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

Lamotrigine is a novel antiepileptic that, although its mechanism is not completely understood, appears to affect voltage-activated sodium channels, resulting in inhibition of the presynaptic release of the excitatory neurotransmitter glutamate. It is well absorbed after oral administration. Its route of elimination is hepatic glucuronidation, which is susceptible to both hepatic microsomal enzyme-inducing and -inhibiting agents. In clinical trials lamotrigine was effective as add-on therapy for refractory partial seizures in adults. Small trials suggest the feasibility of monotherapy, but further controlled trials are warranted to support this practice. Additional data indicate the utility of lamotrigine for generalized seizures. Reported side effects are rash, nausea, vomiting, blurred vision, diplopia, and vision abnormalities. Lamotrigine appears to be an attractive alternative to currently available antiepileptics.
 ...
PMID:Lamotrigine. 762 59

Lamotrigine is an antiepileptic drug which is believed to suppress seizures by inhibiting the release of excitatory neurotransmitters. Efficacy has been demonstrated for lamotrigine as add-on therapy to existing regimens in patients with resistant partial seizures. Total seizure frequency was reduced by 17 to 59% compared with placebo, and 13 to 67% of patients experienced reductions of > or = 50% in seizure frequency. Secondarily generalised tonic-clonic seizures respond well to lamotrigine, and there is preliminary evidence of improvement in patients with primary generalised seizures, Lennox-Gastaut syndrome and in children with multiple seizure types. Seizure control has been maintained in patients who have continued to receive lamotrigine as monotherapy after discontinuation of other medications. Results of one trial suggest similar efficacy for lamotrigine monotherapy as for carbamazepine, but confirmation of its use in this setting awaits more extensive controlled comparisons with established agents. Adverse events associated with lamotrigine as add-on therapy are typical of antiepileptic drugs, namely dizziness, ataxia and other CNS-related symptoms. Rash, which has occurred in 10% of patients in placebo-controlled trials, may be severe and its appearance has led to discontinuation of therapy in 1% of patients. Lamotrigine appears well tolerated in the longer term, but this facet of its profile requires further monitoring. Influences of valproic acid and enzyme-inducing anti-epileptics on lamotrigine eliminate necessitate dosage modification of lamotrigine. Conversely, lamotrigine has little apparent influence on the pharmacokinetics of other agents, although it may increase plasma concentrations of the active metabolite of carbamazepine during concomitant administration. Thus, lamotrigine permits improved seizure control in some patients with refractory partial seizures, and may prove to be especially effective in secondarily generalised tonic-clonic seizures. As is usual at this stage in a drug's development, several aspects of the profile of lamotrigine are incompletely defined, notably its efficacy in other seizure types, in children, as monotherapy, and its longer term tolerability. Nonetheless, lamotrigine presently offers a worthwhile alternative for the physician confronted with the challenge of treating patients with intractable partial seizures with or without secondarily generalised seizures, and shows potential for broader applications in other areas of epilepsy management.
 ...
PMID:Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. 769 4

Lamotrigine has been licensed widely as adjunctive therapy for partial and secondary generalised seizures. Use of the drug as monotherapy was investigated in a double-blind, randomised, parallel-group comparison with carbamazepine in newly diagnosed epilepsy. After 4 weeks of planned, fixed dose escalation, doses were adjusted according to efficacy, adverse events, and plasma concentrations. 151 of 260 patients (131 lamotrigine, 129 carbamazepine) in eight UK centres completed the 48-week trial. No differences in efficacy between the drugs were found for partial seizures with or without secondary generalisation or for primary generalised tonic-clonic seizures. The proportion of patients maintained seizure-free during the last 24 weeks of treatment was almost the same in both groups (39% lamotrigine, 38% carbamazepine). More patients with primary generalised tonic-clonic seizures (47% both groups) than those presenting with a focal onset (35%, 37%) were fully controlled. Overall, fewer patients on lamotrigine than on carbamazepine withdrew because of adverse events (15 vs 27%). The commonest side-effect leading to withdrawal with either drug was rash (9%, 13%). Sleepiness was less common in lamotrigine than in carbamazepine recipients (12 vs 22%, p < 0.05). More lamotrigine than carbamazepine recipients (65 vs 51%, p = 0.018) completed the study (hazard ratio 1.57 [95% CI 1.07-2.31]). Lamotrigine and carbamazepine showed similar efficacy against partial onset seizures and primary generalised tonic-clonic seizures in newly diagnosed epilepsy. Lamotrigine, however, was better tolerated.
 ...
PMID:Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group. 774 68

Several new antiepileptic drugs offer a worthwhile alternative when standard antiepileptic drugs have failed. Suggestions have been made to improve the risk-benefit ratio of the new antiepileptic agents. More specifically, vigabatrin, which is a very useful and well tolerated new antiepileptic drug for refractory partial epilepsy, should be started at a low dosage of 0.5 g/day with increments of 0.5 g/day every week. Daily dosages exceeding 3 g/day should be restricted to patients with improvement. If necessary, the daily dosage of vigabatrin should be withdrawn slowly, i.e. by not more than 1 g/week. Lamotrigine is also a beneficial new drug for refractory partial and generalized seizures. However, the drug is associated with rash. In patients also receiving valproic acid (sodium valproate) [which inhibits the metabolism of lamotrigine], the incidence of rash can be reduced by slow titration of 25mg every other day for the first week and 25mg per day for the second week. Rare hypersensitivity reactions, e.g. Stevens-Johnson syndrome, remain a problem. The risk-benefit ratio of felbamate has recently been compromised by fatal aplastic anaemia and fatal liver disease in a number of patients. In general, patients should be withdrawn from felbamate, if possible, until further clarification of its definitive risk-benefit ratio. Finally, gabapentin is a very safe add-on medication. Its remarkably low potential to cause adverse effects makes it a welcome addition for the treatment of refractory partial epilepsy.
 ...
PMID:The new anticonvulsant drugs. Implications for avoidance of adverse effects. 772 52

Progress made in the development of new antiepileptics (AEs) is justified by the high percentage of refractory patients to the available medical therapy (25%), although only a minority of cases are deemed suitable for surgical therapy. Yet, the ideal AE, that is, with a well-known mechanism of action, effective in monotherapy for all epileptic fits, with a perfect pharmacokinetic profile, with no adverse or teratogenic effects, with no drug interactions and available under many formulations, is far from being developed. The new AEs arise either from modification of already marked drug molecules or clinical formulations or from the effectiveness on the excitatory/inhibitory balance of the major neurotransmitters involved in the pathogenesis of seizures, the gamma-amino-butyric acid (GABA) as the inhibitory, and the glutamate (GLU) as the excitatory one. However, the mechanism remains unknown in a few of them. Those new AEs already marketed in Portugal (Vigabatrin), soon to be (Lamotrigine, Oxcarbazepine) or available abroad only (Gabapentin, Zonisamide) are review with special emphasis on their pharmacokinetic profile, side effects, interaction with other AEs, and clinical use. In conclusion, these new drugs have brought a very important advancement in the management of refractory patients, but the development of well-designed comparative trials involving both monotherapy and polytherapy has become important in order to develop useful strategies in the drug management of epilepsy.
 ...
PMID:[New antiepileptic medications]. 774 11

LTG, lamotrigine is a new antiepileptic agent chemically unrelated to any established drugs in use. The safety and the efficacy of LTG (564.5 +/- 74.4) mg/day was evaluated as add-on therapy (plus CBZ) in a placebo controlled study of 34 patients with refractory partial complex and/or partial secondary generalized seizures. The incidence of adverse effects of the drug is low and the unwanted effects are reversible. The long half-life and lack of effect on other AEDs will render LTG an easily dosable addiction to a patient's existing regimen. Reduction in the total number seizures was recorded in 61.4% of patients. We conclude that LTG is an effective AED for treatment of therapy-resistant partial seizure.
 ...
PMID:[Lamotrigine: first experience in Italy]. 778 82

Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic]. 787 1

Lamotrigine, a novel antiepileptic drug thought to inhibit the excitatory neurotransmitter release and indicated for convulsive seizures, was tested for its efficacy in modulating non-convulsive seizures of the absence type of epilepsy. This was done in a rat model for absence epilepsy: the WAG/Rij strain of rats. In side-effect free doses, lamotrigine did not inhibit absence seizures in these animals. Only in a high dose a reduction of spike-wave activity was noticed, but in that dose side-effects such as abnormal locomotion, were also seen. These findings underline the differential pharmacological profile of convulsive and non-convulsive generalized epilepsy.
 ...
PMID:Effects of lamotrigine on absence seizures in rats. 789 36

Neuropsychological dysfunction in children and adults with epilepsy is common and has several possible interrelated causes, including the underlying pathophysiology, possible cerebral pathology, the effects of subclinical discharges, sleep disorders, status epilepticus and drug therapy. Of these factors the effects of subclinical discharges and those of medication are potentially remediable. In up to 50% of patients with subclinical epileptiform EEG discharges, these are associated with transitory cognitive impairment. When the discharges are focal, the cognitive deficits usually reflect the normal neuropsychological functions of the affected brain region. Most antiepileptic drugs, with the exception of the benzodiazepines (which themselves adversely affect cognition) and lamotrigine, do not suppress inter-ictal discharges. Although well-designed clinical trials of the effects of antiepileptic drugs are difficult to perform, there is convincing evidence that phenobarbitone and phenytoin cause cognitive impairment. Drugs which control both the seizures and inter-ictal discharges should improve cognitive function, provided the drugs themselves do not have a cognitive penalty. Lamotrigine provides effective control of both overt and subclinical seizures, without adversely affecting cognition.
Seizure 1994 Dec
PMID:Cognitive impairment--is it inevitable? 789 46

Lamotrigine is an anticonvulsant chemically related to the antifolate compound pyrimidine. In the maximal electroshock test in rodents it is more potent and has a longer duration of action than other anticonvulsants, and it exhibits little acute neurotoxicity. Lamotrigine suppresses sustained repetitive firing by prolonging inactivation of the sodium channel in the neuronal membrane. It blocks the pathological, but not the normal, release of glutamate and aspartate. Lamotrigine is also cerebroprotective in rodent models of stroke or focal ischaemia. This effect correlates with the suppression of glutamate release and is probably due principally to the action on sodium channels. Lamotrigine has a favourable pharmacokinetic profile. It is rapidly and completely absorbed and has linear pharmacokinetics. Protein binding is moderate and, as lamotrigine does not induce liver enzymes, it does not alter the pharmacokinetics of other anticonvulsants. The half-life and clearance of lamotrigine are altered by concomitant antiepileptic therapy. In the presence of the enzyme inhibitor sodium valproate the half-life is doubled and this interaction is clinically significant.
Seizure 1994 Dec
PMID:Lamotrigine--a novel approach. 789 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>