Fármacos antiepiléticos: papel dos polimorfismos genéticos na resposta à terapêutica
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2018
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A epilepsia é uma das doenças neurológicas mais comuns no mundo, afetando cerca de 50 milhões de pessoas. Esta doença caracteriza-se pela existência de uma predisposição permanente para a ocorrência de crises epiléticas, que deriva de um processo de epileptogénese que ocorre no cérebro, a partir de diferentes mecanismos.
O tratamento da epilepsia é feito com recurso a fármacos antiepiléticos com ação anticonvulsivante, que atuam no controlo sintomático da doença. Cerca de um terço dos doentes continua a sofrer de crises, apesar da toma correta dos fármacos, sendo as causas da farmacorresistência ainda desconhecidas, pensando-se que possam estar associadas a fatores genéticos. Um grande número de doentes desenvolve reações adversas, entre as quais a síndrome de Stevens-Johnson e a necrólise epidérmica tóxica, que apesar de pouco frequentes conduzem a uma taxa de mortalidade elevada.
De modo a melhorar a resposta à terapêutica pretende-se implementar os princípios da medicina de precisão na prática clínica, isto é, escolher o tratamento mais adequado aos doentes, com base nas suas características individuais. Assim, têm sido realizados vários estudos na área da Farmacogenómica, na tentativa de identificar polimorfismos genéticos associados à redução da eficácia dos fármacos e ao aumento da suscetibilidade a reações adversas. Um desses exemplos é a recomendação para a identificação do alelo HLA-B*1502, em indivíduos de descendência asiática, devido ao elevado risco de desenvolvimento de reações adversas cutâneas graves.
Epilepsy is one of the most common neurological diseases worldwide, affecting about 50 million people. This disease is characterized by the existence of a permanent predisposition for the occurrence of epileptic seizures, which derives from an epileptogenesis process that occurs in the brain, as a result of different mechanisms. The treatment of epilepsy is performed with antiepileptic drugs with anticonvulsive action, which act in the symptomatic control of the disease. About one third of patients continue to experience seizures, despite the correct intake of drugs and, the causes of drug resistance are still unknown, are thought to be associated with genetic factors. A large number of patients develop adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, which, although uncommon, lead to a high mortality rate. In order to improve the response to therapy, it is intended to implement the principles of precision medicine in clinical practice, that is, to choose the most appropriate treatment for patients based on their individual characteristics. Therefore, several studies have been carried out in the field of Pharmacogenomics, in an attempt to identify genetic polymorphisms associated with the reduction of drug efficacy and the increased susceptibility to adverse reactions. One such example is the recommendation for the identification of the HLA-B*1502 allele in people with Asian ancestry, due to the high risk of developing severe cutaneous adverse reactions.
Epilepsy is one of the most common neurological diseases worldwide, affecting about 50 million people. This disease is characterized by the existence of a permanent predisposition for the occurrence of epileptic seizures, which derives from an epileptogenesis process that occurs in the brain, as a result of different mechanisms. The treatment of epilepsy is performed with antiepileptic drugs with anticonvulsive action, which act in the symptomatic control of the disease. About one third of patients continue to experience seizures, despite the correct intake of drugs and, the causes of drug resistance are still unknown, are thought to be associated with genetic factors. A large number of patients develop adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, which, although uncommon, lead to a high mortality rate. In order to improve the response to therapy, it is intended to implement the principles of precision medicine in clinical practice, that is, to choose the most appropriate treatment for patients based on their individual characteristics. Therefore, several studies have been carried out in the field of Pharmacogenomics, in an attempt to identify genetic polymorphisms associated with the reduction of drug efficacy and the increased susceptibility to adverse reactions. One such example is the recommendation for the identification of the HLA-B*1502 allele in people with Asian ancestry, due to the high risk of developing severe cutaneous adverse reactions.
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Orientação: João Guilherme Costa
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MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS, CIÊNCIAS FARMACÊUTICAS, EPILEPSIA, POLIMORFISMO GENÉTICO, FARMACOGENÓMICA, PHARMACEUTICAL SCIENCES, EPILEPSY, GENETIC POLYMORPHISM, PHARMACOGENOMICS, MEDICINA DE PRECISÃO, PRECISION MEDICINE