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)

Beta-blockade is known to induce muscle fatigue and tendency to hypoglycaemia during prolonged exercise. In addition, beta-blocking agents influence the secretion of many hormones, which regulate glucose. We have investigated the effects of a beta 1-selective (metoprolol) and a non-selective (propranolol) beta-blocking agent on muscle glycogenolysis, blood glucose and lactate levels, plasma levels of free fatty acids and on secretion of insulin, growth hormone, glucagon and cortisol during physical exercise in a double blind cross-over study in seven healthy male volunteers. They participated in three bicycle ergometer tests each lasting for 30 minutes under treatment of placebo (C), metoprolol (M) or propranolol (P). A biopsy was obtained from the vastus lateralis muscle before and immediately after the exercise for muscle glycogen assay. The glycogen concentration after exercise tended to be lower in C than in M or P experiment. The blood glucose level decreased during P and at 30 min there was a significant difference between P and C. The blood lactate was significantly lower before exercise during P than C or M. The increase of blood lactate during exercise, however, was not inhibited by P. Both beta-blocking agents counteracted the increase of FFA during exercise. There was a marked increase of growth hormone secretion during beta-blockade. The secretion of glucagon and cortisol were slightly increased by P and M, but the plasma insulin level was not affected by beta-blockade.
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PMID:Modification of the metabolic and hormonal response to physical exercise by beta-blocking agents. 675 73

Thirty-two patients with primary hypertension were studied in a double-blind cross-over comparison between the cardioselective beta 1-blocking agent atenolol and the combined alpha- and beta-blocking agent labetalol. The doses used were atenolol 50--150 mg twice daily and labetalol 200--600 mg twice daily. Both drugs effectively reduced blood pressure and heart rate. Dose increments every second week resulted in a higher proportion of patients with normal blood pressure (les than or equal to 150/90 mm Hg) with both drugs. Labetalol was somewhat more effective in lowering upright blood pressure while atenolol caused a more pronounced heart-rate reduction. Both agents decreased plasma renin activity and urinary aldosterone excretion. Scalp tingling on labetalol (2 patients) and cold fingers with atenolol (1 patient) caused withdrawal of the drugs. Cold fingers were reported in another four patients during treatment with atenolol and in one when on labetalol. Tiredness and postural symptoms were more common during intake of labetalol.
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PMID:Antihypertensive and metabolic effects of increasing doses of atenolol and labetalol. A comparative study in primary hypertension. 676 Jun 79

Thirty patients with stable angina have been undergone a multistage treadmill test, after a single oral dose of 100 mg of Atenolol, a beta 1 . selective blocking agent, in comparison to a previous test carried out after an identical looking placebo tablet. After placebo all the patients showed ischemic ST segment response (ST depression greater than 1 mm), 25 of them interrupting the test because of anginal pain (20 patients), or of ST depression greater than 3 mm (3 patients), or of ventricular ectopics (one patient), or of fatigue (one patient). After Atenolol 10 patients completed the planned test, 7 of them without ischemic changes of ST. 27 patients (90%) showed increased working capacity with significant reduction of heart-rate (FC), systolic blood pressure (PAS) and their product and of ST depression, either before and during and at the end of exercise. The recovery time of ischemic ECG change has been significantly reduced. The observed increased working capacity is attributed to the reduced myocardial O2 consumption expressed from the reduction of the product FC x PAS. Nevertheless at the end of exercise test after beta-blocking drug this product didn't reach the threshold value at which the test was interrupted in the first test after placebo. The authors discuss the possible cause of this effect of beta-blocking drugs, which could be attributed to a reduction of coronary blood flow and/or to an increased myocardial tension because of increased end diastolic ventricular volume. However the Authors outline that the per cent increases of FC, PAS, and FC x PAS have not been reduced by the Atenolol, unlike their absolute values, at the threshold of angina: the ischemic reveals itself at same levels of per cent increase of the factors of O2 myocardial consumption, the later reaching of threshold values depending on the lower starting values. The advantages of Atenolol as regards the other beta-blocking drugs (better acceptability, stability and duration of action) are outlined too.
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PMID:[Evaluation by exercise test of effects of a single oral dose of atenolol in patients with stable angina (author's transl)]. 704 18

There is growing evidence that the amyloid beta-peptide (beta 1-40) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta 1-40 has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether beta 1-40 (or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2 h and 4 h at 37 degrees C together with 6 mumol L-1 of beta 1-40 or of fragments beta 1-28 and beta 25-35, resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05 mumol L-1). Moreover, beta 1-40 and its two fragments induced a significant alteration of 45Ca permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of beta 1-40 and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca(2+)-ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanism in Alzheimer's disease.
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PMID:Alzheimer amyloid beta-peptides exhibit ionophore-like properties in human erythrocytes. 755 64

Amphetamine, caffeine, sydnocarb, meclofenoxate, adapromine, midantan, and nomifensine were studied for their effects on bioelectrical activity and Fourier EEG power spectra of the sensomotor cortex, dorsal hippocamp and lateral hypothalamus of freely behaving awake rats. The drop in the absolute power of all frequency ranges with the enhanced power of fast beta 1,2-ranges was common to the action of psychostimulants. In addition to the common properties, specific features of their action were revealed. Amphetamine, meclofenoxate, and nomifensine were found to increase the amplitude of the dominant peak in the theta-range and amphetamine shifts the frequency of the dominant peak to the region of faster ranges. The agents-induced electrophysiological changes correspond to the varying degrees of activation of the central nervous system, causing the optimization of behavioral functions, abolition of fatigue and drowsiness and enhancing physical and mental working capacity.
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PMID:[Comparative quantitative pharmacological-EEG analysis of the effects of psychostimulants]. 762

Celiprolol is a novel beta 1 selective adrenoreceptor blocker with partial beta 2 agonism and direct vasodilator activity. These ancillary properties may reduce symptomatic breathlessness and fatigue and modify respiration during exercise. To test this hypothesis 20 men with stable effort angina were enrolled in a double-blind crossover study to investigate the effects of atenolol 100 mg once daily (A) and celiprolol 400 mg once daily (C) on cardiorespiratory and symptomatic variables during maximal and submaximal exercise. Total exercise time on a modified Bruce protocol was similar on both treatments: C12.5 min, A 13.1 min. During steady state submaximal exercise at 60-75% (mean 68%) of maximum work capacity, minute ventilation (C33.81 min-1, A 33.51 min-1), oxygen uptake (C14.6 ml.kg-1.min-1, A15.1 ml.kg-1.min-1), respiratory exchange ratio (C 0.89, A 0.87), ratio of VE/VCO2 (C 33.6, A 33.4), ratio of VE/VO2 (C 2.34, A 2.72), Borg perceived exertion score (C 11.2, A 10.9) and visual analogue scores for breathlessness (C 29.5, A 25.9) and muscle fatigue (C 28.9, A 26.0) were all similar on both treatments. At maximal exercise capacity on the modified Bruce protocol, minute ventilation (C 58.31 min-1, A 60.41 min-1), oxygen uptake (C 21.3 ml.kg-1.min-1, A 21.7 ml.kg-1.min-1), respiratory exchange ratio (C 1.02, A.1.05), ratio VE/VCO2 (C 34.8, A 35.9), and ratio VE/VO2 (C 2.80, A 2.83) were also similar on both drugs. Over a 10 day period anginal attacks (C 10.1 +/- 10.4, A 5.4 +/- 5.9) and sublingual GTN use (C 5.9 +/- 10.3, A 4.4 +/- 9.8) were both more frequent on celiprolol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiorespiratory and symptomatic variables during maximal and submaximal exercise in men with stable effort angina: a comparison of atenolol and celiprolol. 783 73

1. Exercise and beta-adrenoceptor blockade have important roles in the prevention and treatment of cardiovascular disease, but fatigue and a reduced capacity to exercise are commonly reported side effects of beta-adrenoceptor blockers. The reduced capacity to exercise may be partly caused by a reduction in fat metabolism. 2. We investigated the effects of atenolol 50 mg, metoprolol CR/Z0K 50 mg, metoprolol CR/Z0K 100 mg and placebo, on heart rate, energy expenditure, fat oxidation, plasma free fatty acids, glycerol, glucose, lactate, ammonia and perceived exertion during 2 h of treadmill walking at 40% of maximal oxygen uptake in 20 healthy volunteers. 3. Compared with placebo (38.0%), total fat oxidation was significantly lower on atenolol 50 mg (30.1%) and metoprolol CR/Z0K 100 mg (31.0%), but not on metoprolol CR/Z0K 50 mg (33.7%). Reductions in fat oxidation correlated well (r2 = 0.970) with reductions in exercising heart rate, and probably reflected the degree of beta 1-adrenoceptor blockade. Maximum plasma ammonia concentration was reached after 45 min of exercise on atenolol, 60 min on metoprolol CR/Z0K 100, and 75 min on metoprolol CR/Z0K 50, and was higher than placebo on all active drug treatments. 4. The greater reduction in fat oxidation with atenolol may be a reflection of a peak in plasma concentration, which is avoided with a controlled release preparation.
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PMID:Exercise metabolism in healthy volunteers taking atenolol, high and low doses of metoprolol CR/Z0K, and placebo. 788 87

The effects of beta-blockade on skeletal muscle excitability and fatiguability during exercise were examined. Ten healthy males (mean age 21.9 +/- 1.1 yr) performed a 4-min fatigue protocol consisting of intermittent isometric voluntary contractions of the knee extensors in one leg. Subjects performed the exercise after treatment with placebo, 100 mg metoprolol, or an equipotent dose of propranolol (60 mg, n = 1; 80 mg, n = 8; 100 mg, n = 1) twice a day for 76 h before testing according to a randomized double-blind design. The evoked twitch torque, maximal voluntary torque, and maximal M-wave amplitude were unaffected by the beta-blockade treatments before fatigue. During the placebo trial, there were significant reductions in the evoked and voluntary torques (77 +/- 15 and 55 +/- 11%, respectively) after the fatigue protocol; however, both the voluntary electromyogram and evoked M waves were well maintained throughout fatigue. The beta-blockade treatments had no significant effect on torque or electromyogram activity over the course of the exercise. Thus, despite evidence for an impairment of dynamic exercise performance with beta 1- and beta 1,2-blockade, there appears to be no effect of these agents on muscle excitability and fatiguability during isometric muscle activity.
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PMID:Effect of selective and nonselective beta-blockade on skeletal muscle excitability and fatiguability. 792 71

Fibromyalgia, a chronic condition of widespread pain, stiffness, and fatigue, has proven unresponsive to drugs, the use of which is based on the 'serotonin-deficiency hypothesis'. An alternative hypothesis-failed transcription regulation by thyroid hormone-can explain the serotonin deficiency and other objective findings and symptoms of euthyroid fibromyalgia. Virtually every feature of fibromyalgia corresponds to signs or symptoms associated with failed transcription regulation by thyroid hormone. In hypothyroid fibromyalgia, failed transcription regulation would result from thyroid-hormone deficiency. In euthyroid fibromyalgia, failed transcription regulation may result from low-affinity thyroid hormone receptors coded by a mutated c-erbA beta 1 gene, yielding partial peripheral resistance to thyroid hormone. The hypothesis of this paper is that, in euthyroid fibromyalgia, a mutant c-erbA beta 1 gene (or alternately, the c-erbA alpha 1 gene) results in low-affinity thyroid-hormone receptors that prevent normal thyroid hormone regulation of transcription. As in hypothyroidism, this would cause a shift toward alpha-adrenergic dominance and increases in both cyclic adenosine 3'-5'-phosphate phosphodiesterase and inhibitory Gi proteins. The result would be tissue-specific hypothyroid-like symptoms despite normal circulating thyroid-hormone levels.
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PMID:Mutations in the c-erbA beta 1 gene: do they underlie euthyroid fibromyalgia? 907 94

The aim of this paper was to examine if there were clinical studies supporting a beneficial effect of an even plasma concentration over 24 h for the most frequently prescribed beta 1-blockers in clinical practice, metoprolol CR/ZOK and atenolol. There are several studies showing that metoprolol CR/ZOK has a more even plasma concentration compared with atenolol and conventional metoprolol tablets when administered once daily. There are also studies showing that metoprolol CR/ZOK produces a more even beta 1-blockade over 24 h. This is determined by expressing the percentage reduction in exercise heart rate in relation to placebo at intervals throughout the 24-h period and comparing the results with those of atenolol and conventional metoprolol tablets. Clinical studies indicate that the low peak plasma concentration produced by metoprolol CR/ZOK leads to more beta 1 selectivity than atenolol and conventional metoprolol tablets. The loss of beta 1 selectivity at peak plasma concentrations may cause unwanted side-effects. The peak plasma concentration of atenolol coincides with increased general and leg fatigue, problems less evident when patients are on metoprolol CR/ZOK. The frequency and severity of other central nervous system related side-effects are comparable with metoprolol CR/ZOK and atenolol. In conclusion, there are several clinical studies supporting a beneficial effect of the even plasma concentration over 24 h achieved with metoprolol CR/ZOK.
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PMID:Treatment with beta-blockers--the value of an even plasma concentration over 24 h. 944 71


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