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Novas abordagens farmacológicas no tratamento de doentes com diagnóstico de AVC isquémico com contraindicação para terapêutica trombolítica
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O AVC isquémico é umas das principais causas de morte no mundo, estando inserido nas doenças cardiovasculares. O AVC isquémico agudo é a maior causa de mortalidade e incapacidade dos adultos e a sua importância tendencialmente será maior à medida que a população envelhece. Caracteriza-se pela perda de circulação sanguínea em determinada área do cérebro, levando a perda de função neurológica na zona correspondente. Atualmente a única terapêutica aprovada é a trombólise, nomeadamente a administração de alteplase (rt-PA), num intervalo até 3 horas após o início dos sintomas. No entanto, o número de doentes elegíveis para este tratamento é diminuto, tendo em conta as várias contraindicações existentes. Nesta monografia será abordada a investigação em torno da procura de novas abordagens farmacológicas para o tratamento de doentes com diagnóstico de AVC isquémico, para os quais está contraindicada a terapêutica preconizada. Devido à complexidade da fisiopatologia desta doença têm sido propostos vários alvos terapêuticos, em que a inflamação surge como o principal alvo. Têm sido analisadas várias possibilidades de atuação, sendo que a área do repurposing aparenta ser mais promissora. Fármacos como a minociclina, fingolimod, candesartan entre outros demonstraram ação neuroprotetora, tornando-se potenciais fármacos para esta patologia. As terapias baseadas em células estaminais têm emergido como nova direção no tratamento protetor e regenerativo do AVC isquémico. Importa avaliar os modelos animais atualmente utilizados, visto que ainda há um longo caminho a percorrer dado que a transposição da investigação pré-clínica para clínica tem sido alvo de inúmeros insucessos e nenhum fármaco demonstrou capacidade similar à terapêutica trombolítica. De futuro, fármacos como as Estatinas, ARAs, minociclina e fatores de crescimento, como a eritropoietina podem ser utilizados na prática clínica. Para além disso, o futuro do tratamento desta doença recai, mais provavelmente, em terapia combinada do que em monoterapia. A combinação de terapias e os esforços realizados para alargar a janela terapêutica da trombólise poderá acarretar mais benefícios em doentes que sofreram AVC isquémico agudo.
Ischemic stroke, a cardiovascular disease, is one of the leading causes of death in the world. The acute ischemic stroke is the major cause of disability in adults and its relevance will be increasingly bigger as the population ages. This disease is decribed as a loss of blood flow in a certain brain área, leading to loss of neurological function in said zone. Currently, the only approved drug is alteplase, a trombolytic therapy, and must be given in the first three hours after onset of symptoms. However, the number of elegible patients is quite short given its strict criteria of eligibility. In this document it will be made an approach to current research regarding new pharmacological strategies for the treatment of ischemic stroke, for patients where it isn’t possible to give thrombolysis. Due to the complexity of stroke pathophysiology, it has been proposed several therapeutic targets, in which inflammation as emerged as main target. The most promissing approach seems to be repurposing of drugs. Drugs such as minocline, fingolimod, candesartan amongst others have demonstrated neuroprotective action, making the possible drugs for the treatment. Stem cells based therapy as emerged as a new direction for the protective and regenerative treatment of ischemic stroke. It is important to evaluate the currently used animal models, considering that there is a long way to go, specially regarding translation of preclinic to clinic research, which has been suffering several failures and nothing seems to be as effective as alteplase. In the future, drugs such as statins, minocline, growth factos such as erythropoietin can be used in the clinical practice. Clearly, the future of the treatment of ischemic stroke is in combined therapy rather than monotherapy. The combination of therapies and the efforts to broad the therapeutical time window for thrombolysis will bring more benefits to patients who have sufferend acute ischemic stroke.
Ischemic stroke, a cardiovascular disease, is one of the leading causes of death in the world. The acute ischemic stroke is the major cause of disability in adults and its relevance will be increasingly bigger as the population ages. This disease is decribed as a loss of blood flow in a certain brain área, leading to loss of neurological function in said zone. Currently, the only approved drug is alteplase, a trombolytic therapy, and must be given in the first three hours after onset of symptoms. However, the number of elegible patients is quite short given its strict criteria of eligibility. In this document it will be made an approach to current research regarding new pharmacological strategies for the treatment of ischemic stroke, for patients where it isn’t possible to give thrombolysis. Due to the complexity of stroke pathophysiology, it has been proposed several therapeutic targets, in which inflammation as emerged as main target. The most promissing approach seems to be repurposing of drugs. Drugs such as minocline, fingolimod, candesartan amongst others have demonstrated neuroprotective action, making the possible drugs for the treatment. Stem cells based therapy as emerged as a new direction for the protective and regenerative treatment of ischemic stroke. It is important to evaluate the currently used animal models, considering that there is a long way to go, specially regarding translation of preclinic to clinic research, which has been suffering several failures and nothing seems to be as effective as alteplase. In the future, drugs such as statins, minocline, growth factos such as erythropoietin can be used in the clinical practice. Clearly, the future of the treatment of ischemic stroke is in combined therapy rather than monotherapy. The combination of therapies and the efforts to broad the therapeutical time window for thrombolysis will bring more benefits to patients who have sufferend acute ischemic stroke.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
AVC isquémico Neuroprotecção Alteplase Reposicionamento de fármacos Mestrado Integrado - 2019