Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To provide information regarding the cause of the muscle rigidity in malignant hyperthermia-susceptible (MHS) pigs, the Ca-induced Ca-release mechanism of the sarcoplasmic reticulum (SR), the Ca uptake by the SR, and the Ca-activated tension production of the contractile system were examined in skinned skeletal muscle fibers from MHS and normal pigs. In muscles of MHS pigs, the rate of Ca-induced Ca release was significantly higher than in normal muscle. The potentiation effect on Ca-induced Ca release by halothane and caffeine did not differ appreciably between MHS and normal fibers. The rate of Ca uptake by the SR and the Ca sensitivity of the contractile system of MHS fibers were not different from those of normal fibers, and halothane in an anesthetic concentration exerted no effect on them. Dantrolene inhibited the Ca-induced Ca release at 38 degrees C. These results suggest that the principal cause of malignant hyperthermia (MH) in MHS pigs is due to the enhancement of the Ca-induced Ca-release mechanism of the SR of the skeletal muscle.
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PMID:Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle. 291 63

The use of dantrolene to reverse severe unexplained postanaesthetic muscle rigidity in a previously "healthy" 13-year-old male is described. Anaesthesia was induced with thiopentone. After intubation with pancuronium, the patient had an entirely uneventful nitrous oxide, oxygen and halothane anaesthetic. Immediately following reversal of the relaxant, the patient developed generalized muscle tightness and rigidity involving the trunk and extremities. This was prolonged and severe enough to interfere with adequate ventilation. The patient also had a prolonged recovery from the anaesthetic. After ruling out malignant hyperthermia and some other causes of rigidity, a tentative diagnosis of myotonia was made. The symptoms responded to IV dantrolene in a total dose of 2.0 mg.kg-1. Further testing failed to establish a definite diagnosis. Dantrolene could be a useful drug in treating such unexplained muscle rigidity.
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PMID:Reversal of prolonged postoperative muscle rigidity by dantrolene: a case report. 340 20

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.
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PMID:Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. 352 59

Malignant hyperthermia (MHS) is a rare potentially fatal complication of general anesthesia. Anesthetic agents most frequently incriminated are succinylcholine and halogenated agents. Respiratory acidosis is the most specific and sensitive sign. Hyperthermia per se may occur secondarily or may stay totally absent. Tachycardia and/or arrhythmias often develop due to hyperkalemia and metabolic acidosis. Muscle rigidity whenever present is pathognomonic The "gold standard" test for the diagnosis of MHS is the halothane-caffeine contracture test. Dantrolene is the treatment of choice and prognosis depends on the early administration of this agent.
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PMID:[Intraoperative malignant hyperthermia: apropos of a case]. 945 94

Malignant hyperthermia (MH) is a hypermetabolic syndrome triggered in genetically susceptible individuals when certain potent inhalation anesthetics or succinylcholine are administered. The signs of MH include a greatly increased body metabolism, muscle rigidity and eventual hyperthermia that may exceed 110 degrees F. Death can result from cardiac arrest, brain damage, internal hemorrhaging or failure of other body systems. Dantrolene is given until the manifestations of MH abate. The initial dose is 2.5 mg/kg body weight; and repeated as needed. High-risk patients cannot always be identified by history, and preparation of every OR is essential. Supplies of dantrolene and other medications must be kept in the OR area. If MH develops, acting within minutes may save a life.
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PMID:Malignant hyperthermia: an OR emergency! 1202 57

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction to neuroleptic drugs, which is potentially fatal. It has been occasionally reported that NMS occurs subsequently after surgery. We report a case of a 53-year-old male patient who developed NMS following cardiac surgery due to the resumption of zotepine. The patient was attacked with hyperthermia, sweating, significant shivering, trembling of the fingers, disturbed consciousness and extreme muscle rigidity after the resumption of zotepine. Furthermore, laboratory measurements revealed increased levels of serum blood urea nitrogen, creatinine and creatine phosphokinase. In addition, elevation in white blood cell counts and myoglobinemia were also observed. After a diagnosis of NMS was established, administration of zotepine was stopped and treatments with administration of dantrolene and a large amount of fluid infusion intravenously were started. Following these treatments, the clinical symptoms subsided and the laboratory findings improved without need for hemodialysis. Dantrolene, which is able to effectively impede the abnormal flow of calcium from the sarcplasmic reticulum into the muscle cytoplasm, was beneficial to reduce the clinical symptoms of NMS. We hereby present a patient with NMS following cardiac surgery, and discuss its subsequent management.
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PMID:Neuroleptic malignant syndrome following cardiac surgery: successful treatment with dantrolene. 1296 23

A 64-year-old man without any psychiatric disease, including Parkinson's disease underwent aortic valve replacement and mitral valve replacement for rheumatic valvular disease. One day after the cardiac surgery, he developed hyperthermina, muscle rigidity, coma and delirium, and his serum creatine kinase (CK) level was elevated. In spite of his negative brain computed tomography(CT), his consciousness remained unclear. He had received diazepam, flunitrazepam and buprenorphine after the cardiac surgery because of his hyper-reactivity. Although these drugs were not typical antipsychotics' causing neuroleptic malignant syndrome (NMS), NMS was strongly suspected because of his clinical appearance. Dantrolene was administered in a dose of 60 mg per day and he recovered consciousness and his CK level began to decrease. We reported a case of neuroleptic malignant syndrome after cardiac surgery.
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PMID:[Neuroleptic malignant syndrome after cardiac surgery]. 2432 11

Dantrolene-a nitrofurantoin derivative-was developed by Snyder et al. in 1967. After initial discovery of its muscle relaxation potential, investigations in a number of species demonstrated dose-dependent reductions in skeletal muscle tone that were long lasting, relatively nontoxic, and free of adverse effects such as respiratory impairment. Ellis et al. then published a number of papers investigating the means by which dantrolene produced these effects. Using a series of classic physiologic models, Ellis investigated potential sites of action for the new drug, eventually narrowing this down to the intracellular calcium-release mechanism. Ellis went on to play a pivotal role in the discovery of dantrolene's effectiveness for the treatment of malignant hyperthermia, after reading a scientific bulletin about muscle rigidity in pigs affected by porcine stress syndrome, contacting Gaisford Harrison and sending dantrolene to him for trial.
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PMID:Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D. 2827 43

Malignant hyperthermia (MH) is a rare and life-threatening pharmacogenetic disorder triggered by volatile anesthetics, the depolarizing muscle relaxant succinylcholine, and rarely by strenuous exercise or environmental heat. The exact prevalence of MH is unknown, and it varies from 1:16 000 in Denmark to 1:100 000 in New York State. The underlying mechanism of MH is excessive calcium release from the sarcoplasmic reticulum (SR), leading to uncontrolled skeletal muscle hyper-metabolism. Genetic mutations in ryanodine receptor type 1 ( RYR1) and CACNA1S have been identified in approximately 50% to 86% and 1% of MH-susceptible (MHS) individuals, respectively. Classic clinical symptoms of MH include hypercarbia, sinus tachycardia, masseter spasm, hyperthermia, acidosis, muscle rigidity, hyperkalemia, myoglobinuria, and etc. There are two types of testing for MH: a genetic test and a contracture test. Contracture testing is still being considered as the gold standard for MH diagnosis. Dantrolene is the only available drug approved for the treatment of MH through suppressing the calcium release from SR. Since clinical symptoms of MH are highly variable, it can be difficult to establish a diagnosis of MH. Nevertheless, prompt diagnosis and treatments are crucial to avoid a fatal outcome. Therefore, it is very important for anesthesiologists to raise awareness and understand the characteristics of MH. This review summarizes epidemiology, clinical symptoms, diagnosis and treatments of MH and any new developments.
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PMID:The current status of malignant hyperthermia. 3230 61