranolol (non-selective), or placebo daily for 3 months. Serum potassium was measured before, during (at 150 Watt and at the end of exercise) and after a bicycle exercise with a stepwise increase in work loads. After three months of beta-blocker treatment serum potassium levels during exercise were significantly higher than in control subjects receiving the placebo, and it took longer for the serum potassium levels to return to the resting level in the beta-blocker treated subjects. At rest, however, the levels were not found to be statistically different. In the subjects receiving Propranolol the post-exercise serum potassium levels were higher than in the subjects receiving Metoprolol. Three days after cessation of the medication these differences were no longer perceptible. Our findings confirm the existence of a beta-receptor regulated potassium transport system in human skeletal muscle and indicate that the transmembranous potassium transport in human skeletal muscle is predominantly regulated via beta 2-receptors, although beta 1-receptors seem also to be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Physical performance and serum potassium under chronic beta-blockade. 299 86

We studied the effects of propranolol on respiratory muscle performance during inspiratory threshold-loaded endurance breathing in eight normal subjects. Propranolol (mean daily dose = 160 + 17 mg, SEM) reduced loaded 15-second MVV (92 versus 81 L/min;P = .01) and maximal sustainable ventilatory capacity (52.3 versus 44.5 L/min, P = .02) but did not affect the fraction of MVV, which was sustainable. Maximal static inspiratory pressures were reduced at two of three lung volumes, whereas maximal static expiratory pressures were unaffected by propranolol. The reduction in inspiratory muscle performance in the whole population could be accounted for almost entirely by four subjects who developed symptoms of "tiredness" and easy fatigability while receiving propranolol. There was no significant difference in propranolol dose, in degree of beta-receptor blockade, or in physical fitness in symptomatic and asymptomatic groups, and in neither group did propranolol alter pulmonary function test results. Propranolol directly depresses inspiratory muscle strength in subjects who develop drug-induced symptoms of fatigue by a mechanism probably unrelated to beta-adrenergic-receptor blockade.
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PMID:Propranolol and inspiratory muscle performance in normal subjects. 321 29

Oxygen utilization, arterial and venous blood gas levels, hemodynamic values and exercise tolerance were compared before and after administration of propranolol and verapamil in 10 patients with stable angina pectoris. During exercise, propranolol decreased cardiac output (CO) by 22%; O2 extraction was increased and O2 consumption (VO2) did not change. With verapamil treatment, CO modestly increased (7%), O2 extraction decreased and VO2 did not change. In contrast to O2 utilization, the drugs produced opposite changes in mixed venous and arterial blood gas levels. Propranolol decreased mixed venous pH, increased CO2 tension and decreased the pH of arterial blood. Verapamil increased venous pH and decreased CO2 tension; pH of arterial blood did not change. The drugs yielded similar levels of antianginal efficacy, but patients exercised longer during verapamil therapy and were less fatigued. The hemodynamic and metabolic differences suggest that muscle perfusion during exercise influences the onset of fatigue and may help determine the choice of therapy.
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PMID:Effect of propranolol and verapamil on oxygen utilization, acidosis and fatigue during exercise in stable angina pectoris. 361 85

The effect of selective and nonselective beta-adrenoceptor blockade on the thermoregulatory responses of 11 physically active, healthy, young adult men was studied during 2-hour block-stepping in heat. The trial consisted of 3 periods of 6 days each during which propranolol (160 mg/day), atenolol (100 mg) or matching placebo was administered in a randomized, double-blind crossover fashion. Propranolol and atenolol induced similar, significant (p less than 0.001) increases in subjective ratings of perceived exertion. The mechanism of this increased fatigue was not evident from the documented alterations in serum electrolyte, blood glucose and blood lactate levels or ventilatory parameters. Propranolol did, however, induce a postexercise delayed serum-potassium reversion. Although rectal and mean skin temperature responses were essentially unaltered by beta-adrenoceptor blockade during block-stepping, an increased total sweat loss was observed with propranolol (p less than 0.01 versus placebo) and to a lesser degree with atenolol (p = not significant versus placebo). This indicates that persons receiving beta-adrenoceptor blockers have an increased need to adhere to a strict fluid-replacement regimen during exercise. This potentially adverse response was minimal with atenolol in contrast to propranolol, and this in turn suggests the use of beta1-selective adrenoceptor blockers during prolonged exercise when adequate fluid replacement is not possible.
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PMID:Effect of selective and nonselective beta-adrenoceptor blockade on thermoregulation during prolonged exercise in heat. 399 52

All available beta-adrenergic blocking agents share the property of blocking beta 1 adrenoceptors, including those in the heart. They differ, however, in their ability to block beta 2 receptors (cardioselectivity), their membrane stabilizing action, intrinsic sympathomimetic activity and their pharmacokinetic properties. The strongest evidence for efficacy in secondary prevention has been obtained with timolol, metoprolol and propranolol. Timolol and propranolol block all beta-receptor-mediated responses and are therefore nonselective, whereas metoprolol is relatively cardioselective. Propranolol and metoprolol have membrane stabilizing action, but timolol does not; none of these agents show intrinsic sympathomimetic activity. Thus, no ancillary property is a requirement for efficacy. All of these agents may precipitate heart failure, but this problem has been exaggerated, and transient failure during the early course of myocardial infarction is no longer a contraindication to therapy. Cardioselective agents cause less bronchospasm, but this can still occur, especially with higher dosages. In addition, these agents probably cause somewhat less fatigue and result in less hypertension during hypoglycemia than nonselective agents. The availability of at least three effective agents allows for a choice of therapy to offer individual patients.
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PMID:Clinical pharmacology of the beta-blocking drugs: implications for the postinfarction patient. 613 42

The Beta-Blocker Heart Attack Trial was a multicenter, randomized, double-blind, placebo-controlled trial of propranolol therapy in 3837 men and women with acute myocardial infarction. The patients began their treatment 5-21 days after hospital admission (mean 13.8 days). During an average follow-up of 25 months, there were statistically significant reductions in total mortality (26%), cardiovascular mortality (26%), arteriosclerotic heart disease (27%), sudden death (28%) and coronary incidence (definite nonfatal reinfarction plus coronary heart disease mortality) (23%). There was no group difference in incidence of congestive heart failure. Of the many potential side effects that were monitored, broncho-spasm, cold hands and feet, and fatigue occurred more frequently in the propranolol group. Propranolol not only reduced coronary mortality and morbidity, but also was administered with a great degree of safety. Based on these results, its use is recommended for at least 3 years in patients with no contraindications to beta blockade who have had a recent myocardial infarction.
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PMID:Propranolol therapy in patients with acute myocardial infarction: the Beta-Blocker Heart Attack Trial. 634 40

The lipolytic response to fatigue-induced stress was studied in fed and fasted rabbits and in fed propranolol-treated rabbits. The initial plasma glycerol level was higher and the increase in glycerol after stress was lower in fasted as compared to fed animals. Propranolol lowered the initial glycerol level and attenuated the fatigue-induced rise in glycerol concentration. The data suggest that in rabbits, as in other species, catecholamines increase lipolysis through stimulation of beta-adrenoceptors. The increment in alpha-adrenergic responsiveness during fasting may contribute to decreased glycerol response to stress observed in fasted rabbits.
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PMID:Changes in plasma glycerol level in rabbits during fatigue-induced stress. 654 90

Propranolol, metoprolol, acebutolol, nadolol and atenolol were incubated with isolated rat skeletal muscle mitochondria at 30 degrees C, and the rate of oxygen consumption was measured with an oxygen microelectrode. The potency of these drugs to inhibit state III respiration was correlated with lipid solubility as measured by the octanol/water partition coefficient. The most lipid-soluble beta-blocker, propranolol, had an ED50 of 0.6 mmol/l. The most water-soluble one, atenolol, showed no inhibition at concentrations up to 16 mmol/l. Inhibition of respiratory control ratio, state IV respiration and ADP/O ratio occurred at 2 mmol/l for propranolol, 16 mmol/l for metoprolol and was not consistently observed for the other beta-blockers at the concentrations tested. The inhibition of state III respiration of skeletal muscle mitochondria by lipid-soluble beta-blockers may be one of the causes of the fatigue observed in some patients receiving these drugs.
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PMID:Lipophilic beta-blockers inhibit rat skeletal muscle mitochondrial respiration. 790 63

Propranolol, a nonselective beta-adrenergic blocking agent, although prescribed frequently, has not been monitored for its adverse reactions in Indian population. A collaborative ADR monitoring study was planned in 2661 hypertensive patients. Exclusion criteria were associated circulatory insufficiency, heart block, left ventricular failure, diabetic mellitus and airway obstruction. The incidence of ADR was 2.1%, which is lower than reported incidence of 8.7 to 43.7 percent in other studies. This could be attributed to improper selection of patients, differences in methodology of monitoring, or to racial variation. In the present study ADR of fatigue (1.1%), dizziness (0.4%) and headache (0.2%) constituted the bulk. Additional reaction of pain in chest (0.2%), heart block (0.1%), hypoglycemia (0.1%), loss of libido (0.1%) and shock (0.03%), were also observed.
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PMID:Adverse reactions to propranolol, a non-selective beta-adrenergic blocking agent in hypertensive patients--a collaborative study. 844 49

1. The effect of a beta-adrenoceptor antagonist, propranolol, was investigated on excitation-contraction coupling in small, intact bundles of soleus muscle fibres from the rat. 2. (+/-)-Propranolol significantly inhibited twitch and tetanic tension with IC50 values of 6.7 microM and 3.5 microM, respectively. 3. (+)-Propranolol (which has 100 times less beta-blocking activity than the (+/-) form) was approximately one third as effective as the (+/-) form at inhibiting isometric tension. 4. (+/-)-Propranolol (20 microM) had no significant effect on the amplitude of caffeine contractures, suggesting that it did not directly inhibit Ca2+ release from the sarcoplasmic reticulum. 5. The resting membrane potential measured after 15 min perfusion with 20 microM (+/-)-propranolol was not significantly different from control. However, this concentration of (+/-)-propranolol significantly reduced both the peak amplitude and the maximum rate of rise of the action potential. Both effects were only partially reversible after extensive washing. 6. (+/-)-Propranolol perfusion caused a modest reduction in the amplitude of sub-maximal K+ contractures at concentrations (5 microM) that markedly depressed tetanic tension. 7. The results indicate that (+/-)-propranolol can decrease isometric tension independently of beta-receptor occupation by (i) reducing the amplitude and rate of rise of the action potential and (ii) by directly inhibiting excitation-contraction coupling. The relatively low IC50 for the 'membrane-stabilizing' action of propranolol on tetanic tension (3.5 microM), combined with the ability of the drug to accumulate gradually in biological membranes, may contribute to a peripheral component of the tremorolytic and fatigue-inducing actions of propranolol on skeletal muscle.
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PMID:Inhibitory effects of (+/-)-propranolol on excitation-contraction coupling in isolated soleus muscles of the rat. 935 2


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