Neurologia: Fisiopatologia e farmacoterapia de doenças do sistema nervoso central

Epilepsia Paroxismo de disfunção cerebral devido a descarga anormal, excessiva de neurónios do SNC.

Crise epiléptica

5-10% da população Epilepsia

Síndroma polimórfico polimórfico de distúrbio da actividade actividade eléctrica do SNC causado por perturbação neurológica crónica subjacente. Recorrência periódica de crises epilépticas epilépticas com ou sem convulsão. 1% da população Crises epilépticas

Parciais ou focais

Generalizadas

⅓

< 1 crise/ano

⅓

1-12 crises/ano

⅓

> 1 crise/mês

70% remissão 30% epilepsia crónica



Simples



Ausências



Complexas



Tónico-clónicas



Com generalização secundária



Tónicas

60% causa desconhecida



Atónicas

15% doença vascular (49% idoso)



Mioclónicas

6% tumor (11% idoso)

⅔

⅓

60% crises convulsivas convulsivas

FISIOPATOLOGIA E FARMACOTERAPIA FARMACOTERAPIA I – 2007/2008

nº de crises crises nos 6 meses meses após 1ª 1ª

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Epilepsia

Inibição

Excitação SNC

O cérebro normal pode sofrer uma crise epiléptica. A sensibilidade e o limiar variam com o indivíduo. Ex: convulsões febris. 

Algumas situações representam uma elevada probabilidade probabilidade de desencadearem desencadearem uma crise epiléptica. Factores epileptogénicos: traumatismo craniano severo penetrante (50% risco), AVC, infecções… 



As crises epilépticas epilépticas são episódicas. Factores precipitantes.

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Epilepsia Factores Facto res epileptog epileptogénic énicos os / precipitant precipitantes es Traumatismo craniano Hiperventilação Estímulos sensitivos Sono ou privação de sono

Stresse AVC Flutuações hormonais

Fármacos

Doença neurodegenerativa neurodegenerativa Álcool Drogas de abuso

Infecções SNC Factores perinatais

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Epilepsia Fármacos que podem causar crises epilépticas Antimicro Antimicrobiano bianoss / antivirai antiviraiss

Anestésicos e analgésicos

Drogas de abuso

β-lactâmicos

Meperidina

Anfetamina

Quinolonas

Tramadol

Cocaína

Aciclovir

Anestésicos locais

Isoniazida Ganciclovir

Imunomoduladores

Psicotrópicos

Abstinência de sedativos-hipnóticos sedativos-hipnóticos

Ciclosporina

Antidepressores

Álcool

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Epilepsia Mecanismos de iniciação e propagação das crises parciais 

Potenciais de acção de elevada frequência fr equência 





Despolarização Despolarização prolongada por influxo inf luxo de Ca 2+ → abertura de canais de Na+ dependentes do potencial → influxo de Na+ Hiperpol Hiperpolariza arização ção pós-poten pós-potencial cial mediada mediada por receptore receptoress GABAérgicos GABAérgicos ou canais de K+

Hipersincronização

1. ↑ K+ extracelular 2. Acumulação de Ca 2+ nos terminais préjuncionais préjuncionais

Factores intrínsecos 

neurotransmissores



moduladores de receptores



astrócitos, oligodendrócitos… oligodendrócitos…

Excitabilidade neuronial

3. Activação de receptores NMDA Factores extrínsecos

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Epilepsia Crise epiléptica 

O clínico raramente presencia uma crise epiléptica



É funda fundamen mental tal a educação do doente, familiares e outras pessoas relacionadas com o doente



Qualquer pessoa deve estar atenta a alguns aspectos relevantes: 

Algum factor precipitou a crise?



Quanto durou a crise?



Qual o comportamento do doente antes da crise? (alguma (alguma queixa queixa?? - aura)



Houve movimentos anormais dos olhos?



A convulsão foi localizada ou envolveu o corpo todo?



Verificou-se perda de consciência consciência??



Observou-se incontinência urinária?



Qual o comportamen comportamento to do doente depois da crise? (confusão, amnésia, …)

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Doença de Parkinson Doença neurodegenerat neurodegenerativa iva resultante da morte morte de de neurónios  neurónios  dopaminérg dopam inérgicos icos da substânc substância ia nigra. nigra.

Parkinsoninsmo

75% Doença de Parkinson idiopática

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Doença de Parkinson Sintomas não-motores: sonhos vividos e alucinações, apneia)  Alterações sensitivas (“intranquilidade (“intranquilidade interior”/“acatísia”) e dor (nas extremidades; extremidades; sintoma ou “wearing “wearing off”) 

Perturbações do sono (sonolência diurna e desordens nocturnas,

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Doença de Parkinson 

Deficiência no complexo 1 mitocondrial



Lesão por radiac radiacais ais livres livres e stresse stresse oxidativ oxidativoo



Disfunção proteossómica



Apoptose

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Demência Patologia Doença Doença de Alzhe Alzheime imerr

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Epilepsia Tratamento farmacológic farmacológico o Objectivo geral: Mecanismo de acção



Diminuir o risco de morte



Melhorar a qualidade de vida

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