Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classic renal tubular acidosis is characterized by a primary defect in establishment of a large hydrogen ion gradient across the distal renal tubule. Thus the development of hyperchlorenic metabolic acidosis follows. In addition, hypokalemia results from renal potassium wasting secondary hyperaldosteronism from sodium wasting and contraction of the extracellular fluid. The presenting signs and symptoms are growth retardation, fatigue, periodic paralysis, polyuria, polydipsia, vomiting and constipation as well as nephrocalcinosis and nephrolithiasis. It is suggested that effective treatment with alkali therapy requires markedly higher doses than formerly recommended, and may related to a higher rate of endogenous acid production from (1) intermediary metabolism of sulfur amino acids and organic acids, (2) impaired tubular reabsorption of bicarbonate and (3) hydrogen ion release from hydroxyapatite formation. It is also suggested that acidosis may interfere with vitamin D metabolism and thus play an important role in the pathoetiology of the growth failure in children with this disorder.
 ...
PMID:Acid-base, calcium, potassium and aldosterone metabolism in renal tubular acidosis. 3 60

Valproic acid is a new antiepileptic drug. It has a marked effect on generalized spike-wave discharges. The exact mechanism of action is uncertain; however, some evidence suggests an effect on the metabolism of gamma-aminobutyric acid. It is rapidly absorbed from the gastrointestinal (GI) tract. Concurrent administration with phenobarbital may result in elevated phenobarbital plasma concentrations. Administration with phenytoin sodium may transiently result in lower total phenytoin plasma levels. Side effects are generally mild and include fatigue, GI disturbances, weight gain, a fine postural and resting tremor, mild thrombocytopenia, and an increase in hepatic enzymes. Platelet counts and liver function monitoring should be done during valproic acid therapy. Drowsiness may be seen in patients receiving other antiepileptic drugs concurrently.
 ...
PMID:Valproic acid. Review of a new antiepileptic drug. 11 Feb 94

Electrophysiologic, morphologic, and biochemical definitions of the synapse will be correlated spatially and temporally. Postsynaptic fatigue and facilitation follow oscillations of the free pool of acetylcholine, predicted by the kinetic theory and observed at the electric organ of Torpedo marmorata. The underlying thermodynamic instability exhibits properties of the Na+--K+-dependent hydrolysis of adenosine triphosphate and represents a necessary condition for synaptic memory.
 ...
PMID:On the kinetics of acetylcholine at the synapse. 14 69

The action of sodium oxybutyrate, phenamine transamine and L-DOPA on the processes of re-establishing the mental and physical performance capacity after fatigue was studied in experiments with rats. The activating effect of sodium oxybutyrate on the resotration of performance capacity in these conditions is shown not to be inferior to an analogous action of phenamine. Complete re-establishment of performance capacity is recorded against the background of the action produced by a monoaminoxidase inhibitor-transamine, as well as combinations of sodium oxybutyrate and L-DOPA.
 ...
PMID:[Effect of sodium oxybutyrate, phenamin, transamine and L-dopa on the processes of work capacity recovery under conditions of minimal rest]. 24 61

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
 ...
PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.
 ...
PMID:[Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)]. 35 72

In a double-blind crossover trial conducted on a multicentre basis, 109 patients with "classic" or "definite" rheumatoid arthritis were treated for two weeks with diclofenac sodium (Voltaren, 25 mg t.i.d.) and indomethacin (25 mg t.i.d). Both drugs led to a clear-cut decrease in morning stiffness, as well as to a significant improvement in pain at rest and on movement. In these respects no significant difference between the two-drugs was observed. As regards their effect on status of rheumatoid condition, however, a trend towards a significant improvement was discernible, in the investigator's opinion, only in response to diclofenac sodium. "Unwanted effects" were mentioned by 25 patients before the trial, by 31 during treatment with diclofenac sodium, and by 33 during treatment with indomethacin. While the patients were receiving indomethacin, five of them discontinued treatment on account of side effects (headache in three cases, headache and tiredness in one case, and an allergic skin reaction in one case) and one of them, who complained of headache, lowered the dosage; treatment with diclofenac sodium was discontinued because of side effects by only one patient, who had developed an allergic skin reaction.
 ...
PMID:Diclofenac sodium (Voltaren) and indomethacin in the ambulatory treatment of rheumatoid arthritis: a double-blind multicentre study. 35 46

1. Latency relaxation and twitch tension were recorded simultaneously in single isolated muscle fibres of Xenopus laevis. 2. During low frequency (0.6 or 1 pulse/sec) repetitive stimulation, three successive phases of twitch tension were observed: negative staricase (a slight drop in tension), positive staircase (about 15% increase in tension) and fatigue. At the same time the amplitude of latency relaxation decreased monotonically, and near the peak of positive staircase, the amplitude decreased almost to an undetectable level. 3. The application of caffeine (0.1--1.5 mM) increased peak twitch tension by 15--200%, but decreased the latency relaxation amplitude by 30--93%. 4. The application of Ca-release inhibitors, deuterium oxide and dantrolene sodium, caused a 43--89% decline in peak twitch tension but no change in latency relaxation amplitude. 5. The lack of correlation between changes in peak twitch tension and latency relaxation amplitude suggests that latency relaxation is associated with the mechanism which triggers Ca2+ relase rather than with Ca2+ release itself.
 ...
PMID:Latency-relaxation in single muscle fibres. 72 20

In aerial combat maneuvers (ACMs), at Luke AFB, Az, eight pilots flew their two F-15 aircraft against nine pilots in three F-106 aircraft. A total of nine flights, consisting of 23 ACMs, were accomplished in 5 successive days. The degrees of fatigue, stress, and sympathetic activity were quantified using both subjective analyses and the biochemical constituents in the urine of the pilots of the F-15 or F-106. Biochemical indicators, reported per 100 mg creatinine, included: epinephrine, norepinephrine, 17-OHCS, urea, inorganic phosphate, sodium, potassium, and sodium/potassium ratio. The F-106 pilots exerted more relative effort than did the F-15 pilots--effort which appeared to be associated with high-G experience. Both groups of pilots were equally fatigued following ACMs; however, only the fatigue of the F-106 pilots was directly correlated with the length of the ACM. Sympathetic and stress responses during the ACM--similar for both groups of pilots--showed postflight increases of 54% in epinephrine, 19% in norepinephrine, and 20% in 17-OHCS over preflight values, thus suggesting a moderate stress response. Resting levels of these same indicators, for days the pilots did not fly and for pre-ACM values, were similar but higher than control values previously reported for other stressful activities. By late afternoon, postflight values for these indicators had returned to near-preflight levels.
 ...
PMID:Stress responses of pilots flying high-performance aircraft during aerial combat maneuvers. 87 Dec 90

Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered, although their serum CO2-combining power changed little. There was no correlation of the symptom complex with serum potassium concentration, except in a few patients who were simultaneously receiving chlorothiazide diuretics for systemic hypertension and who became frankly hypokalemic.
 ...
PMID:Carbonic anhydrase inhibitor side effects. Serum chemical analysis. 88 13


1 2 3 4 5 6 7 8 9 10 Next >>