Perspektywy leczenia farmakologicznego tętniczego nadciśnienia płucnego

Autorzy

Witold Kimla
Śląski Uniwersytet Medyczny
Daniel Kiełtyka

Słowa kluczowe:

tętnicze nadciśnienie płucne, PAH, farmakoterapia, patogeneza

Streszczenie

Tętnicze nadciśnienie płucne(ang. pulmonary arterial hypertension, PAH) to nieprawidłowy wzrost ciśnienia w tętnicy płucnej spowodowany zaburzeniem funkcji przedkapilarnej części krążenia płucnego. Nieleczone nadciśnienie płucne szybko prowadzi do rozwoju prawokomorowej niewydolności serca i wiąże się z średnim czasem przeżycia wynoszącym 3 lata w przypadku idiopatycznego tętniczego nadciśnienia płucnego. Obecnie stosowana farmakoterapia opiera się na lekach działąjących na 3 szlaki uczestniczące w patogenezie PAH: szlak endoteliny, szlak tlenku azotu-cGMP i szlak prostacykliny-cAMP. Ich dominującym mechanizmem działania jest hamowanie wazokonstrykcji łożyska płucnego. Poprawiają one komfort życia pacjentów i ich przeżywalność jednak nadal wyniki leczenia nie są satysfakcjonujące- co piąty chory na PAH umiera w ciągu 2 lat od zdiagnozowania choroby i rozpoczęcia leczenia. Rozwój wiedzy na temat etiopatogenezy PAH pozwolił na odkrycie nowych potencjalnych punktów uchwytu dla leczenia farmakologicznego. Obecnie bada się rolę białek należących do nadrodziny transformujących czynników wzrostu beta, w tym białka morfogenetyczne kości(ang. bone morphogenetic proteins, BMPs) działające przez szlak BMP/SMAD. Bada się też wpływ kinaz tyrozynowych, kinaz rho, estrogenów, serotoniny, elastazy serynowej i wielu innych na rozwój i przebieg PAH. Szlaki BMP/SMAD, kinaz tyrozynowych, kinaz rho uczestniczą w remodelingu łożyska płucnego. Cząsteczki modulujące te mechanizmy molekularne mają szansę stać się lekami hamującymi lub odwracającymi przebudowę naczyń krążenia płucnego, wpływając na tę komponentę choroby która jest obecnie leczona w niewystarczającym stopniu. Celem pracy jest zaprezentowanie rezultatów dotychczasowych badań nad nowymi lekami które obejmują ich skuteczność i domniemany mechanizm działania

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26 marca 2023