Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Rhabdomyolysis, a term used to describe the rapid breakdown of striated muscle, is characterized by rupture and necrosis of muscle fibers. This process results in the release of cell breakdown products into the bloodstream and extracellular space. Although direct muscle injury remains the most common cause of muscle injury, additional causes include hereditary enzyme disorders, drugs, toxins, endocrinopathies, malignant hyperthermia, neuroleptic malignant syndrome, heatstroke, hypothermia, electrolyte alterations, diabetic ketoacidosis and non-ketotic hyperosmolar coma, severe hypo- or hyperthyroidism and bacterial or viral infections. The classic triad of symptoms includes muscle pain, weakness and dark urine, although more than 50% of the patients do not complain of muscle pain or weakness. Additional systemic symptoms include fever, general malaise, tachycardia, nausea and vomiting. The laboratory diagnosis is based essentially on the measurement of creatine kinase in serum or plasma. Plasma and urine myoglobin measurement might be useful in the early stages of the syndrome and for identifying a subset of patients with minor skeletal muscle injury. Patient monitoring is pivotal (the mortality rate is as high as 8%), and should be focused on preventing the detrimental consequences, that often include renal disease and coagulopathy. In the pre-hospital setting, forced hydration with 1.5-2 L of sterile saline solution should be started immediately, followed by 1.5-2 L/h. Following hospital admission, continuous hydration should be ensured, alternating the saline solution with a 5% glucose solution. In the presence of myoglobinuria, urine should be alkalinized by use of sodium bicarbonate solution. Clin Chem Lab Med 2010;48:749-56.
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PMID:Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features. 2044 60