Pulmoner Arteriyel Hipertansiyonda Farmakolojik Tedavi
Özet
Pulmoner arteriyel hipertansiyon (PAH), pulmoner arterlerde ilerleyici yeniden şekillenme, vazokonstriksiyon ve yerinde tromboz ile karakterize; tedavi edilmediğinde sağ ventrikül yetmezliği ve ölümle sonuçlanan ağır bir pulmoner damar hastalığıdır. Hastalığın patobiyolojisinde endotelin, nitrik oksit–siklik guanozin monofosfat (NO–cGMP) ve prostasiklin yolaklarındaki işlev bozukluğu merkezi rol oynar ve güncel farmakoterapi tam olarak bu üç yolağı hedef almaktadır. Bu bölümde endotelin reseptör antagonistleri (bosentan, ambrisentan, masitentan), fosfodiesteraz tip-5 inhibitörleri (sildenafil, tadalafil), çözünür guanilat siklaz stimülatörü riosiguat ve prostanoidler/prostasiklin reseptör agonistleri (epoprostenol, treprostinil, iloprost, selexipag) etki mekanizmaları, pivotal klinik çalışma kanıtları ve güvenlik profilleri bakımından ayrıntılı biçimde ele alınmıştır. Ayrıca vazoreaktivite testinde yanıt veren seçilmiş hastalarda yüksek doz kalsiyum kanal blokerlerinin yeri, başlangıç ve ardışık kombinasyon tedavi stratejileri, çok parametreli risk temelli tedavi yaklaşımı ve aktivin sinyal yolağını hedefleyen yeni ajan sotatersept özetlenmiştir. Sonuç olarak PAH farmakoterapisi; risk değerlendirmesine dayanan, çoğunlukla tanı anından itibaren kombinasyon biçiminde uygulanan ve izlemde düzenli olarak yeniden gözden geçirilen dinamik bir tedavi süreci olarak tanımlanmaktadır.
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by progressive remodeling of small pulmonary arteries, vasoconstriction, and in situ thrombosis, which leads to right ventricular failure and death if left untreated. Dysfunction of three interrelated signaling pathways—endothelin, nitric oxide–cyclic guanosine monophosphate (NO–cGMP), and prostacyclin—plays a central role in disease pathobiology and forms the basis of contemporary pharmacotherapy. This chapter reviews the mechanisms of action, pivotal clinical trial evidence, and safety profiles of endothelin receptor antagonists (bosentan, ambrisentan, macitentan), phosphodiesterase type-5 inhibitors (sildenafil, tadalafil), the soluble guanylate cyclase stimulator riociguat, and prostanoids/prostacyclin receptor agonists (epoprostenol, treprostinil, iloprost, selexipag). The role of high-dose calcium channel blockers in vasoreactivity-responsive patients, initial and sequential combination therapy strategies, multiparametric risk-based treatment algorithms, and the emerging activin pathway-targeting agent sotatercept are also discussed. Overall, PAH pharmacotherapy is presented as a dynamic, risk-stratified process that is increasingly delivered as combination therapy from the time of diagnosis and continuously reassessed during follow-up.
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