Pharmacotherapeutic Management of Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a disabling chronic disorder of the pulmonary vasculature, which is characterized by increased pulmonary artery pressure as a result of increased pulmonary vascular resistance. The pathology of PAH is characterized by pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. These changes are a result of an imbalance between vasodilators (prostacyclin, nitric oxide, vasoactive intestinal peptide) and vasoconstrictors (thromboxane A2, endothelin, serotonin), growth inhibitors and mitogenic factors, and antithrombotic and prothrombotic factors. Recent advances in treatment are directed at restoring the balance between these systems. Endothelin receptor antagonists (bosentan, ambrisentan, sitaxsentan), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil), and prostacylin (epoprostenol, iloprost, treprostinil, beraprost) represent the different classes of medications that are currently used in monotherapy and in combination to treat PAH. The purpose of this drug highlight is to provide the reader with an update of the pharmacotherapeutic treatment of PAH.

Molecular Mechanisms of Pulmonary Arterial Remodeling

“…The exact molecular mechanism of PAH has yet to be resolved. Median survival rates have improved with the recent introduction of endothelin receptor antagonists (ERAs) and phosphodiesterase (PDE)-5 inhibitors, but a recent estimate of survival of 3.6 years is still discouraging (1). To manage PAH successfully, the reversal or inhibition of pulmonary vascular remodeling must be achieved.…”

Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

“…Hipotansiyon (<90/50mmHg), volüm eksiği olanlar, şiddetli sol çıkış yolu darlığı olanlar ve otonomik disfonksiyonu olanlarda dikkatli kullanılmalıdır (9). Hipotansiyon riski nitrogliserin, alfa adrenerjik bloker, amlodipin gibi diğer vazodilatatörlerle beraber kullanıldığında artar.…”

“…Şiddetli hipotansiyon riski nedeniyle nitrogliserin ile birlikte kullanımı kontraendikedir (9). Alfa adrenerjik bloker, amlodipin gibi diğer vazodilatatörlerle kullanımında hipotansiyon açısından dikkatli olunmalıdır.…”

Prostanoids in the treatment of pulmonary arterial hypertension

“…PAH'ta birçok ilaç kombinasyonları çalışılmıştır ve çalışmalar genelde çok etkili olmayan bir ilaca diğer bir sınıf ilacın eklenmesiyle yapılmıştır, ancak bu çalışmaların çoğu yeterli büyüklükte değildir, randomize veya kontrollü değildir (7).…”

“…Pulmoner hipertansiyon (PH) tromboksan A2 oluşmasındaki artışla karakterizedir, ayrıca pulmoner arterlerde prostasiklin sentetaz'da da azalma mevcuttur (7).…”