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)

Although older generation antiepileptic drugs (AEDs) such as carbamazepine, phenytoin and valproic acid continue to be widely used in the treatment of epilepsy, these drugs have important shortcomings such as a highly variable and nonlinear pharmacokinetics, a narrow therapeutic index, suboptimal response rates, and a propensity to cause significant adverse effects and drug interactions. In an attempt to overcome these problems, a new generation of AEDs has been introduced in the last decade. Compared with older agents, some of these drugs offer appreciable advantages in terms of less variable kinetics and, particularly in the case of gabapentin, levetiracetam and vigabatrin, a lower interaction potential. Lamotrigine, topiramate, zonisamide and felbamate protect against partial seizures and a variety of generalized seizure types, vigabatrin is effective against partial seizures (with or without secondary generalization) and infantile spasms, while the use of oxcarbazepine, tiagabine and gabapentin is mainly restricted to patients with partial epilepsy (and, in the case of oxcarbazepine, also primarily generalized tonic-clonic seizures). Levetiracetam, the latest AED to be introduced, has been found to be effective in partial seizures, but its potentially broader efficacy spectrum remains to be determined in clinical studies. Currently, the main use of new generation AEDs is in the adjunctive therapy of patients refractory to older agents. However, due to advantages in terms of tolerability and ease of use, some of these drugs are increasingly used for first-line management in certain subgroups of patients. Due to serious toxicity risks, felbamate and vigabatrin should be prescribed only in patients refractory to other drugs. In the case of vigabatrin, however, first line use may be justified in infants with spasms.
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PMID:Clinical pharmacology and therapeutic use of the new antiepileptic drugs. 1186 May 29

1. The tetanus toxin seizure model, which is associated with spontaneous and intermittent generalized and non-generalized seizures, is considered to reflect human complex partial epilepsy. The purpose of the present study was to investigate and compare the anticonvulsant effects of carbamazepine with that of levetiracetam, a new anti-epileptic drug in this model. 2. One microl of tetanus toxin solution (containing 12 mLD(50) microl(-1) of tetanus toxin) was placed stereotactically into the rat left hippocampus resulting in generalized and non-generalized seizures. 3. Carbamazepine (4 mg kg(-1) h(-1)) and levetiracetam (8 and 16 mg kg(-1) h(-1)) were administered during a 7 day period via an osmotic minipump which was placed in the peritoneal cavity. Carbamazepine (4 mg kg(-1) h(-1)) exhibited no significant anticonvulsant effect, compared to control, when the entire 7 day study period was evaluated but the reduction in generalized seizures was greater (35.5%) than that for non-generalized seizures (12.6%). However, during the first 2 days of carbamazepine administration a significant reduction in both generalized seizure frequency (90%) and duration (25%) was observed. Non-generalized seizures were unaffected. This time-dependent anticonvulsant effect exactly paralleled the central (CSF) and peripheral (serum) kinetics of carbamazepine in that steady-state concentrations declined over time, with the highest concentrations achieved during the first 2 days. Also there was a significant 27.3% reduction in duration of generalized seizures during the 7 day study period (P=0.0001). 4. Levetiracetam administration (8 and 16 mg kg(-1) h(-1)) was associated with a dose-dependent reduction in the frequency of both generalized (39 v 57%) and non-generalized (36 v 41%) seizures. However, seizure suppression was more substantial for generalized seizures. Also a significant dose-dependent reduction in overall generalized seizure duration was observed. 5. These data provide experimental evidence for the clinical efficacy of levetiracetam for the management of patients with complex partial seizures. Furthermore, levetiracetam probably does not act by preventing ictogenesis per se but acts to reduce seizure severity and seizure generalization.
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PMID:A comparison of the efficacy of carbamazepine and the novel anti-epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy. 1190 55

Levetiracetam (Keppra--UCB Pharma) is a new anti-epileptic drug, marketed in the UK since 2000. It is licensed for use as adjunctive treatment for partial seizures, with or without secondary generalisation, in people aged over 16 years. The company claims that levetiracetam is "highly effective", with a "therapeutic starting dose", "excellent tolerability", and "no known drug/drug interactions". Here, we discuss the place of levetiracetam in the treatment of patienTs with epilepsy.
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PMID:Levetiracetam--a new drug for epilepsy. 1199 65

Anticonvulsants are frequently used in the treatment of paroxysmal kinesiogenic choreoathetosis (PKC). Although they are often extremely effective in eliminating paroxysmal movements, short- and long-term side-effects may limit their use in young patients. Levetiracetam (Keppra), a novel antiepileptic drug approved for the treatment of partial seizures is well tolerated in patients with epilepsy. We report on the use of levetiracetam in the treatment of PKC. Levetiracetam was effective in eliminating paroxysmal events and should be considered as an alternative to standard antiepileptic medications in this disorder.
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PMID:Levetiracetam in the treatment of paroxysmal kinesiogenic choreoathetosis. 1211 21

Levetiracetam, one of the newer-generation antiepilepsy drugs, is not currently approved for use in children. Given its favorable efficacy, pharmacokinetic, and, particularly, safety profile in adults, we felt that it may be a useful antiepilepsy drug for children with refractory epilepsy. We treated 39 patients (mean age 8.6 years) with open-label levetiracetam for up to 9 months. Seizure frequency, drug dosages, adverse events, and neurologic examinations were documented at baseline and routine follow-up visits. Levetiracetam, as add-on therapy, was effective in reducing seizure frequency in a variety of seizure types but was most effective for partial-onset seizures. Fourteen patients were discontinued for lack of efficacy or adverse events. Ten patients reported improvements in cognition or behavior. Levetiracetam was generally effective and well tolerated in this open-label study. Its apparent positive effects on cognition in some patients are encouraging. Large, well-controlled studies are needed to fully define levetiracetam's potential in children with refractory epilepsy.
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PMID:Levetiracetam in refractory pediatric epilepsy. 1217 60

This study compared levetiracetam (Keppra) with reference antiepileptic drugs (AEDs) in the rat pilocarpine model of temporal lobe epilepsy. Electroencephalogram (EEG) recordings showed that i.p. administration of valproate (300 mg/kg), phenobarbital (5 mg/kg) and clonazepam (0.5 mg/kg) all significantly delayed the appearance of the first epileptic spike discharge in hippocampus as well as synchronous epileptiform activity in hippocampus and cortex. In contrast, i.p. administration of levetiracetam (17 mg/kg) only significantly delayed the appearance of the latter. This was corroborated by findings showing that i.p. administration of levetiracetam (17 mg/kg) significantly opposed pilocarpine-induced increases in the amplitude of the orthodromic population spike in the hippocampal CA3 area of urethane-anaesthetised rats, while valproate (200 mg/kg), phenobarbital (10 mg/kg) and clonazepam (1 mg/kg) had no effect. Pre-treatment i.p. with phenobarbital (10 mg/kg) and clonazepam (0.5 mg/kg) significantly reversed seizure-induced changes in aspartate and GABA concentrations while valproate (300 mg/kg) significantly reduced aspartate concentrations further. In contrast, levetiracetam (34 mg/kg) significantly counteracted all seizure-induced alterations in amino acid concentrations. Midazolam induced significant seizure protection after microinjection into substantia nigra pars reticulata (SNR, 50 nmol), nucleus accumbens (NA, 25 nmol) and caudate putamen (CP, 25 nmol), whereas phenytoin (50 nmol) only showed significant seizure protection after injection into the latter area. Levetiracetam differed by significant seizure protection after injection into SNR (1,000 nmol) and NA (3,000 nmol). These results suggest that levetiracetam is distinct from other AEDs by its ability to selectively suppress synchronisation of neuronal spike and burst firing in hippocampus.
Seizure 2003 Mar
PMID:Electrophysiological, neurochemical and regional effects of levetiracetam in the rat pilocarpine model of temporal lobe epilepsy. 1256 32

Epilepsy is a common comorbidity among developmentally disabled (DD) patients, and special considerations apply to its treatment. In particular, clinicians should try to avoid antiepileptic drugs (AEDs) with sedating properties or adverse cognitive effects that might further diminish quality of life for DD patients. Behavioral changes due to medication and significant pharmacokinetic interactions with other medications are also concerns. The newer AEDs, approved in the 1990s, offer new options for the treatment of individuals with developmental disability and epilepsy. Gabapentin does not interact with the hepatic metabolism of other AEDs or psychotropic agents, results in a statistically significant reduction in seizure frequency in mentally retarded children, and is generally well tolerated. Felbamate is an effective broad-spectrum AED, but has serious toxicity issues limiting its use. Lamotrigine has been extensively studied in the DD population, achieving seizure reduction rates of up to 50% in some trials. Although it is usually well tolerated in this population, its pharmacokinetic profile is influenced by concomitant medications. Levetiracetam has been found to be effective against kindled seizures and has been approved as adjunctive therapy for partial epilepsies. It does not cause any pharmacokinetic interactions, but may have behavioral side effects. Oxcarbazepine is a homologue of carbamazepine that has fewer drug interactions. It is approved for mono- or adjunctive therapy in patients with partial seizures, and its use in DD individuals appears to be worthwhile. Tiagabine is extensively bound to plasma proteins and is therefore subject to protein-binding displacement interactions by other highly protein-bound drugs, such as sodium valproate. While there are trial data showing its efficacy as adjunctive therapy in partial epilepsy in adults and children, there is a paucity of data specific to the DD population. Common side effects include sedation. Topiramate is a broad-spectrum AED approved as adjunctive therapy for partial and primary generalized tonic-clonic seizures. It appears to be particularly effective in patients with Lennox-Gastaut syndrome and those with cognitive disabilities. It appears to be better tolerated in the DD population than in the general population. Zonisamide has been effective in the DD population, yielding a seizure reduction of 50% in 41% of children in 1 trial. It has been associated with renal stone formation, sedation, and cognitive effects, however. The new AEDs have a role in treating seizures in the DD. Side effects that limit their use include anorexia, behavioral changes, and sedation. Seizure exacerbation can occur with the new AEDs and success is defined empirically and by improvements in quality of life.
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PMID:Antiepileptic drug treatment in the developmentally disabled: treatment considerations with the newer antiepileptic drugs. 1260 9

Levetiracetam is a new anti-convulsant with impressive pivotal trial credentials. We examined its effectiveness in refractory clinic patients with epilepsy with a year's follow up. Six months after initiation 32% of the patients were seizure free, and 26% at one year. By the end of the 12 months follow up 77% of patients were still taking the drug, having gained benefit from it: 23% had dropped out due to intolerable side effects, seizure increase or lack of efficacy. There is evidence that the drug is broad spectrum and as effective in primary generalised epilepsy as in partial onset epilepsy. Our audit of its use and effectiveness has led us to position it as our first choice add-on drug if the initial monotherapy drug fails.
Seizure 2003 Apr
PMID:Clinical experience of marketed Levetiracetam in an epilepsy clinic-a one year follow up study. 1265 Oct 77

Objective. Seizures in developmentally disabled are often refractory to treatment. This study aimed to expand the clinical experience with levetiracetam as an antiepileptic drug (AED) for this population.Methods. Four males and two females (aged 25-51) with mental retardation requiring institutionalization and uncontrolled seizures (1.7-12.2/month) received levetiracetam (0.5-2.5g/day) in addition to their standard AEDs. Clinical response was closely followed for 4-10 months (mean, 6 months) with respect to seizure control and adverse effects.Results. Two of the patients became seizure-free, while the other four had seizure reductions ranging from 71 to 92%. None of the patients experienced adverse effects, and three had improvements in behavior.Conclusions. Levetiracetam may be extremely effective in patients with developmental disability. Behavioral abnormalities improved in 50% of the patients.
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PMID:Efficacy of levetiracetam in developmentally disabled patients: a review of the literature and six case reports. 1266 10

Levetiracetam is the latest in a series of nine new antiepileptic drugs (AEDs) to be licensed for clinical use. Its present license is for use as adjunctive therapy for the treatment of patients with partial seizures with or without secondary generalization that are refractory to other established first line AEDs. Pharmacokinetic studies of levetiracetam have been conducted in healthy volunteers, in patients of all ages with epilepsy, and in certain special populations. Results of these studies indicate that levetiracetam has a very favorable pharmacokinetic profile, characterized by excellent oral absorption and bioavailability (> 95%) and a mean elimination half-life in adults, children and the elderly of 7, 6 and 10.5 h, respectively. Levetiracetam is not bound to plasma proteins and is not metabolized in the liver, so it is not expected to be associated with significant pharmacokinetic interactions. Indeed, to the best of the author's knowledge, no clinically relevant pharmacokinetic interactions with levetiracetam have yet been identified. However, pharmacodynamic interactions with carbamazepine and topiramate have been highlighted. As levetiracetam is primarily excreted unchanged in urine, dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Overall, the pharmacokinetic characteristics of levetiracetam can be considered highly desirable.
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PMID:The pharmacokinetic characteristics of levetiracetam. 1273 58


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