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)

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.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Clinical, electrophysiological and histological findings in four patients accidentally poisoned with the organophosphorus insecticide Dipterex are reported. Three to five weeks after insecticide ingestion signs of a distal sensorimotor (preponderantly motor) neuropathy occurred. The patients complained of paraesthesia in the lower limbs, and two of them of very disagreeable pricking sensation in the soles of the feet, responsive to carbamazepine. They showed distal weakness mainly of the legs, footdrop , difficult gait and muscle hypotonia. Ankle jerk was abolished while other tendon reflexes persisted. Two months or even later after poisoning, knee jerks in all the patients were very brisk and more and less accompanied by other pyramidal signs (patellar clonus, abolishment of abdominal cutaneous reflexes, Babinski's sign). Clinical, electrophysiological and nerve biopsy data revealed a "dying-back" neuropathy in our patients. Distal muscle fatigue was confirmed by failure of neuromuscular transmission on repetitive nerve stimulation.
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PMID:Delayed neuropathy after organophosphorus insecticide (Dipterex) poisoning: a clinical, electrophysiological and nerve biopsy study. 673 86

A double-blind trial with two parallel groups was carried out to compare the antispastic effect and tolerability of a new muscle relaxant, tizanidine (DS 103-282), with those of baclofen in the treatment of spasticity due to multiple sclerosis. Twenty-one hospitalized patients with stable spasticity participated in the 6-week trial. Eleven received tizanidine and 10 baclofen in gradually increasing daily doses. The optimal daily dose of tizanidine was between 8 and 36 mg and that of baclofen between 10 and 80 mg. Overall spastic state, spasms and clonus were similarly improved with both medications. In contrast, muscle strength, bladder function and the activities of daily living were more improved on tizanidine than on baclofen. Tiredness was the most frequent side-effect on tizanidine and muscle weakness on baclofen. The laboratory tests did not show any pathological changes with either medication. According to these results, tizanidine provides a new therapeutic alternative in the treatment of spasticity.
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PMID:A double-blind comparative trial of new muscle relaxant, tizanidine (DS 103-282), and baclofen in the treatment of chronic spasticity in multiple sclerosis. 701 49

The applicability of the auditory fatigue and anoxia hypotheses for the refractory period observed after sound-induced seizure was examined in SJL/J mice. Duration of auditory stimulation was varied independent of attainment of clonic seizure activity by use of an acoustic interruption technique. Duration of the recovery period affected the pattern of preconvulsive running. Furthermore, the motor asymmetries exhibited during clonus remained consistent across tests. Because duration of acoustic stimulation and attainment of clonus did not affect recovery rate, we conclude that neither the auditory fatigue nor the anoxia hypothesis provides a complete account for the refractory period after audiogenic seizure. We suggest that an inhibitory process, activated before clonus occurs and perhaps linked to depletion of excitatory amino acids in the inferior colliculus, may also be involved.
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PMID:Recovery of susceptibility to audiogenic seizure in mice. 842 56