Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Felbamate is currently being developed as an antiepileptic agent. Although its mechanism of action has yet to be fully elucidated, felbamate appears to inhibit both the spread of seizures and increase seizure threshold in animal models. Data available in the clinical setting provide evidence that, at doses of up to 3600 mg/day as an adjunct to existing antiepileptic therapy or as monotherapy following substitution for other medications, the drug reduces the frequency of partial onset seizures in adult patients refractory to conventional antiepileptic treatments. Felbamate is also effective in the treatment of Lennox-Gastaut syndrome in children, a severe epilepsy which is usually refractory to antiepileptic agents. The effect of felbamate in the treatment of generalised tonic-clonic seizures in adults with partial onset seizures which are secondarily generalised is promising but requires clarification in large-scale trials. The most common adverse effects occurring during administration of felbamate are mild to moderate gastrointestinal (nausea, vomiting and anorexia) and central nervous system (headache, somnolence, diplopia, dizziness and insomnia) disturbances. Drug interactions with other antiepileptic agents may prove problematic in terms of adverse effects. Thus, at this stage of its development, the antiepileptic efficacy of felbamate in treatment-refractory patients with partial onset seizures and Lennox-Gastaut syndrome has been proven but efficacy in generalised tonic-clonic seizures requires further substantiation in large well controlled and well designed clinical trials. In addition, a more comprehensive base of comparative clinical trials data is necessary to further clarify issues of relative efficacy and tolerability compared with other antiepileptic agents. The clinical implications of the drug interactions associated with felbamate also require more detailed investigation. These data will be awaited with interest and when available will help to place felbamate in perspective in the management of epilepsy.
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PMID:Felbamate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy. 769 93

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.
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PMID:Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. 769 4

Lamotrigine (LTG) inhibits repetitive high frequency firing in depolarised neurones by selectively prolonging slow inactivation of the sodium channel, thereby suppressing the release of excitatory amino acids. It has been shown to be effective in 11 pivotal double-blind add-on trials in patients with refractory partial seizures with or without secondary generalisation. Subsequent anecdotal data support its efficacy for typical and atypical absences, myoclonic jerks, tonic or clonic seizures, Lennox-Gastaut syndrome and infantile spasms. Most recently LTG has been compared with carbamazepine and phenytoin in double-blind trials in patients with newly diagnosed partial and primary and secondary generalised tonic-clonic seizures. At the doses used, its efficacy was similar to the older agents for all seizure types, but LTG was better tolerated than both of the older agents. The commonest side-effects with LTG include headache, nausea, diplopia, dizziness, ataxia and tremor. Rash occurs in fewer than 5% patients. Its incidence can be reduced by starting treatment with a low dose, particularly in patients receiving concomitant sodium valproate which inhibits LTG metabolism. Enzyme inducers, such as carbamazepine, phenytoin and phenobarbital, accelerate its elimination, but LTG itself has no effect on hepatic metabolic processes. A pharmacodynamic interaction with carbamazepine necessitates a dosage reduction in some patients when LTG is introduced. LTG is a new antiepileptic agent with a long elimination half-life, a broad spectrum of activity, and a wide therapeutic ratio.
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PMID:Lamotrigine--an update. 895 Dec 13

The introduction on the French market of vigabatrin, gabapentin and lamotrigine has considerably diversified our conventional therapeutical schemes in epilepsies, as will be as amplified by the arrivals of topiramate, tiagabine and oxcarbazepine. Compared to the conventional drugs, these new products present more favorable pharmacokinetics, no or very weak interactions and a better tolerability, specially regarding the cognitive field. They should be used according to their spectrum of activity, function of their modes of action. In add-on trials on partial epilepsy patients all these new products have shown efficacy on partial and secondarily generalized seizures. Seizure frequency is reduced by at least 50 p. 100 in 30 to 50 p. 100 of the patients. A substantial number of patients can be rendered seizure-free with vigabatrin. Lamotrigine has a broader spectrum, as it is also efficacious on the different seizure types of generalized, symptomatic or idiopathic epilepsies. Main adverse events are non-specific central nervous system disturbances such as dizziness, drowsiness, ataxia, tremor or diplopia. More specifically, vigabatrin may induce weight gain and requires closer supervision in case of psychiatric history; lamotrigine which has also probable antidepressant properties, may induce skin rashs, rarely severe. Further data are needed for gabapentin which is now used at daily dosages which are two to three times those used in the initial studies. Gabamimetic agents may be worsening in some cases of generalized epilepsies, more specially on absence and myoclonic seizures. The most obvious benefits, some patients becoming seizure-free, are obtained in cases of intermediate severity, with a bitherapy including one of these new drugs. Developments in children are often delayed. Nevertheless the prognosis, including cognitive outcome, is considerably improved in infantile spasms with vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the latter being highly toxic. For the moment in France, authorities have limited the use of all these new antiepileptic drugs to adjunctive therapy in epilepsies resisting to conventional drugs. But recent monotherapy data show similar efficacy with better tolerability. Once the pivotal, controlled studies have enabled to obtain regulatory approval, all these compounds must undergo a large-scale evaluation phase in order to better define dosages, long-term tolerability, indications and eventual contra-indications in the various epileptic syndromes, including children.
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PMID:[Therapeutic options provided by new antiepileptic drugs]. 929 53

Six studies are cited to demonstrate that topiramate is effective as adjunctive therapy for refractory partial-onset seizures in adults. Subsequent studies indicate that topiramate is also effective as monotherapy in adults and as adjunctive therapy for partial-onset seizures in children, tonic-clonic seizures of nonfocal origin in children and adults, and drop attacks in Lennox-Gastaut syndrome. Adverse effects for adults and children included dizziness, fatigue, ataxia, confusion, somnolence, nephrolithiasis, paresthesia, and weight loss. More adverse effects were observed at higher doses. Topiramate exhibits rapid absorption, long duration of action, and minimal interaction with other antiepileptic drugs.
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PMID:Topiramate. 1053 Jun 97

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study--the open-label continuation phase of several short-term clinical trials--was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults.
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PMID:Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy. 1208 84

Rufinamide is a triazole derivative structurally unrelated to currently marketed antiepileptic drugs. Rufinamide was profiled for anticonvulsant activity at the National Institutes of Health and showed broad-spectrum anticonvulsant properties at nontoxic doses in animal models. The principal mechanism of action of rufinamide is considered to be the modulation of the activity of sodium channels and, in particular, prolongation of the inactive state of the channel. Rufinamide provides an efficacious and well-tolerated treatment option for use as adjunctive therapy in patients with partial seizures and with Lennox-Gastaut syndrome (LGS). In LGS, rufinamide is effective in controlling multiple seizure types and in reducing the severity of the seizures. The most commonly observed (> or =10%) adverse experiences seen in association with rufinamide are headache, dizziness, fatigue, somnolence and nausea. Rufinamide is generally well tolerated, and its safety profile is well-established.
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PMID:Rufinamide. 1719 32

Rufinamide (1-[2,6-difluorobenzyl]-1H-1,2,3-triazole-4-carboxamide) is a new anti-epileptic drug with a novel triazole derivative structure. The suspected mechanism of action is limitation of sodium-dependent action potentials, thought to result in a membrane stabilizing effect. Rufinamide is extensively metabolized in the liver by non-CYP450 enzymes with an elimination half-life of 8 - 12 h. Three randomized, placebo-controlled trials have shown that rufinamide is effective against partial seizures in adults. Efficacy in the Lennox-Gastaut syndrome, a severe, disabling childhood onset epilepsy syndrome, was shown in a single, randomized, placebo-controlled trial. It has recently been approved for treatment of Lennox-Gastaut syndrome in Europe. In the US it is under regulatory review. Most common adverse effects are somnolence, fatigue, dizziness, dipolopia, nausea and ataxia. Rufinamide has shown promise as adjunctive treatment for Lennox-Gastaut syndrome and may have some role in localization related epilepsies as well.
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PMID:Rufinamide: a new anti-epileptic medication. 1769 94

Rufinamide is a new antiepileptic drug that is effective in acute animal seizure models and also in the kindling model of epilepsy with a high protective index. Its mechanism of action is largely unknown; studies suggest an effect at voltage-gated sodium channels, but whether this is its main mode of action remains to be determined. Rufinamide can be administered twice daily and has minimal drug interactions (it does, however, interact with the contraceptive pill). Food markedly increases absorption, which may complicate clinical use. Trials indicate that rufinamide is effective as adjunctive therapy in partial epilepsy and the Lennox-Gastaut syndrome with minimal adverse effects including headache, dizziness and fatigue. In addition, rufinamide has a favorable cognitive side-effect profile. However, it remains uncertain whether rufinamide offers significant advantages over other current antiepileptic drugs, and the results of further clinical trials are awaited.
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PMID:Rufinamide. 1772 46

Rufinamide, a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs (AEDs), is in development for the adjunctive treatment of Lennox-Gastaut syndrome (LGS) in children and adults. Rufinamide is well absorbed after oral administration, demonstrates low protein binding, and is metabolized by enzymatic hydrolysis without involvement of cytochrome P450 enzymes, conferring a low drug interaction potential. In a randomized, double-blind trial involving 138 adult and pediatric patients with LGS, compared with placebo, rufinamide 45 mg/kg/day resulted in significantly superior reductions in drop attacks (median change -42.5% vs +1.4% with placebo) and total seizures (-32.1% vs -11.7% with placebo), accompanied by significantly higher responder rates. These results are comparable with findings reported for other AEDs in randomized, controlled clinical trials in patients with LGS. Rufinamide produced statistically significant seizure reduction which was maintained during long-term therapy and accompanied by good tolerability. The most frequently reported adverse events from a pooled safety database evaluating short- and long-term therapy were headache (22.9% and 29.5%), dizziness (15.5% and 22.5%) and fatigue (13.6% and 17.7%). Rufinamide therefore presents a favorable efficacy and tolerability profile and is a promising candidate for the adjunctive therapy of LGS.
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PMID:Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy). 1930 May 35


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