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Epilepsia na gravidez: terapêutica farmacológica na mulher e implicações no desenvolvimento fetal
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Abstract(s)
A epilepsia é uma doença neurológica crónica de natureza progressiva que surge em qualquer idade e sexo. É uma das doenças neurológicas mais comuns em todo o mundo afetando um elevado número de mulheres em idade fértil. A doença manifesta-se através da ocorrência de crises convulsivas com tendência recorrente, implicando muitas vezes o recurso a medicação crónica.
Os riscos maternos e fetais durante a gravidez na mulher epilética são relativamente superiores quando comparados com mulheres saudáveis. Este risco deve-se não só aos episódios convulsivos que podem ocorrer, mas também advém da terapia realizada pela mulher antes e durante a gestação.
A escolha do fármaco antiepilético adequado deve basear-se no histórico clínico da doente e considerar os diferentes fatores que podem influenciar o desenvolvimento fetal e a recorrência dos episódios epiléticos durante a gravidez. As alterações fisiológicas no decurso da gestação também irão apresentar implicações na cinética dos fármacos, sendo frequentemente necessário o ajuste das doses para garantir o controlo da doença e a segurança clínica. A suplementação alimentar com ácido fólico é aconselhada de modo a diminuir o risco associado à utilização dos fármacos antiepiléticos, bem como a análise cuidada das vantagens e desvantagens da realização de mono- e politerapia, uma vez que, o risco de teratogenicidade aumenta quando o regime politerapêutico é implementado.
O fármaco antiepilético considerado mais teratogénico é o ácido valpróico, devendo ser evitado na mulher grávida. As malformações congénitas major mais comuns são as cardíacas, neurológicas, fendas orais e hipospadias. Estas malformações surgem devido a mecanismos de teratogenicidade como a epoxidação e stress oxidativo provocados por fármacos antiepiléticos.
Desta forma, a presente monografia apresenta uma revisão bibliográfica acerca da classificação, diagnóstico e fisiopatologia da epilepsia e farmacoterapia da doença, com maior enfoque na mulher grávida epilética. Bem como, revisão dos mecanismos teratogénicos e malformações resultantes da exposição do feto aos fármacos antiepiléticos.
Epilepsy is a chronic neurological disease with a progressive nature that starts in any age and sex. It is one of the most common neurological diseases worldwide, affecting a large number of women in childbearing age. This disease manifests through the occurrence of epileptic seizures, with a recurrent tendency, often involving the need for chronic medication. Maternal and foetal risks during pregnancy in an epileptic woman are relatively higher when compared to healthy women. This risk is due not only to the convulsive episodes but also comes from the therapy carried out by women before and during the gestation period. The choice of the adequate antiepileptic drug should be based on the patient’s clinical history also considering the different factors that can influence the foetal development and recurrence of epileptic seizures during pregnancy. Physiological changes during pregnancy will also have implications for drug kinetics, and dose adjustments are often necessary to ensure seizure control and clinical safety. The supplementation with acid folic is recommended in order to reduce the risk associated with the pharmacotherapy with antiepileptic drugs, as well as careful analysis of the benefits and risks of mono- and polytherapy must be performed, since the teratogenic risk increases when a polytherapeutic regimen is implemented. The most teratogenic antiepileptic drug is valproic acid, and it should be avoided in the pregnant women. The most common major congenital malformations are the cardiac, neurological, oral clefts and hypospadias. These malformations emerge due to the teratogenic mechanisms like epoxidation and oxidative stress aggravated by the antiepileptic drugs. Thus, the present monograph consists of a bibliographic revision about the classification, diagnosis, and physiopathology of epilepsy as well as the pharmacotherapy of the disease, with a bigger focus on the epileptic pregnant women. In addition, a revision of the mechanisms of teratogenicity and malformations resulting from foetal exposure to the antiepileptic drug will also be addressed.
Epilepsy is a chronic neurological disease with a progressive nature that starts in any age and sex. It is one of the most common neurological diseases worldwide, affecting a large number of women in childbearing age. This disease manifests through the occurrence of epileptic seizures, with a recurrent tendency, often involving the need for chronic medication. Maternal and foetal risks during pregnancy in an epileptic woman are relatively higher when compared to healthy women. This risk is due not only to the convulsive episodes but also comes from the therapy carried out by women before and during the gestation period. The choice of the adequate antiepileptic drug should be based on the patient’s clinical history also considering the different factors that can influence the foetal development and recurrence of epileptic seizures during pregnancy. Physiological changes during pregnancy will also have implications for drug kinetics, and dose adjustments are often necessary to ensure seizure control and clinical safety. The supplementation with acid folic is recommended in order to reduce the risk associated with the pharmacotherapy with antiepileptic drugs, as well as careful analysis of the benefits and risks of mono- and polytherapy must be performed, since the teratogenic risk increases when a polytherapeutic regimen is implemented. The most teratogenic antiepileptic drug is valproic acid, and it should be avoided in the pregnant women. The most common major congenital malformations are the cardiac, neurological, oral clefts and hypospadias. These malformations emerge due to the teratogenic mechanisms like epoxidation and oxidative stress aggravated by the antiepileptic drugs. Thus, the present monograph consists of a bibliographic revision about the classification, diagnosis, and physiopathology of epilepsy as well as the pharmacotherapy of the disease, with a bigger focus on the epileptic pregnant women. In addition, a revision of the mechanisms of teratogenicity and malformations resulting from foetal exposure to the antiepileptic drug will also be addressed.
Description
Keywords
Epilepsia Fármacos antiepiléticos Gravidez Malformações fetais Teratogenicidade