Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.
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PMID:Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. 921 Oct 88

Topiramate is a new antiepileptic drug which has recently become available in the United States and in a number of European countries. Pharmacological studies suggest that its mode of action is multifactorial and involves blockade of voltage-dependent sodium channels, potentiation of GABAergic transmission and inhibition of excitatory pathways through an action at AMPA receptor sites. Carbonic anhydrase inhibiting properties have also been demonstrated but they are considered not to be relevant to anticonvulsant activity. Topiramate is well absorbed from the gastrointestinal tract, peak plasma levels being usually attained in 2-3 hours. The drug is negligibly (9-17%) bound to plasma proteins and is eliminated partly by renal excretion in unchanged form and partly by oxidation and hydrolysis. In healthy volunteers, the half-life is about 20-30 hours, but elimination rate is accelerated in patients taking concomitant enzyme inducing drugs such as phenytoin, carbamazepine and barbiturates. Topiramate has no major effects on plasma levels of concurrent anticonvulsants, except for a rise in plasma phenytoin in occasional patients. In double-blind add-on trials in refractory partial epilepsy, a significant reduction in seizure frequency has been demonstrated in over 40% of topiramate-treated patients (vs about 10% of those treated with placebo), a response rate which compares favourably with that observed with other new antiepileptic drugs. Dosages found to be effective in add-on controlled trials range between 200 and 1000 mg day-1, although most patients are likely to benefit from receiving 400 mg day-1 or less. Preliminary data suggest that topiramate may be effective also in generalized epilepsies, but this needs to be confirmed in prospective studies. The most common adverse effects of topiramate are CNS-related and include dizziness, fatigue, visual disturbances, ataxia, mental slowing and impaired concentration. Paresthesias, anorexia, weight loss and increased risk of nephrolithiasis have been also reported. Many of these effects are related to dose and/or to rate of dose titration. Based on these data, topiramate appears to be a valuable new drug, whose main current indication is in the add-on management of refractory partial and secondarily generalized seizures. Studies on its potential-value as monotherapy are in progress.
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PMID:A pharmacological and clinical review on topiramate, a new antiepileptic drug. 926 38

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is an antiepileptic drug recently approved by the United States Food and Drug Administration. It has a novel mechanism of action whereby it may decrease excitation by inhibiting glycine binding at the NMDA receptor, and it appears to have neuroprotective properties in addition to antiepileptic ones. A number of animal models have demonstrated felbamate to have a broad range of efficacy as well as a favorable safety profile. In humans it has been potentially linked to some cases of aplastic anemia. It is effective in the treatment of partial and secondarily generalized tonic-clonic seizures as well as seizures associated with the Lennox-Gastaut syndrome, especially drop attacks. It may also be effective against atypical absence as well as other seizure types. Felbamate monotherapy is generally well tolerated, with such side effects as insomnia and anorexia occurring most commonly. Felbamate shows great promise as a useful antiepileptic drug, but its role in clinical practice awaits further investigation of recently reported cases of aplastic anemia.
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PMID:Felbamate pharmacology and use in epilepsy. 931 88

This report describes vaccine-induced canine distemper virus (CDV) infection in four European mink (Mustela lutreola) induced by the administration of a multivalent, avian-origin vaccine. Clinical signs consisting of seizures, ataxia, facial twitching, oculonasal discharge, hyperkeratosis of footpads, and anorexia developed 16-20 days postvaccination. Conjunctival smears from one animal were positive for CDV antigen by direct fluorescent antibody testing, confirming the clinical diagnosis. The four mink died 16-26 days postvaccination. Gross and microscopic lesions that were diagnostic for CDV infection included interstitial pneumonia, lymphoid depletion, nonsuppurative encephalitis, and dermatitis. Vaccine-strain virus was isolated from tissues of three animals. Cases of vaccine-induced distemper in mustelids using avian-origin vaccine have seldom been reported.
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PMID:Vaccine-induced canine distemper in European mink, Mustela lutreola. 936 45

Six patients with severe and complicated falciparum malaria (6.7 +/- 2.7 WHO criteria) were admitted to our Intensive Care Unit. All patients acquired the disease while travelling in tropical Africa without appropriate chemoprophylaxis. The clinical manifestations included hyperpyrexia (all patients), chills (4), sweating (2), asthenia (3), anorexia (2), headache (1), arthralgias (1), vomiting (4), diarrhoea or abdominal discomfort (3), jaundice (2) and disturbances of consciousness (4). All patients had anemia, thrombocytopenia, hyponatremia, hypoproteinemia, hypoalbuminemia, hypocalcemia and acute renal failure, in one case associated with anuria. A low grade parasitemia was observed in two patients and a high grade parasitemia (20%-58% of erythrocytes) in four. Exchange transfusion was performed only in high parasitemic patients and all of them survived. All patients were treated with quinine, a sulfonamide and pyrimethamine. Additionally, five patients received oxytetracycline, doxycycline or clindamycin. Three patients required hemodyalisis. Five patients had delirium, coma or seizures. All patients had at least one sign of hepatic impairment: liver enlargement, jaundice or increased bilirubin or aminotransferase levels. Two patients had spleen enlargement. Laboratory findings suggested disseminated intravascular coagulation in four patients. Four patients developed pulmonary changes and three of them required mechanical ventilation. A Swan-Ganz catheter was placed in four patients. In three of them (two with pulmonary edema) the pulmonary capillary wedge pressure was initially increased, which suggested a cardiogenic or hypervolemia mechanism, but soon returned to normal level. One patient with low grade parasitemia died because of adult respiratory distress syndrome after 18 days. In our series, the degree of parasitemia was not related to the severity of the disease.
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PMID:[Severe and complicated malaria. Report of six cases]. 977 80

This open-label study was performed to evaluate efficacy and safety of Felbamate (FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36 patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg. Patients were monitored according to clinical practice and performed regularly laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In this study, 5% of patients resulted to be seizure-free, 11% showed a seizure reduction more than 75%, 23% decreased their seizure frequency between 50% and 75% (P = 0.0001). The adverse events which were reported more frequently were: nausea, vomiting, anorexia and weight loss. Even if the patients sample is small FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated profile.
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PMID:Felbamate in refractory partial epilepsy. 1019 11

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > or = 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.
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PMID:A pilot study of topiramate in children with Lennox-Gastaut syndrome. 1041 13

Zonisamide (ZNS) is a relatively new antiepileptic medication currently available in Japan. Attempts to market the drug in the United States were thwarted by reports of nephrolithiasis by European and American investigators. However, successful marketing of the drug in Japan has resulted in a renewed interest in bringing the drug to the United States. Japanese experience with ZNS showed a broad spectrum of efficacy in the treatment of seizures, including infantile spasms and myoclonic seizures. A neuroprotective role and an antimanic effect have also been reported. The exact antiepileptic mechanism of action of ZNS is not known, but it has dose-dependent sodium channel blocking and T-type calcium channel blocking properties and free radical scavenging actions. Recommended initial adult dosage in Japan is 100-200 mg/d, increased if necessary to 200-400 mg/d, up to a maximum of 600 mg/d. In children, initial dosage is 2-4 mg/kg/d, increased if necessary to 4-8 mg/kg/d up to a maximum of 12 mg/kg/d. The recommended therapeutic plasma ZNS concentration is 10-20 mg/L. Adverse events, most notably drowsiness, loss of appetite, gastrointestinal problems, and CNS toxicity, have been noted with plasma ZNS concentrations of > 30 mg/L. A drug rash also has been reported.
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PMID:Zonisamide: a new antiepileptic drug. 1044 47

A 3-day-old infant presented with anorexia, irritability, hypotonia, and seizures. Blood ammonia was 2115 micromol/L and amino and organic acid analyses were consistent with ornithine transcarbamylase deficiency. Liver biopsy confirmed only 1% enzyme activity. The patient was treated with hemodialysis. An electroencephalogram (EEG) revealed multifocal independent spike-and-sharp-wave discharges. After initial stabilization he was placed on a low-protein diet with citrulline and phenylbutyrate. Conjugating agents (arginine, sodium benzoate, and sodium phenylacetate) have been added during periods of metabolic decompensation. Although developmentally delayed, the patient has shown signs of clinical improvement and EEG activity has likewise improved with only mild background slowing and no evidence of epileptogenic activity at 4 years of age. A second infant presented at 3 days of age with a similar history, blood ammonia of 1382 micromol/L, and metabolic studies indicative of ornithine transcarbamylase deficiency. EEG showed multifocal independent ictal and interictal discharges. Electrographic abnormalities persisted despite lowering of blood ammonia with hemodialysis and conjugating agents. The patient continued to decline clinically and died on the 7th hospital day. EEG changes parallel the clinical course of ornithine transcarbamylase deficiency and may serve as an objective marker of the effectiveness of therapeutic interventions.
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PMID:Electroencephalographic findings in ornithine transcarbamylase deficiency. 1045 65

A 3-year retrospective review was undertaken of the use of topiramate in 51 children aged 3-16 years with partial and generalized epilepsies who attended a tertiary referral epilepsy centre in a large children's hospital. The mean follow-up period was 19 months (range 6-33 months). Twenty-six children (51%) were still receiving topiramate at the time of their last review. Fifteen children (29%) showed a greater than 50% reduction in their seizure frequency and four children (8%) became seizure free, three on topiramate monotherapy. The drug appeared to be most effective in children with moderate learning difficulties with 75% showing an improvement in seizure control compared with 25% of children with normal educational functioning. Topiramate was withdrawn in 25 patients. The reasons for withdrawal included adverse effects in 20, lack of effect in three and worsening of seizures in two patients. Adverse side effects were reported in 57% of the 51 patients. The majority of the side effects were related to behavioural and cognitive difficulties, with less-common side effects including anorexia, weight loss and headaches.
Seizure 2000 Mar
PMID:Efficacy and tolerability of topiramate in childhood and adolescent epilepsy: a clinical experience. 1084 39


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