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)

Lamotrigine (LTG) as both effective against a wide range of seizure types and epileptic syndromes and well tolerated drug is being used in mono--as well as in polytherapy of pharmacoresistant epilepsy. The aim of this study was to evaluate the efficacy, safety and neuropsychological functioning after LTG (mean daily dose: 316 mg) as long-term monotherapy (12 mo) in 24 young adult out-patients (22.5 ys) with newly recognised and not-previously treated epilepsy in an open, non-comparative trial. 67% of patients were responders (above 50% reduction in seizure frequency) and 42% reported seizures remission. The best were results in patients with generalised convulsive fits (87% with remission). Adverse events in the early phase of medication in 21% of patients typically concerned CNS and gastrointestinal system (headache, asthenia, insomnia, nausea, gastric aches) and resolved spontaneously without treatment discontinuation. Biochemical examinations were normal and transient leucopenia and diminishion of MCV were clinically not significant. Neurodynamic abilities, neuropsychological examination results, memory verbal and visual tests and organic evaluation in organic triada tests did not show deterioration after LTG treatment. Slight difficulties in abstractive and operative thinking and some focal symptoms of fronto-temporal origin should be considered a result of drug but also the epilepsy per se. No significant differences in latencies and amplitudes of evoked potentials (VEP, BAEP, SEP and especially ERP-300) were measured after LTG. Preliminary results obtained in this study supported good efficacy and tolerability and especially lack of unfavourable influence of LTG on neuropsychological functioning in young previously untreated patients with epilepsy.
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PMID:Long-term monotherapy with lamotrigine in newly diagnosed epilepsy in adults. 1197 53

Sarin (O-isopropylmethylphosphonofluoridate) is a highly toxic nerve agent produced for chemical warfare. Sarin is an extremely potent acetylcholinesterase (AchE) inhibitor with high specificity and affinity for the enzyme. Death by sarin is due to anoxia resulting from airway obstruction, weakness of the muscles of respiration, convulsions and respiratory failure. The main clinical symptoms of acute toxicity of sarin are seizures, tremors and hypothermia. Exposure to sarin during incidents in Japan in 1994, 1995 and 1998, and possible exposure to low levels of sarin during the Gulf War, resulted in the deaths and injury of many people in Japan and caused possible long-term health effects on Gulf War veterans. Symptoms related to sarin poisoning in Japan still exist 1-3 years after the incident and include fatigue, asthenia, shoulder stiffness and blurred vision. Sarin produced seizures in rats and pigs. Recent studies showed that long-term exposure to low levels of sarin caused neurophysiological and behavioral alterations. Toxicity from sarin significantly increased following concurrent exposure to other chemicals such as pyridostigmine bromide. Further research to examine effects of sarin on the cellular and the molecular levels, gene transcription, endocrine system as well as its long-term impact is needed.
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PMID:Sarin: health effects, metabolism, and methods of analysis. 1238 97

Levetiracetam has recently been licensed in Europe and the U.S.A. for use as an adjunctive agent in partial epilepsy with or without secondary generalization. The mode of action has yet to be elucidated, but may involve a new brain-specific binding site, the ligand for which is unknown. Levetiracetam has a favorable pharmacokinetic profile, with rapid and almost complete oral absorption, almost 100% bioavailability, linear, dose-dependent maximum plasma concentrations and minimal plasma protein binding. Excretion is mainly renal, with most of the drug being eliminated unchanged. Levetiracetam does not have an effect on the major drug-metabolizing hepatic enzymes, and thus is associated with a low incidence of interactions with other antiepileptic drugs (AEDs). These properties make it a well-tolerated drug, with the most common reported side effects being asthenia, somnolence, headache and dizziness. Antiepileptic properties of levetiracetam demonstrated in animal studies have been borne out by large double-blind, placebo-controlled clinical trials, with significantly improved responder rates (>/= 50% reduction in seizure frequency from baseline) and number of seizure- free patients versus placebo. In addition, efficacy appears to be maintained over the long term and no evidence for the development of tolerance to the effects of levetiracetam has been seen. (c) 2001 Prous Science. All rights reserved.
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PMID:Levetiracetam: A new antiepileptic drug for the adjunctive therapy of chronic epilepsy. 1273 64

The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study is a continuing phase IV open-label evaluation of the antiepileptic drug levetiracetam (Keppra) as an adjunctive therapy in adult patients with uncontrolled partial seizures. The study, which began in April 2000, is scheduled to include 1400 patients from 300 centres in 16 countries. An interim analysis of the first 731 patients from 117 centres in nine countries treated over a 16-week period showed that seizure frequency was reduced by half or more in 49% of patients across all seizure types. A substantial 17.2% of patients achieved complete freedom from seizures. Levetiracetam was well tolerated overall. Adverse events were predominantly mild to moderate and rarely led to discontinuation. The most commonly reported symptoms were asthenia, somnolence, headache and dizziness.
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PMID:The SKATE study: interim analysis. 1291 96

Dexamethasone-cyclophosphamide pulse (DCP) is the prefered mode of therapy in pemphigus in India because it is relatively free from the side effects seen with heavy doses of daily oral steroids. One hundred forty-six pemphigus patients treated with DCP were observed for side effects of this regimen. One hundred forty mg of dexamethasone was administered IV in 200 ml of 5% dextrose over a period of 60-90 minutes on 3 consecutive days. Five hundred mg of cyclophosphamide was added on first day of the pulse and 50 mg given orally daily in the intervening period. DCP was repeated every 4 weeks and continued for 6 months after subsidence of the disease (no new lesions). Flushing over the face was the most common event recorded during the adiministration in 78 subjects followed by palpitations in 11, hiccups in 9, and numbness of feet in 6. Fourteen patients had polyurea, and 3 developed skin rash. Shivering, shooting pains along thighs, breathlessness, seizure and unilateral limb edema were observed in one patient each. Generalized weakness/malaise was the most troublesome delayed side effect in 81 (55.4%) patients; it lasted for 8-15 days after the pulse. Thirty-six (24.6%) had inadequate sleep syndrome, 23 (15.7%) had headache, 21 (14.3%) complained of arthralgias, 19 (13%) experienced alteration in taste, and 13 (9%) had diffuse hair loss. 28 females developed menstrual disturbances, and 14 (9.5%) had blurring of vision (glaucoma in 3 and posterior subcapsular cataract in 1). Thirteen of eighteen diabetics had an increase in blood sugar requiring higher doses of insulin. Five NIDDM patients needed insulin. Four (2.7%) developed hypertension. Pulse therapy is not absolutely free from side effects. Hypertension and diabetes occur less frequently as compared to conventional steroid therapy. Generalized weakness, flushing, headache and taste alteration occur exclusively with pulse therapy.
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PMID:Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. 1468 52

Tiagabine inhibits gamma-aminobutyric acid uptake into neurons and glia. This mechanism of action is specific and unique among the antiepileptic drugs (AEDs). Tiagabine is efficacious in animal seizure models at subtoxic doses. There is no evidence of clinically important teratogenicity, carcinogenicity or mutagenicity in animals treated acutely or chronically with tiagabine. Tiagabine has no clinically relevant effect on hepatic metabolism or serum levels of other AEDs, has no clinically significant effects on laboratory values and has not been shown to have any clinically important interactions with common non-AEDs. Tiagabine has linear, predictable pharmacokinetics that do not vary significantly with age. Adverse effects are usually mild to moderate in severity and almost always resolve without medical intervention. The most common adverse events in controlled studies are dizziness, asthenia, somnolence, accidental injury, infection, headache, nausea and nervousness. Tiagabine is effective as add-on therapy for partial seizures in patients with medically refractory epilepsy in doses ranging from 32-56 mg daily. Despite its short half-life of 2-3 hours in patients on enzyme-inducing AEDs, tiagabine is effective when dosed 2-3 times a day. Conversion to tiagabine monotherapy can be achieved in patients with medically refractory epilepsy, though additional studies are needed to establish the effective dosage range. The introduction of drugs like tiagabine that have known mechanisms of action which differ from existing treatments further increases the range of options for patients with epilepsy.
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PMID:Tiagabine. 1509 57

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.
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PMID:Benefit-risk assessment of levetiracetam in the treatment of partial seizures. 1618 Sep 37

Ifosfamide can be responsible for acute central neurotoxicity in children and adolescents treated for cancer. The signs of acute encephalopathy most frequently observed are: alteration of consciousness, cerebellar syndrome, asthenia, urinary incontinence, cranial nerve palsy, and seizures. Various combinations of these signs may occur, but disorders of consciousness and drowsiness are common. We describe the case of a young man presenting with reversible acute hypomanic disorder during ifosfamide-based chemotherapy and discuss the possible mechanisms of this toxicity.
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PMID:Ifosfamide neurotoxicity: an atypical presentation with psychiatric manifestations. 1626 98

The aim of this study was to assess the relationship between levetiracetam dose and both efficacy and safety in adult patients with refractory partial epilepsy. Dose-response relationships for levetiracetam efficacy were evaluated using pooled data from three trials including adults with refractory partial epilepsy. Two were randomized, double-blind, placebo-controlled, parallel-group trials in which doses of 1000-3000 mg/day of levetiracetam were administered as adjunctive therapy. The third consisted of the two parts of a crossover randomized, double-blind study in which levetiracetam (1000 or 2000 mg/day) or placebo was added to ongoing therapy. Data from each part of the crossover trial were included as if it was an independent parallel-group study. A fourth randomized double-blind trial was added for the safety evaluation. It included data from adults receiving placebo or 2000 mg/day of levetiracetam as adjunctive therapy for refractory partial seizures. The combined analysis showed an increasing effect with increasing dose. The responder rates (> or = 50% reduction in seizures) for placebo and levetiracetam 1000, 2000, and 3000 mg/day were 13.1%, 28.5%, 34.3%, and 41.3%, respectively. The respective values for seizure freedom were 0.8%, 4.7%, 6.3%, and 8.6%. There was no evidence of a dose-response relationship with regard to adverse events, including those (asthenia, dizziness, somnolence) most commonly associated with this antiepileptic drug. Patients who do not become seizure-free at the lowest recommended levetiracetam dose (1000 mg/day) should be titrated to 2000 or 3000 mg/day to provide the greatest opportunity for efficacy with little or no increased risk for adverse events.
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PMID:Assessment of a dose-response relationship of levetiracetam. 1693 Mar 58

Levetiracetam is an antiepileptic drug approved for use as an adjunct agent in partial-onset seizures in adults and children aged > or = 4 years. It was also approved as adjunctive therapy in the treatment of adults and adolescents aged > or = 12 years with juvenile myoclonic epilepsy. A parenteral intravenous formulation has recently become available allowing for its use when oral administration is temporarily not feasible. Available literature has demonstrated and supported that levetiracetam has an acceptable safety profile and this review discusses the safety profile of levetiracetam, with attention to special populations. The most common adverse effects are somnolence, asthenia and dizziness, which usually appear early after initiation of levetiracetam therapy and generally resolve without medication withdrawal. The most serious adverse effects are behavioral in nature and are more common in children and in patients with a prior history of behavioral problems.
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PMID:The safety of levetiracetam. 1748 Jan 74


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