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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent in vitro and in vivo experiments have suggested that excitatory amino acid antagonists, particularly those active at the N-methyl-D-aspartate receptor subtype, are effective in ameliorating ischemic injury due to their antiexcitotoxic activity. However, these drugs are also potent and effective in vivo anticonvulsants. The present experiments compared the noncompetitive N-methyl-D-aspartate antagonists phencyclidine and MK-801 with the anticonvulsant phenytoin in a model of focal brain ischemia. Fisher F-344 rats were subjected to tandem occlusion of the middle cerebral and ipsilateral common carotid arteries under halothane anesthesia. Compounds were administered intravenously 30 minutes and 24 hours after arterial occlusion; infarct size was assessed at 48 hours after occlusion. Phencyclidine had no effect on infarct volume at 1 mg/kg, significantly reduced (by 36%) infarct volume at 3 mg/kg, and produced a nonsignificant 26% decrease at 10 mg/kg. The more potent and selective noncompetitive antagonist MK-801 reduced (by 32%) infarct volume significantly at 0.1 mg/kg, produced a nonsignificant 23% decrease at 0.3 mg/kg, and had no effect at 0.5 mg/kg. Phenytoin, which is not a glutamate antagonist, reduced the infarct volume by 45% at 28 mg/kg. A single dose of phenytoin (28 mg/kg) administered 30 minutes after occlusion was neuroprotective, but delaying drug administration for more than 2 hours was ineffective. These data suggest that blockade of the N-methyl-D-aspartate receptor is effective in reducing the infarct size after focal cerebral ischemia. The neuroprotective activity of phenytoin suggests that this may be related to the common anticonvulsant action.
Stroke 1990 Nov
PMID:Comparison of phenytoin with noncompetitive N-methyl-D-aspartate antagonists in a model of focal brain ischemia in rat. 223 85

We investigated the effects of phenytoin on the rate of enzymatic release of free fatty acids and on the levels of energy metabolites and nucleoside phosphates in ischemic brain. Phenytoin (10 mg/kg i.v.) was administered 30 minutes before the onset of ischemia induced in 30 male Wistar rats by occluding the basilar and both common carotid arteries. The rats' brains were frozen in situ after 0, 5, or 30 minutes of ischemia or 10, 30, or 60 minutes of recirculation following 30 minutes of ischemia (n = 5 at each time). Nucleoside triphosphate levels were higher in the phenytoin-treated rats than in corresponding untreated rats at each time during and after ischemia. Phenytoin significantly attenuated the accumulation of lactate and free fatty acids (arachidonic acid and stearic acid) during ischemia and accelerated their recovery during recirculation. These results suggest that phenytoin has favorable protective effects on ischemic brain and that phenytoin may inhibit calcium-mediated phenomena, especially the inositol cycle, in cerebral ischemia.
Stroke 1990 Sep
PMID:Phenytoin affects metabolism of free fatty acids and nucleotides in rat cerebral ischemia. 239 70

We looked at FiO2, choice of anesthetic, nutritional status, and body temperature in a gerbil model of forebrain ischemia to determine their effect on data interpretation, ischemic outcome, and extent of pharmacologic protection. We subjected 484 gerbils to 5 minutes of forebrain ischemia under different experimental conditions. The gerbils were anesthetized with 3% halothane and inspired 21% O2, 37% O2 and 60% N2O, or 97% O2. Six groups of gerbils pretreated with 200 mg/kg phenytoin or 2 ml/kg polyethylene glycol (vehicle) underwent ischemia in the fasted or fed state. Three groups of gerbils receiving no pretreatment underwent ischemia with rectal temperatures of 32-33 degrees C, 34-35 degrees C, or 37 degrees C. We counted intact neurons in the CA1 hippocampal sector in brains fixed on Day 7 after ischemia. t tests of square-root-transformed cell counts were used to assess the effect of hypothermia, and analysis of variance of the transformed data was used to test for the effects of phenytoin, FiO2, and nutritional status. Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%. In spite of significantly higher serum glucose concentrations in fed than in fasted gerbils (173 and 118 mg/dl, respectively), we found no significant effect of nutritional status upon neuron loss in phenytoin- or vehicle-pretreated gerbils. An FiO2 of 21% significantly decreased the number of viable neurons in both vehicle- and phenytoin-pretreated groups (p less than 0.03), despite the lack of an effect of hypoxemia on arterial blood gases.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1989 Nov
PMID:Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia. 281 90

Medical records for 572 patients in two extended care facilities were reviewed to study seizure disorders and antiepileptic drug use. Seventy patients (12.2 percent) were receiving antiepileptic drugs. Of this group, 43 patients (61.4 percent) had a diagnosis of epilepsy or documented seizures, 2 were being treated for neuralgia, and 25 (35.7 percent) had no reason given for antiepileptic use. The most common cause was cerebrovascular accident (38.9 percent), and no associated etiology was found in 29.2 percent. Phenytoin was the most commonly used agent. Thirty-two (45.7 percent) were taking two or more antiepileptic drugs. Thirteen patients had had no serum concentration monitoring in the last year. Thirty-seven patients (52.9 percent) had had at least one serum concentration outside of the therapeutic range.
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PMID:Use of antiepileptic drugs in the elderly population. 310 51

Phenytoin has a wide range of pharmacologic effects other than its anticonvulsant activity. It has been the subject of more than 8,000 published papers, which include clinical reports of its usefulness in approximately 100 diseases and symptoms. In the United States the only indications for use in the official labeling for phenytoin are various types of seizures. An advisory committee of the Food and Drug Administration recently recommended the addition of certain cardiac arrhythmias to the labeling. To determine whether other uses should be added to the labeling and whether additional clinical trials should be encouraged, an in-depth review of the published literature was undertaken. This review revealed that, on the basis of controlled studies, phenytoin is probably useful in the continuous muscle fiber activity syndrome, myotonic muscular dystrophy, and myotonia congenita. In addition, phenytoin appears to be potentially useful in recessive dystrophic epidermolysis bullosa, intermittent explosive disorder, anxiety disorder in which anger and irritability are prominent features, and, topically, in burns and refractory skin ulcers. Additional clinical studies are needed before definitive conclusions can be drawn. Clinical trials of phenytoin in most of these disorders are ongoing or are contemplated. Any labeling changes will await results of the studies. Based on phenytoin's pharmacologic effects in animals, controlled trials of the drug appear to be warranted in cerebral ischemia and stroke, spinal cord injury, angina pectoris, and fractures in which the rate of healing is poor.
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PMID:Phenytoin revisited. 638 10

Serum high density lipoprotein (HDL) cholesterol and other lipoproteins were measured in 27 TIA-patients with a mean age of 49 +/- 10 years before and during phenytoin therapy. The pretreatment concentrations of HDL-cholesterol (mmol/l, mean +/- SD) were lower (p less than 0.001) in male (1.03 +/- 0.25) and in female patients (1.15 +/- 0.44) than in healthy male (1.28 +/- 0.34) and female controls (1.52 +/- 0.31) respectively. After one month's phenytoin therapy HDL cholesterol concentrations reached normal levels (men 1.33 +/- 0.38, women 1.61 +/- 0.27) and after 9 months of therapy even surpassed them (men 1.47 +/- 0.27, p less than 0.05; women 1.91 +/- 0.33, p less than 0.01). Percent increase of HDL cholesterol after 9 months of therapy was 42 +/- 25 in men and 68 +/- 46 in women. There was a positive correlation (r = 0.43, p less than 0.05) between serum phenytoin level and increase of HDL cholesterol. HDL/LDL cholesterol ratio increased (p less than 0.01) also during 9 months of therapy (men from 0.26 +/- 0.05 to 0.36 +/- 0.10, women from 0.26 +/- 0.07 to 0.43 +/- 0.13) and showed a positive correlation (r = 0.91, p less than 0.001) with increase of serum HDL cholesterol. The HDL cholesterol levels achieved have been maintained with a mean serum phenytoin level of 5.6 +/- 3.6 mg/l. Phenytoin induced increase in serum HDL levels should not yet be equated with protection against atherosclerosis.
Stroke
PMID:Increase of low serum concentrations of high-density lipoprotein (HDL) cholesterol in TIA-patients treated with phenytoin. 665 26

The hippocampal formation, which contains high levels of adrenal steroid receptors, is vulnerable to insults such as stroke, seizures, and head trauma, and it is also sensitive and vulnerable to the effects of stress. We have discovered that the hippocampus of rodents and tree shrews shows atrophy of pyramidal neurons in the CA3 region. Psychosocial stress and restraint stress produce atrophy over approximately 3-4 weeks. Atrophy is blocked by inhibiting adrenal steroid formation and by blocking the actions of excitatory amino acids using Dilantin or NMDA receptor inhibitors. Glucocorticoid administration also blocks CA3 atrophy, but Dilantin administration blocks this as well, indicating that excitatory amino acid release mediates the atrophy, which likely involves disassembly of the dendritic cytoskeleton. Studies with in vivo microdialysis in several laboratories have shown that glutamate release in the hippocampus increases in stress and that stress-induced glutamate release is reduced by adrenalectomy. Recent electron microscopy of mossy fiber terminals on CA3 neurons has revealed a depletion of synaptic vesicles as a result of repeated stress. The mossy fiber terminals appear to be responsible for driving atrophy of CA3 neurons, which involves principally atrophy of the apical dendrites. These results are discussed in relation to data from MRI showing atrophy of the whole human hippocampus in Cushing's disease, recurrent depressive illness, PTSD, and normal aging as well as dementia.
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PMID:Stress effects on morphology and function of the hippocampus. 923 11

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from 11 min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CA1 pyramidal neurons. Topiramate, when administered i.v. 30 min after resuscitation, reduced the degree of motor impairment (P< 0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P< 0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg i.v.) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P< 0.001). Phenytoin at 20 mg/kg i.v. exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg i.v.. In normal rats, neither topiramate nor phenytoin at 20 mg/kg i.v. induced any apparent neurological impairment; however, at 40 and 60 mg/kg i.v. both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties.
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PMID:Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration. 1166 69

Phenytoin is a commonly prescribed antiepileptic drug. Due to its saturation (zero-order) pharmacokinetics, phenytoin carries a special risk of dose-related toxicity that is an important issue in emergency medicine. The purpose of this cross-sectional case-series study was to investigate the causes, symptoms, misdiagnoses, and outcomes of acute phenytoin intoxication. It was based on a retrospective chart review of 30 inpatients (mean age, 41.6 +/- 22.8 years) with 36 episodes of acute phenytoin intoxication at our university hospital in the past 13 years. The average initial serum phenytoin level was 47.3 +/- 9.7 microg/mL (range, 27.9-70.4 microg/mL). Excessive self-medication, misunderstanding of the prescription order, and probable drug interaction were the three leading causes of acute phenytoin intoxication. Unsteady gait, dizziness/vertigo, nausea/vomiting, general weakness, and drowsiness were the most common presenting symptoms. The tentative diagnostic accuracy was 67%. The most common initial misdiagnosis was brainstem or cerebellum stroke (14%). The clinical course in all patients was uneventful under temporary withdrawal of phenytoin and supportive care. We concluded that acute phenytoin intoxication was relatively under-diagnosed in the emergency service. Although acute phenytoin intoxication causes no mortality and has a good outcome, the unsteady gait increases the risk of injuries caused by falls. The management of acute phenytoin intoxication includes temporary withdrawal of phenytoin and supportive care.
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PMID:Acute phenytoin intoxication: causes, symptoms, misdiagnoses, and outcomes. 1569 87

The life-threatening DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is characterized by the presence of at least three of the following findings: fever, exanthema, eosinophilia, atypical circulating lymphocytes, lymphadenopathy, and hepatitis. This syndrome is difficult to diagnose, as many of its clinical features mimic those found with other serious systemic disorders. This idiosyncratic reaction occurs most commonly after exposure to drugs such as allopurinol, sulfonamides, and aromatic anticonvulsants such as phenytoin, phenobarbital, and carbamazepine. We describe a 44-year-old woman who was brought to the emergency department with new-onset hemorrhagic stroke. She was admitted to the intensive care unit where she received supportive care that included clonidine and hydralazine for blood pressure control and phenytoin for seizure prophylaxis. On hospital day 21, the patient developed signs and symptoms of severe sepsis. Despite receipt of broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam) and supportive care, the patient's clinical condition worsened with progressive jaundice, severe oliguria, and labile blood pressures. All cultures revealed no growth, and her chest radiograph remained clear. Several days after the onset of her fever, the patient developed several hematologic abnormalities including thrombocytopenia, with schistocytes present on a peripheral smear. She also had an elevated lactate dehydrogenase level. A provisional diagnosis of thrombotic thrombocytopenic purpura was made; however, the patient then developed severe facial edema, nearly global erythroderma, and severe exfoliative dermatitis. A punch biopsy of the skin was compatible with the DRESS syndrome. Phenytoin, vancomycin, and piperacillin-tazobactam were discontinued, and the patient was started on systemic corticosteroids, with rapid resolution of her fever and eosinophilia and progressive improvement in her skin rash and multiorgan system dysfunction. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of DRESS syndrome and treatment with phenytoin. Clinicians should have a high index of suspicion for the DRESS syndrome in patients being treated with aromatic anticonvulsants who develop a sepsis-like syndrome. Furthermore, considering the potential severe effects associated with phenytoin, the risks and benefits should be carefully evaluated before using this agent for seizure prophylaxis.
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PMID:The DRESS syndrome: the great clinical mimicker. 2136 42


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