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Lamotrigina, da farmacocinética à farmacodinâmica
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| PPG_12392 | 1.06 MB | Adobe PDF |
Advisor(s)
Abstract(s)
A epilepsia é uma doença caracterizada por crises espontâneas que podem ser convulsivas ou não, originadas por descargas anormais, excessivas e hipersincrónicas dos neurónios. Mais de 80% dos indivíduos com epilepsia vivem em países subdesenvolvidos, onde 60 a 90% dos pacientes permanece sem tratamento devido às deficiências do sistema de saúde interno e ao estigma social presente.
Existem diversas hipóteses explicativas para a causa da epilepsia. A classificação das crises epilépticas está dividida em dois grupos principais, segundo o mecanismo biológico específico envolvido nas convulsões e de acordo com a sua localização anatómica, bem como em três subgrupos: as crises isoladas ou autolimitadas; as contínuas configurando status epilepticus e os fatores precipitantes envolvidos nas crises reflexas, que podem desencadear crises focais ou generalizadas.
O tratamento farmacológico passa pela utilização da Lamotrigina (LTG), antiepiléptico com eficácia no controlo de crises parciais, com ou sem generalização secundária, de crises tónico-clónicas primariamente generalizadas, de ausências e de crises atónicas.
A elevada biodisponibilidade, baixa ligação às proteínas plasmáticas, eficiente penetração da barreira hematoencefálica, tempo de semi-vida compatível com a administração de uma ou duas doses diária, cinética de eliminação linear, biotransformação pouco extensa e ausência de fenómenos de autoindução, demonstram o perfil cinético favorável da LTG.
O principal mecanismo de ação da LTG é a inibição da libertação de glutamato, prolongando o seu estado de inativação, estabilizando a membrana pré-sináptica, prevenindo assim a libertação excessiva dos aminoácidos excitatórios.
Apesar dos estudos clínico evidenciarem que a LTG é bem tolerada pela maioria dos pacientes, ainda existem constrangimentos no estabelecimento de uma relação bem definida entre os níveis plasmáticos obtidos e a resposta farmacológica desencadeada.
The epilepsy is a disease characterized by spontaneous seizures that may be convulsive or not, caused by abnormal, excessive and hypersynchronous discharges from the neurons. More than 80% of individuals with epilepsy live in underdeveloped countries, where 60-90% of patients remain untreated due to deficiencies of the internal health system and the social stigma present. There are several explanatory hypotheses for the cause of epilepsy. Epileptic seizures can be divided into two main groups, according to the specific biological mechanisms involved in the seizures and according to their anatomical location, or can be divided in following three subgroups: isolated or self-limited seizures; the continuous configuring status epilepticus and the precipitating factors involved in reflex crises, which can trigger focal or generalized seizures. Pharmacological treatment involves the use of Lamotrigine, an antiepileptic drug that is effective in controlling partial seizures, with or without secondary generalization, of primarily generalized tonic-clonic seizures, absences and atonic seizures. It’s high bioavailability, low plasma protein binding, efficient penetration of the blood-brain barrier, half-life time compatible with one or two daily doses, linear elimination kinetics, non extensive biotransformation, and absence of autoinduction, demonstrates the favourable kinetic profile of Lamotrigine. The main mechanism of action of Lamotrigine is the inhibition of glutamate release, prolonging its inactivation state, stabilizing the presynaptic membrane, thus preventing the excessive release of excitatory amino acids. Although clinical studies have shown that lamotrigine is well tolerated by most patients, there are still constraints in establishing a well-defined relationship between the plasma levels obtained and the pharmacological response triggered.
The epilepsy is a disease characterized by spontaneous seizures that may be convulsive or not, caused by abnormal, excessive and hypersynchronous discharges from the neurons. More than 80% of individuals with epilepsy live in underdeveloped countries, where 60-90% of patients remain untreated due to deficiencies of the internal health system and the social stigma present. There are several explanatory hypotheses for the cause of epilepsy. Epileptic seizures can be divided into two main groups, according to the specific biological mechanisms involved in the seizures and according to their anatomical location, or can be divided in following three subgroups: isolated or self-limited seizures; the continuous configuring status epilepticus and the precipitating factors involved in reflex crises, which can trigger focal or generalized seizures. Pharmacological treatment involves the use of Lamotrigine, an antiepileptic drug that is effective in controlling partial seizures, with or without secondary generalization, of primarily generalized tonic-clonic seizures, absences and atonic seizures. It’s high bioavailability, low plasma protein binding, efficient penetration of the blood-brain barrier, half-life time compatible with one or two daily doses, linear elimination kinetics, non extensive biotransformation, and absence of autoinduction, demonstrates the favourable kinetic profile of Lamotrigine. The main mechanism of action of Lamotrigine is the inhibition of glutamate release, prolonging its inactivation state, stabilizing the presynaptic membrane, thus preventing the excessive release of excitatory amino acids. Although clinical studies have shown that lamotrigine is well tolerated by most patients, there are still constraints in establishing a well-defined relationship between the plasma levels obtained and the pharmacological response triggered.
Description
Keywords
Lamotrigina Epilepsia Farmacocinética Farmacodinâmica Lamotrigine Epilepsy Pharmacokinetics Pharmacodynamics