segunda-feira, 11 de agosto de 2014

Anti-hipertensivos - Classe dos diuréticos


Relembrando
Diuréticos

Conceito: São substâncias que aumentam a velocidade de formação da urina. Aumentam a excreção de eletrólitos (especialmente íons sódio e cloreto) e água, a partir do corpo. Com isto, diminuem o volume dos fluidos corporais. Usados no tratamento de condições edematosas (ex: insuficiência cardíaca congestiva, síndrome nefrótica, doenças do fígado crônicas) e controle da hipertensão. Também: hipercalcemia (excesso de cálcio), diabetes insipidus, hiperaldosteronismo primário e glaucoma.
Alvo dos diuréticos: rim (É composto néfrons, que são as unidades funcionais do rim ~ 1 milhão em cada rim)

Entendendo a fisiologia renal





Função dos rins

Excreção de produtos de degradação (uréia, ácido úrico, creatinina)
Balanço hidro-eletrolítico
Equilíbrio ácido-base
Regulação da pressão arterial


Excreção de metabólitos e substâncias estranhas




Glomérulo: filtração do sangue.
Aproximadamente 1200 mL de sangue passam por minuto através dos dois rins e chega ao néfron pelas arteríolas aferentes (CHEGADA). Cerca de 20% do sangue que chega ao glomérulo é filtrado para a cápsula de Bowman. A velocidade de filtração glomerular é de 125 mL/minuto).

Túbulo contorcido proximal: reabsorção de glicose, fosfato, sódio, bicarbonato, aminoácidos, água, etc. Ocorre a formação de bicarbonato pela enzima anidrase carbônica (presente nas células tubulares proximais):


Alça de Henle: reabsorção principalmente de água (parte descendente), e no final (parte ascendente), sódio, potássio e cloreto (sistema co-transportador Na+/K+/2 Cl-).

Túbulo contorcido distal: ação de hormônios (aldosterona), levando a retenção de sódio, cloreto e água e aumenta a excreção de potássio e H+.



No final, são excretados cerca de 2% do filtrado glomerular (urina).


CLASSE DE DIURÉTICOS


Os diuréticos exercem ação anti-hipertensiva mediante diminuição da volemia (diminuição do volume sanguíneo). Promovem a excreção de sódio e potássio, diminuindo assim a osmolaridade plasmática com consequente diminuição do volume plasmático. Os diuréticos podem ser classificados de acordo com os efeitos predominantes em diferentes pontos do néfron. Cada categoria, em função de intensidade de efeito diurético e das propriedades farmacocinéticas, é usada preferencialmente em determinadas patologias. Os diuréticos de alça, tiazídicos e poupadores de potássio são utilizados no tratamento da hipertensão.


Diuréticos osmóticos (Manitol (I.V.), uréia (I.V.), glicerina (V.O.), isossorbida (V.O.) – São fármacos relativamente inertes).  
Criam pressão osmótica, formando um complexo com a água e impedem sua reabsorção no interior do túbulo.

Diuréticos inibidores da anidrase carbônica (túbulo contornado proximal): acetalozamida, diclorfenamida, metazolamida e brinzolamida. São usados no tratamento de glaucoma e não mais como diuréticos.

Diuréticos de alça (alça ascendente de Henle): furosemida, bumetanida, ácido etacrínico, torasemida, piretanida.
São os mais utilizados e os mais potentes.
Atuam ao inibir o co-transportador Na+/K+/2Cl- na alça ascendente espessa, resultando em aumento acentuado da excreção de sódio e cloro, indiretamente de Ca e Mg e com a queda de concentração de solutos no interstício medular diminui a reabsorção de água no túbulo coletor, aumentando a sua eliminação. A eliminação de sódio e água aumenta a eliminação de K+ e H+, processo acelerado pela aldosterona. 
Interação medicamentosa:
• Digitálicos aumenta arritmias
• Probenicida e AINES: diminui resposta diurética
• Tiazídicos: sinergismo
• Altera ligações às proteínas plasmáticas

Diuréticos Tiazídicos (porção proximal do túbulo distal): os mais empregados são a Hidroclorotiazida, Clortalidona, Indapamida.
Ação diurética moderada (são mais seguros). Seu mecanismo de ação é inibir a ação do íon transportador Na+CL- no túbulo distal com aumento de eliminação de Na+, Cl-, K+ e água.
Interações Medicamentosas:
*Reduzem os efeitos: Anticoagulantes, Insulina.
*Aumentam os efeitos: Glicosídeos digitálicos, Diuréticos de alça.
*AINEs reduzem seu efeito diurético


Diuréticos poupadores do potássio

Esses são os diuréticos que não promovem a secreção de potássio pela urina. Desta forma, o potássio não é perdido tanto quanto com o uso de outros diuréticos. São diuréticos que eliminam sódio e água, porém poupam o potássio. Agem inibindo os canais condutores de sódio no túbulo coletor (inibem a reabsorção de Na+ e diminuem a excreção de K+, mas possuem ação diurética limitada), como a amilorida e triantereno ou bloqueando a aldosterona (compete pelos receptores intracelulares de aldosterona e possui inicio de ação lenta), como a espironolactona.

ASSIM..

O mecanismo de ação anti-hipertensiva dos diuréticos relaciona-se inicialmente aos seus efeitos diurético e natriurético (eliminação de líquidos e sal pela urina). Posteriormente, após cerca de 4 a 6 semanas, o volume circulante de líquidos praticamente se normaliza e há redução persistente da resistência dos vasos sanguíneos.
Como anti-hipertensivos são preferidos os diuréticos tiazídicos e similares, em baixas doses (hidroclortiazida 12,5 mg/dia ou 25 mg/dia). Os diuréticos de alça (furosemida) são reservados para situações de hipertensão arterial associada à insuficiência renal e na insuficiência cardíaca com retenção de líquidos.
Os diuréticos poupadores de potássio (espironolactona) apresentam pequena eficácia diurética, mas, quando associados aos tiazídicos e aos diuréticos, são úteis na prevenção e no tratamento de hipopotassemia (queda do potássio).

Reações adversas principais dos diuréticos: hipopotassemia (queda dos níveis de potássio, por vezes acompanhada da queda dos níveis de magnésio, que pode induzir arritmias cardíacas ventriculares) e hiperuricemia (elevação do ácido úrico no sangue).
O emprego de baixas doses diminui o risco de efeitos adversos, sem prejuízo da eficácia anti-hipertensiva. Os diuréticos também podem provocar intolerância à glicose (aumentar os níveis de glicemia - característico dos tiazídicos), além de promoverem aumento dos triglicerídeos, em geral, dependente da dose e de duração do tratamento.

E a aldosterona, citada ao longo do estudo? Qual sua função?


A Aldosterona é um hormônio do grupo dos esteróides, produzido nas glândulas suprarrenais, cuja capacidade mineralocorticoide o torna o principal controlador da absorção/excreção de sódio e potássio, atuando na regulação dos fluídos corpóreos. Sua ação diminui a excreção de sódio e aumenta a excreção de potássio pelos rins, sudorese e saliva. Em cada tecido alvo, incluído o intestino grosso e os tubos coletores do córtex renal, a Aldosterona liga-se a receptores mineralocorticoides. A regulação homeostática do sódio e potássio é obtida um complexo conjunto de hormônios, que atuam por ciclos de realimentação/retroalimentação. 


Referências bibliográficas utilizadas

Farmacologia dos diuréticos: 
http://www.uff.br/farmacobasica-mfl/sites/default/files/12_diureticos_ds.pdf
Clínica médica cardiologia - Medicamentos anti-hipertensivos:
http://www.cfcp.com.br/a/index.asp?n=35793&lg=pt
Anotações em farmacologia e farmácia clínica
http://farmacolog.dominiotemporario.com/doc/cap_5_-_Farmacos_antihipertensivos.pdf
Diuréticos
http://sociedades.cardiol.br/socerj/area-cientifica/diureticos.asp




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