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      Antiepilépticos de tercera generación Translated title: Third generation antiepilectics

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          Abstract

          Existen numerosos fármacos antiepilépticos de primera y segunda generación, disponibles hoy en el mercado internacional y en Cuba. Sin embargo, no todos resultan satisfactorios para el control de las crisis, debido a dificultades de tolerancia y toxicidad, y a sus propiedades farmacocinéticas. Se ofrece una revisión sobre los principales medicamentos antiepilépticos de tercera generación que en años recientes han sido investigados, para aumentar su eficacia y minimizar sus efectos colaterales, e introducidos en el arsenal terapéutico. Algunos fármacos continúan sometidos a ensayos experimentales y clínicos.

          Translated abstract

          There are many first and second generation antiepilectic drugs available in the international marked and also in Cuba. However, not all are satisfactory for the crisis control due to difficulties of tolerance and toxicity, and to its pharmacokinetic properties. Authors offer a review on the main three generation antiepilectic drugs that in past years have been researched to increase its effectiveness and to minimize its side effects, and entered in the therapeutical array. Some drugs underwent clinical and experimental trials.

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          Most cited references48

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          Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome.

          Lennox-Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment-resistant seizures and high rates of seizure-related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities. We conducted a double-blind, randomized, placebo-controlled trial of the antiepileptic drug rufinamide in patients with Lennox-Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic-atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike-and-wave pattern on EEG. After a 28-day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference (p or=10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%). Rufinamide was an effective and well-tolerated treatment for seizures associated with Lennox-Gastaut syndrome.
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            Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial.

            To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. This multicenter, double-blind, placebo-controlled trial randomized patients (age 16-70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period. Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose-related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed. Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial-onset seizures in patients with epilepsy.
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              Neurosteroid access to the GABAA receptor.

              GABAA receptors are a pivotal inhibitory influence in the nervous system, and modulators of the GABAA receptor are important anesthetics, sedatives, anticonvulsants, and anxiolytics. Current views of receptor modulation suggest that many exogenous drugs access and bind to an extracellular receptor domain. Using novel synthetic steroid analogs, we examined the access route for neuroactive steroids, potent GABAA receptor modulators also produced endogenously. Tight-seal recordings, in which direct aqueous drug access to receptor was prevented, demonstrated that steroids can reach the receptor either through plasma membrane lateral diffusion or through intracellular routes. A fluorescent neuroactive steroid accumulated intracellularly, but recordings from excised patches indicated that the intracellular reservoir is not necessary for receptor modulation, although it can apparently equilibrate with the plasma membrane within seconds. A membrane impermeant neuroactive steroid modulated receptor activity only when applied to the inner membrane leaflet, demonstrating that the steroid does not access an extracellular modulatory site. Thus, neuroactive steroids do not require direct aqueous access to the receptor, and membrane accumulation is required for receptor modulation.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                ped
                Revista Cubana de Pediatría
                Rev Cubana Pediatr
                Editorial Ciencias Médicas (Ciudad de la Habana )
                1561-3119
                March 2010
                : 82
                : 1
                : 0
                Affiliations
                [1 ] Hospital Pediátrico William Soler Cuba
                Article
                S0034-75312010000100010
                9503dbbb-f903-464e-9a3e-dcec248a9739

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Cuba

                Self URI (journal page): http://scielo.sld.cu/scielo.php?script=sci_serial&pid=0034-7531&lng=en
                Categories
                PEDIATRICS

                Pediatrics
                Third generation antiepilectics,refractory epilepsy,antiepilectic effectiveness,Antiepilépticos de tercera generación,epilepsia refractaria,eficacia antiepiléptica

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