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Inovações terapêuticas no âmbito da profilaxia e tratamento das crises agudas de enxaqueca
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Abstract(s)
A enxaqueca é uma doença neurovascular e multifatorial incapacitante, com uma prevalência mundial de cerca de 11,6%, afetando tanto adultos, como adolescentes e crianças. O seu impacto no quotidiano dos doentes é bastante significativo, impedindo-os por vezes de realizar as suas tarefas diárias. Desta forma, esta patologia está frequentemente associada ao absentismo laboral e escolar. Por outro lado, é também responsável por custos elevados na área da saúde.
A grande problemática em torno da enxaqueca prende-se não só com a desvalorização desta doença por parte de alguns profissionais de saúde, mas também com a falta de eficácia e segurança das terapêuticas atualmente instituídas para a sua profilaxia e tratamento sintomático. As terapêuticas convencionais são, na sua maioria, inespecíficas e acarretam um número elevado de contraindicações e efeitos adversos, o que dificulta a escolha de um regime terapêutico adequado e, como consequência, conduz ao abandono da terapêutica. Por outro lado, algumas opções terapêuticas, nomeadamente os triptanos, podem ainda conduzir a um quadro crónico e refratário, se utilizadas de forma regular e prolongada.
As limitações das terapêuticas atualmente instituídas prendem-se, sobretudo, com o desconhecimento dos mecanismos fisiopatológicos da enxaqueca. Nos dias de hoje, assume-se que as crises de enxaqueca resultam da ativação do sistema trigémino-vascular, que desencadeia um processo de inflamação neurogénica, com consequente libertação de substâncias vasoativas, como por exemplo, a calcitonin gene-related peptide (CGRP). Porém, o evento que está na origem da ativação do sistema trigémino-vascular permanece desconhecido.
O papel destas substâncias vasoativas tem vindo a ser estudado, o que possibilita a identificação de novos alvos terapêuticos, permitindo assim o desenvolvimento de novas opções terapêuticas mais especificas, mais toleráveis e mais seguras. A nível não farmacológico, destaca-se a neuromodulação, com a promessa de diminuir a excitabilidade neuronal, com o menor número de efeitos adversos e interações medicamentosas; a nível farmacológico, destacam-se os fármacos que antagonizam a ação das substâncias vasoativas envolvidas na fisiopatologia da enxaqueca, como por exemplo, os gepants e os anticorpos monoclonais anti-CGRP e anti-recetor da CGRP. Neste contexto, a presente monografia pretende explorar as mais recentes e promissoras inovações terapêuticas no âmbito da enxaqueca, desenvolvidas com base nas últimas descobertas acerca da fisiopatologia desta doença, através de uma revisão bibliográfica.
Migraine is a disabling neurovascular and multifactorial disease, with a global prevalence of about 11,6%, affecting not only adults, but also adolescents and children. Its impact in patient’s everyday life is quite significant, preventing them to realize their daily activities. Thus, migraine is often associated with laboral and scholar absenteeism. Moreover, it is also responsible for high health costs. The big problematical question involving migraine is not only related to its health providers’ undervaluation, but also to the lack of efficacy and safety of the medicines approved for its prophylaxis and acute treatment. The conventional therapeutics are mostly unspecific and possess a high number of contraindications and adverse effects, which difficults the establishment of an adequate therapy and diminishes the therapeutic compliance. On the other hand, some of these therapeutic options, such as triptans, may lead to a refractary and chronic migraine, if regularly used. The limitations of the medicines used in prevention and abortive therapies of migraine is especially due to the misunderstanding of the pathophysiological mechanism of migraine. Nowadays, it is thought that the migraine crises result from the trigeminovascular system activation, which leads to neurogenic inflammation, being responsible for the release of vasoactive substances, like the calcitonin gene-related peptide (CGRP). However, the event in the origin of the activation of the trigeminovascular system is still unknown. The importance of these vasoactive substances is being studied, which enables the identification of new therapeutic targets, which in turn allows the development of new therapeutic options more specific, more tolerable and safer. Non-pharmacologically, the neuromodulation stands out, with the promise of decreasing the neuronal excitability, with the smallest number of adverse effects and drug interactions; in a pharmacological manner, it should be considered the molecules that antagonize the action of the vasoactive substances evolved in the pathophysiology of migraine, such as the gepants and the anti-CGRP receptor and anti-CGRP monoclonal antibodies. In this context, the present monography pretends to review and explore the most recent and promising emerging therapies to prevent or treat migraines, which are still in development thanks to the latest discoveries on the pathophysiology of migraine, through a bibliographic review.
Migraine is a disabling neurovascular and multifactorial disease, with a global prevalence of about 11,6%, affecting not only adults, but also adolescents and children. Its impact in patient’s everyday life is quite significant, preventing them to realize their daily activities. Thus, migraine is often associated with laboral and scholar absenteeism. Moreover, it is also responsible for high health costs. The big problematical question involving migraine is not only related to its health providers’ undervaluation, but also to the lack of efficacy and safety of the medicines approved for its prophylaxis and acute treatment. The conventional therapeutics are mostly unspecific and possess a high number of contraindications and adverse effects, which difficults the establishment of an adequate therapy and diminishes the therapeutic compliance. On the other hand, some of these therapeutic options, such as triptans, may lead to a refractary and chronic migraine, if regularly used. The limitations of the medicines used in prevention and abortive therapies of migraine is especially due to the misunderstanding of the pathophysiological mechanism of migraine. Nowadays, it is thought that the migraine crises result from the trigeminovascular system activation, which leads to neurogenic inflammation, being responsible for the release of vasoactive substances, like the calcitonin gene-related peptide (CGRP). However, the event in the origin of the activation of the trigeminovascular system is still unknown. The importance of these vasoactive substances is being studied, which enables the identification of new therapeutic targets, which in turn allows the development of new therapeutic options more specific, more tolerable and safer. Non-pharmacologically, the neuromodulation stands out, with the promise of decreasing the neuronal excitability, with the smallest number of adverse effects and drug interactions; in a pharmacological manner, it should be considered the molecules that antagonize the action of the vasoactive substances evolved in the pathophysiology of migraine, such as the gepants and the anti-CGRP receptor and anti-CGRP monoclonal antibodies. In this context, the present monography pretends to review and explore the most recent and promising emerging therapies to prevent or treat migraines, which are still in development thanks to the latest discoveries on the pathophysiology of migraine, through a bibliographic review.
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Keywords
Enxaqueca Inovações terapêuticas Profilaxia Terapêutica Fisiopatologia