Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 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

Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.
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PMID:Plasma levels of dantrolene following oral administration in malignant hyperthermia-susceptible patients. 305 38