PULMONARY HYPERTENSION

Pulmonary hypertension is abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart need to work harder than normal.


                                                                               (or)


pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to 
shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance and heart failure .


According to the most recent classification, it can be one of five different types: arterial, venous, hypoxic, thromboembolic or miscellaneous.


Pulmonary arterial hypertension (PAH) is a disease characterized by an increase of pulmonary vascular resistance leading to right-sided heart failure and premature death. There are two kinds of pulmonary hypertension: primary pulmonary arterial hypertension (PPAH), which has no known causes, andsecondary pulmonary arterial hypertension (SPAH), which is either caused by or occurs because of another condition.

TREATMENTS:

ENDOTHELIN RECEPTOR ANTAGONIST

–Endothelin-1 (ET-1) is a neurohormone, the effects of which are mediated by binding to ET_A and ET_B receptors in the endothelium and vascular smooth muscle. ET-1 concentrations are elevated in plasma and lung tissue of patients with PAH, suggesting a pathogenic role for ET-1 in this disease.

–The primary actions of ET_A are vasoconstriction and cell proliferation, while the predominant actions of ET_B are vasodilation, antiproliferation, and ET-1 clearance.

–Ambrisentan is a high affinity ET_A receptor antagonist with a high selectivity for the ET_A versus ET_B receptor.

–Bosentan is a specific and competitive antagonist at endothelin receptor types ET_A and ET_B, with a slightly higher affinity for ET_A than ET_B receptors.

PROSTACYLCIN (PGI2)

–Dilates systemic and pulmonary arterial vascular beds; inhibits platelet aggregation

–Epoprostenol, a naturally occurring prostaglandin, is infused continuously through a permanent indwelling catheter; long term therapy may delay or prevent need for lung or lung-heart transplant

–Iloprost, a synthetic analogue of prostacyclin PGI2, is formulated for inhalation via either of two pulmonary drug delivery devices: the I-neb AAD System or the Prodose AAD System

–Treprostinil is a prostacyclin analogue available as both an oral inhalation therapy (Tyvaso) and as an SC or IV continuous infusion (Remodulin)


PHOSPHODIESTERASE TYPE-5 (PDE5) INHIBITOR


–Revatio (sildenafil citrate), Adcirca (tadalafil), both oral therapies for PAH

–Causes vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilation in the systemic circulation

–Metabolized via cytochrome P450 (CYP3A4); toxicity may be enhanced if given with drugs that are substrates of this enzyme