Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with dystrophia myotonica was given dantrolene sodium to try to provide muscle relaxation during a cholecystectomy. Dantrolene was used as it is accepted that the drug has a place in the control of spasticity and also causes muscle relaxation, whereas conventional muscle relaxants are unable to control myotonia of muscle origin. Dantrolene alone did not provide good enough intubating and operating conditions in this subject. Later studies showed that, after dantrolene, EMG recordings from the patient were not significantly altered, although an impression of a slight increase in the myotonic potentials was gained.
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PMID:Dantrolene sodium and dystrophia myotonica. 674 90

Malignant hyperthermia (MH) is a genetic, potentially life-threatening disorder of the skeletal muscle presenting during or following general anaesthesia. Trigger agents are volatile anaesthetics and depolarising muscle relaxants. Dantrolene is the only available drug for effective and specific MH therapy, which reduces significantly the mortality rate. Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown. Recent studies identified the ryanodine receptor, the calcium release channel of the sarcoplasmic reticulum, as the direct molecular target of dantrolene. In addition to its use for MH, dantrolene is used in other disorders such as neuroleptic malignant syndrome and spasticity. Since dantrolene is weakly water soluble, the clinical preparation is time and manpower consuming. New agents have been synthesized, but because of economic considerations no registration for clinical usage has been realised.
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PMID:[Dantrolene. Pharmacological and therapeutic aspects]. 1266 6

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.
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PMID:Dantrolene--a review of its pharmacology, therapeutic use and new developments. 1547 27

Skeletal muscle relaxants are a heterogeneous group of medications used to treat two different types of underlying conditions: spasticity from upper motor neuron syndromes and muscular pain or spasms from peripheral musculoskeletal conditions. Although widely used for these indications, there appear to be gaps in our understanding of the comparative efficacy and safety of different skeletal muscle relaxants. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included oral medications classified as skeletal muscle relaxants by the FDA were sought using electronic databases, reference lists, and pharmaceutical company submissions. Searches were performed through January 2003. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 101 randomized trials were included in this review. No randomized trial was rated good quality, and there was little evidence of rigorous adverse event assessment in included trials or observational studies. There is fair evidence that baclofen, tizanidine, and dantrolene are effective compared to placebo in patients with spasticity (primarily multiple sclerosis). There is fair evidence that baclofen and tizanidine are roughly equivalent for efficacy in patients with spasticity, but insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine. There is fair evidence that although the overall rate of adverse effects between tizanidine and baclofen is similar, tizanidine is associated with more dry mouth and baclofen with more weakness. There is fair evidence that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions (primarily acute back or neck pain). Cyclobenzaprine has been evaluated in the most clinical trials and has consistently been found to be effective. There is very limited or inconsistent data regarding the effectiveness of metaxalone, methocarbamol, chlorzoxazone, baclofen, or dantrolene compared to placebo in patients with musculoskeletal conditions. There is insufficient evidence to determine the relative efficacy or safety of cyclobenzaprine, carisoprodol, orphenadrine, tizanidine, metaxalone, methocarbamol, and chlorzoxazone. Dantrolene, and to a lesser degree chlorzoxazone, have been associated with rare serious hepatotoxicity.
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PMID:Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. 1527 95

A fever of unknown origin developed in a patient with sequelae of acute encephalopathy who had received dantrolene for severe spasticity. A chronic subdural hematoma was found on MRI, and initially it was suspected that the patient had an intracranial infection. However, close investigation ruled out the chronic subdural hematoma as the source of infection. The patient's fever continued in spite of administration of antibiotics and antimycotics. We suspected that the fever was drug-induced and discontinued the use of dantrolene. As a result, the patient's fever promptly went down. After discontinuation of dantrolene the patient experienced increased muscle tone, vomiting and sleep disturbances. Dantrolene was readministered with the consent of the patient's family, but the fever returned. When dantrolene was once again discontinued, the fever immediately went down. We concluded that the fever of the patient was induced by dantrolene.
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PMID:[Recurrent fever related to dantrolene sodium in a girl with sequelae of acute encephalopathy]. 1802 66

Dantrolene is the drug of choice for the treatment of malignant hyperthermia (MH) and is also useful for treatment of spasticity or muscle spasms associated with several clinical conditions. The current study examines the mechanisms of dantrolene's action on skeletal muscle and shows that one of dantrolene's mechanisms of action is to block excitation-coupled calcium entry (ECCE) in both adult mouse flexor digitorum brevis fibers and primary myotubes. A second important new finding is that myotubes isolated from mice heterozygous and homozygous for the ryanodine receptor type 1 R163C MH susceptibility mutation show significantly enhanced ECCE rates that could be restored to those measured in wild-type cells after exposure to clinical concentrations of dantrolene. We propose that this gain of ECCE function is an important etiological component of MH susceptibility and possibly contributes to the fulminant MH episode. The inhibitory potency of dantrolene on ECCE found in wild-type and MH-susceptible muscle is consistent with the drug's clinical potency for reversing the MH syndrome and is incomplete as predicted by its efficacy as a muscle relaxant.
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PMID:Enhanced excitation-coupled calcium entry in myotubes expressing malignant hyperthermia mutation R163C is attenuated by dantrolene. 1817 28

We report a case of a 49-year-old female with cerebral palsy with spastic tri-plegia and lumbar spondyolisthesis diagnosed to have overactive neurogenic bladder, which improved on treatment with Dantrolene along with antimuscarinics. She was initially treated with antimuscarinics both transdermal and oral simultaneously and later received intravesical OnaBotulinum toxinA. Following lumbar spine fixation for spondylolisthesis, her bowel and bladder function deteriorated and she was commenced on Dantrolene for her spasticity, along with being on Oxybutinin and Mirabegron. This significantly improved her symptoms. Overactive bladder symptoms are a common manifestation in cases of CP. In refractory cases where antimuscarinics and intravesical botulinum toxin therapy have failed, a combination of Dantrolene with antimuscarinics and/or beta 3 receptor agonists may prove to be beneficial. While on therapy, regular monitoring of liver functions is required to promptly diagnose and treat hepatotoxicity.
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PMID:Dantrolene an unusual option for detrusor overactivity: observations of a patient with cerebral palsy. 2636 33

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal complication resulting from neuroleptic drug therapy. Presentation of NMS can vary, and diagnosis relies primarily upon medical history and symptomatology. Due to the potential delay in diagnosis, emergency physicians should remain vigilant in recognizing the symptoms of NMS and be prepared to initiate immediate treatment following diagnosis. Dantrolene, which has been used for spasticity and malignant hyperthermia, has been reported as a potential treatment for NMS and led to off-label use for NMS. We report two cases of NMS induced by antipsychotic monotherapy for which dantrolene was administered.
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PMID:Emergent Treatment of Neuroleptic Malignant Syndrome Induced by Antipsychotic Monotherapy Using Dantrolene. 3077 57

Dantrolene capsule, an effective therapeutic agent for the treatment of spasticity, is administered to children who cannot swallow the capsule after reformulation into a powder. The powdered drug can alter the specified dosage and it is also difficult to dispense the powdered formulation because of its bulky and sticky nature. To resolve these problems, we reformulated dantrolene capsules into granules using a centrifugal planetary mixer in the pharmacy. The granules containing lactose-cornstarch, D-mannitol, or microcrystalline cellulose as a diluent were examined to determine particle size distribution, flowability, drug content uniformity, and disintegration time. The granules with microcrystalline cellulose were superior to the other forms, owing to their smaller size, good drug content uniformity, and rapid disintegration. We further investigated the usability of the granules in the dispensing procedure (dividing and packing) and in the dosing process (retrieval from package) using the powders as controls. The deviation of the divided amount and loss on dosing were reduced relative to the powders. In addition, drug dissolution properties and storage stability for 12 months were the same as those of the powders. Therefore, we concluded that dantrolene granules are excellent alternatives as an extemporaneous preparation in pharmacies.
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PMID:Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy. 3299 51


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