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)

Similar movement disorders developed in two 8-year-old retarded children while they were receiving phenytoin. Seizures subsequent to a diphtheria-pertussis-tetanus immunization had developed in each child at 1 to 2 months of age. A static encephalopathy ensued, characterized by mental retardation, ataxia, spasticity, and a mixed seizure disorder. Intermittent dystonia and choreoathetosis developed insidiously while serum phenytoin concentrations were in the therapeutic range. Sustained dystonia and choreoatheosis developed 2 hours after an oral provocation with phenytoin. The baseline abnormalities on the electroencephalogram remained unchanged during the choreoathetosis. Recognizable metabolic abnormalities known to be associated with similar movement disorders were excluded. It was concluded from these studies that the movement disorder is secondary to phenytoin and can occur at therapeutic serum concentrations. Phenytoin is a central anticholinergic agent and a central stimulant of serotonin, and may induce movement disorders as a result of altering these neurotransmitters in the brain. The variable expression of these movement disorders may relate to the nature of the preexisting striatal insult.
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PMID:Phenytoin-induced dystonia and choreoathetosis in two retarded epileptic children. 94 1

Several different drugs are now used, or are potentially useful, to treat patients with spasticity. Although these compounds vary in their actions on spinal neurons and reflex arcs, it is possible to formulate reasonable hypotheses regarding their modes of action. The benzodiazepines bind to specific benzodiazepine receptors linked to classic gamma-aminobutyric acid (GABA) receptors located on the terminals of primary afferent fibers. This binding results in an increased affinity of the GABA receptor for the amino acid, an augmented flux of chloride ions across the terminal membrane, and an increase in the amount of presynaptic inhibition. Baclofen activates GABAB receptors putatively located on the same terminals. Activation of these receptors retards the influx of calcium ions into the terminals, thereby reducing the evoked release of excitatory amino acids and possibly other transmitters. Progabide and its metabolites act on both classic and GABAB receptors. Glycine works on specific inhibitory receptors located on spinal interneurons and motoneurons. The phenothiazines act on the brainstem to alter the function of fusimotor fibers. Phenytoin and carbamazepine reduce the afferent output of muscle spindles. Dantrolene diminishes the activation of the contractile process in muscle fibers by reducing the release of calcium ions from the sarcoplasmic reticulum. This review summarizes the data supporting these concepts.
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PMID:Antispasticity drugs: mechanisms of action. 285 76

The functional impairment due to spasticity must be carefully assessed before any treatment is considered. Therapeutic intervention is best individualized to a particular patient. Basic principles of treatment to ameliorate spastic hypertonia are: 1) avoid noxious stimuli and 2) provide frequent range of motion. Therapeutic exercise, cold or topical anesthesia may decrease reflex activity for short periods of time in order to facilitate minimal motor function. Casting and splinting techniques are extremely valuable to extend joint range diminished by hypertonicity. Baclofen, diazepam and dantrolene remain the three most commonly used pharmacologic agents in the treatment of spastic hypertonia. Baclofen is generally the drug of choice for spinal cord types of spasticity, while sodium dantrolene is the only agent which acts directly on muscle tissue. Phenytoin with chlorpromazine may be potentially useful if sedation does not limit their use. Tizanidine and ketazolam, not yet available in the United States, may be significant additions to the pharmacologic armamentarium. Intrathecal administration of antispastic medications allows high concentrations of drug near the site of action, which limits side effects. This form of treatment is the most exciting recent development in the treatment of spastic hypertonia. Peripheral electrical stimulation may have limited use in diminishing tone and facilitating paretic muscles. Dorsal column stimulation via electrodes within the spinal column was initially hailed as a therapeutic advance, but has subsequently been shown to be minimally effective. Phenol injections provide a valuable transition between short-term and long-term treatments and offer remediation of hypertonia in selected muscle groups. Tenotomies and tendon transfers offer significant benefit in carefully chosen patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of spasticity. 328 46

Phenytoin (DPH) was evaluated for its capacity to reduce several motor manifestations of decerebrate rigidity in the cat. In doses of the order of 40 to 50 mg/kg i.v., DPH diminished the force necessary to collapse the hyperextended limbs; at about half this dose range, the drug reduced gamma-motoneuron discharges; at still lower doses the drug profoundly depressed mechanical and electromyographic responses evoked by stretch from both forelimb and hindlimb extensor muscles. Serum levels of DPH associated with substantial reduction in electrical and mechanical manifestations of the extensor hypertonus were of the same order conventionally encountered when the drug is administered to humans for acute seizure management. The data are supportive of a centrally and peripherally mediated muscle relaxing effect of the drug in states where muscle spindle involvement is a contributing factor, and may help to explain further the utility of DPH in the treatment of spasticity.
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PMID:Description and analysis of the myotonolytic effects of phenytoin in the decerebrate cat: implications for potential utility of phenytoin in spastic disorders. 396 98