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Doença de Wilson: abordagem terapêutica
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O cobre é um oligoelemento indispensável a todos os organismos para a sua sobrevivência e desenvolvimento. Funciona como cofator de algumas enzimas que estão envolvidas em processos fisiológicos importantes, como a respiração celular, a produção de energia, a manutenção do tecido conjuntivo e a neurotransmissão. Deste modo, é fundamental garantir o seu equilíbrio homeostático. Este metal é obtido maioritariamente através da dieta alimentar. A quantidade de cobre necessária ao organismo depende da faixa etária. Desequilíbrios na quantidade ingerida podem originar um défice no organismo ou um estado de toxicidade.
Algumas doenças, como a Doença de Wilson, estão associadas a mutações genéticas que al-teram o metabolismo do cobre, e que levam à sua acumulação nos tecidos. Esta doença carac-teriza-se por uma mutação rara no gene ATP7B, que origina uma diminuição da incorporação de cobre na ceruloplasmina. As principais manifestações clínicas da doença são a presença de distúrbios neuropsiquiátricos e a doença hepática (na fase aguda ou crónica). Os anéis de Kayser-Fleischer, apesar de não serem específicos da doença, são a manifestação mais notória. A Doença de Wilson quando não tratada é fatal. O curso da doença é favorável, desde que diagnosticada o mais precoce possível. A presença de anéis de Kayser-Fleischer e de um nível de ceruloplasmina sérica baixo ( < 0,1 g/L) é geralmente suficiente para se estabelecer um diagnóstico. O tratamento deve ser introduzido logo que diagnosticada a doença. Os agentes quelantes têm sido o tratamento de eleição, pois complexam o cobre, possibilitando a sua eliminação. A D-Penicilamina foi o primeiro fármaco a ser utilizado para a Doença de Wilson. Tem vindo a ser substituído pela Trientina, dada a elevada incidência de neurotoxicidade resultante do tratamento. O Zinco diminui a absorção de cobre, e pode ser utilizado isoladamente ou associado a um agente quelante, preferencialmente em doentes com manifestações neurológicas. Estes fármacos podem ser utilizados durante o período de gestação. O Tetratiomolibdato de Amónio, apesar de não estar aprovado pela “US Food and Drug Administration”, tem demonstrado vantagens comparativamente aos agentes quelantes. Nos casos de Insuficiência Hepática Aguda, é necessária a realização do transplante hepático, pois o tratamento com agentes quelantes é geralmente ineficaz.
Copper is a trace element essential to all organisms to their survival and development. Acts as a cofactor of some enzymes that are involved in important physiological processes such as cellular respiration, energy production, the maintenance of connective tissue and neurotransmission. In this way, it is essential to ensure its homeostatic balance. This metal is obtained mostly through diet. The amount of copper required depends on the age group. Imbalances in the amount ingested can cause a deficit in the body or a state of toxicity. Some diseases such as Wilson's disease, are associated with genetic mutations that change the metabolism of copper, and lead to its accumulation in tissues. This disease is characterised by a rare mutation in the ATP7B gene, which causes a decrease in copper incorporation into ceruloplasmin. The main clinical manifestations of the disease are the presence of neuropsychiatric disorders and liver disease (acute or chronic phase). The Kayser-Fleischer rings, although not specific to the disease, are the most notorious manifestation. Wilson's disease when untreated is fatal. The course of the disease is favorable, provided it is diagnosed as early as possible. The presence of Kayser-Fleischer rings and a low level of serum ceruloplasmin ( < 0.1 g/L) is usually enough to establish a diagnosis. Treatment should be introduced as soon as the disease is diagnosed. Chelating agents have been the treatment of choice, because they complex copper, enabling its elimination. D-Penicillamine was the first drug to be used for Wilson's disease. It has been replaced by Trientine, given the high incidence of neurotoxicity resulting from the treatment. Zinc reduces copper absorption, and may be used alone or in combination with a chelating agent, preferably in patients with neurologic manifestations. These drugs can be used during the gestation period. Ammonium Tetrathiomolybdate, despite not being approved by the US Food and Drug Administration, has shown advantages over chelating agents. In cases of acute liver failure, hepatic transplantation is necessary, since treatment with chelating agents is usually ineffective.
Copper is a trace element essential to all organisms to their survival and development. Acts as a cofactor of some enzymes that are involved in important physiological processes such as cellular respiration, energy production, the maintenance of connective tissue and neurotransmission. In this way, it is essential to ensure its homeostatic balance. This metal is obtained mostly through diet. The amount of copper required depends on the age group. Imbalances in the amount ingested can cause a deficit in the body or a state of toxicity. Some diseases such as Wilson's disease, are associated with genetic mutations that change the metabolism of copper, and lead to its accumulation in tissues. This disease is characterised by a rare mutation in the ATP7B gene, which causes a decrease in copper incorporation into ceruloplasmin. The main clinical manifestations of the disease are the presence of neuropsychiatric disorders and liver disease (acute or chronic phase). The Kayser-Fleischer rings, although not specific to the disease, are the most notorious manifestation. Wilson's disease when untreated is fatal. The course of the disease is favorable, provided it is diagnosed as early as possible. The presence of Kayser-Fleischer rings and a low level of serum ceruloplasmin ( < 0.1 g/L) is usually enough to establish a diagnosis. Treatment should be introduced as soon as the disease is diagnosed. Chelating agents have been the treatment of choice, because they complex copper, enabling its elimination. D-Penicillamine was the first drug to be used for Wilson's disease. It has been replaced by Trientine, given the high incidence of neurotoxicity resulting from the treatment. Zinc reduces copper absorption, and may be used alone or in combination with a chelating agent, preferably in patients with neurologic manifestations. These drugs can be used during the gestation period. Ammonium Tetrathiomolybdate, despite not being approved by the US Food and Drug Administration, has shown advantages over chelating agents. In cases of acute liver failure, hepatic transplantation is necessary, since treatment with chelating agents is usually ineffective.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Palavras-chave
Cobre Doença de Wilson Abordagem terapêutica Mestrado Integrado - 2017