This delivery system can cause sepsis and thrombosis. Prostacyclin is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous, and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC. Iloprost is also used in Europe intravenously and has a longer half life. Iloprost was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil was approved by the FDA in July 2009. Endothelin receptor antagonists
Moderate quality evidence suggests that endothelin receptor antagonists improve exercise capacity and decrease symptoms severity. The dual (ETA and ETB) endothelin receptor antagonist bosentan was approved in 2001. Sitaxentan (Thelin) was approved for use in Canada, Australia, and the European Union, but not in the United States. In 2010, Pfizer withdrew Thelin worldwide because of fatal liver complications. A similar drug, ambrisentan is marketed as Letairis in the U.S. by Gilead Sciences. s

Phosphodiesterase type 5 inhibitors
The U.S. FDA approved sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved tadalafil, another PDE5 inhibitor, marketed under the name Adcirca.
Importantly, right ventricular remodeling is associated with increased apoptosis; this is in contrast to pulmonary vascular remodeling which involves inhibition of apoptosis. Diagnosis
In terms of the diagnosis of pulmonary hypertension, it has five major types, and a series of tests must be performed to distinguish pulmonary arterial hypertension from venous, hypoxic, thromboembolic, or unclear multifactorial varieties. PAH is diagnosed after exclusion of other possible causes of pulmonary hypertension. Physical examination
A physical examination is performed to look for typical signs of pulmonary hypertension (described above), and a detailed family history is established to determine whether the disease might be heritable. A history of exposure to drugs such as benfluorex (a fenfluramine derivative), dasatinib, cocaine, methamphetamine, ethanol leading to cirrhosis, and tobacco leading to emphysema is considered significant. Use of selective serotonin reuptake inhibitors during pregnancy (particularly late pregnancy) is associated with an increased risk of the baby developing persistent pulmonary hypertension of the newborn. Echocardiography
If pulmonary hypertension is suspected based on the above assessments, echocardiography is performed as the next step. A meta-analysis of Doppler echocardiography for predicting the results of right heart catheterization reported a sensitivity and specificity of 88% and 56%, respectively. Thus, Doppler echocardiography can suggest the presence of pulmonary hypertension, but right heart catheterization (described below) remains the gold standard for diagnosis of PAH. Echocardiography can also help to detect congenital heart disease as a cause of pulmonary hypertension.