Pulmonary hypertension (PH) is a life threatening, progressive disease in which there is elevated blood pressure in the arteries supplying the lungs. The blood flow from the heart to the lungs is disrupted due to constriction in blood vessels causing elevated pulmonary arterial pressure. Pressure in pulmonary arteries above 30 mm Hg is considered pulmonary hypertension.
Causes of Secondary Pulmonary Hypertension
Pulmonary hypertension can be idiopathic, known as primary pulmonary hypertension and when it is results due to other diseases, it is known as secondary pulmonary hypertension.
The different causes of secondary pulmonary hypertension include autoimmune diseases (rheumatoid arthritis and SLE), connective tissue diseases (scleroderma, CREST syndrome, lupus), liver diseases, congenital heart diseases (atrial and ventricular septal defects), HIV infection and schistosomiasis. It can be caused due to drugs including diet pills (such as fenfluramine and dexfenfluramine) and recreational drugs. It can also be caused by various lung conditions such as chronic obstructive pulmonary disease (COPD), emphysema, pulmonary fibrosis (interstitial lung diseases) and sleep apnea. In addition, it can also be caused by clotting disorders such as pulmonary emboli. Heart failure and other conditions affecting left side of the heart including mitral valve disease and chronic systemic elevated blood pressure can also cause secondary PH. The causes also include blood disorders (polycythemia vera and thrombocythemia), metabolic disorders (thyroid diseases and glycogen storage disease), systemic disorders (sarcoidosis and vasculitis), and kidney diseases.
What are the Newer Medicines available for Pulmonary Hypertension?
Pulmonary hypertension is a progressive disease, which is life threatening if left untreated with a survival rate of only 2-3 years in the absence of management. There have been advances in treatment modalities with the survival rate rising to 5-10 years and more medications in the market. There is no definitive treatment for pulmonary hypertension, but new advances in this field hold promise. The first medication was introduced in 1994 in the form of Flolan for the management of pulmonary hypertension and since then there have been various medications in the market. The aim of treatment is slowing the progression of disease by improving the quality of life of the patient with medications. The goal of treatment is to treat the underlying cause and reduce symptoms of elevated pulmonary pressure in blood vessels in order to improve quality of life of the patients.
PH shows an imbalance between endothelial derived vasodilators and vasoconstrictors that causes pulmonary vasoconstriction and vascular proliferation. The current treatment options aim at restoring this imbalance, which include:
Phosphodiesterase-5 inhibitors (PDE 5) inhibitors cause vasodilatation of the pulmonary blood vessels by facilitating cGMP and NO. PDE 5 inhibitors used are sildenafil (Revatio) and tadalafil (Adcirca) in oral form.
Prostacyclin Analogue reduces blood pressure by relaxation of pulmonary blood vessels. The prostacyclin used is treprostinil, which can be taken orally (Orenitram), inhaled (Tyvaso), IV (Remodulin), and subcutaneously.
Endothelin Receptor Antagonists (ERAs) prevent vasoconstriction. They are usually taken orally and the various ERAs used are ambrisentan (Letairis), macitentan (Opsumit) and bosentan (Tracleer).
Selective IP Receptor Agonist helps in relaxing blood vessels in the lungs by activating prostacyclin receptor. The example is selexipag (Uptravi) taken orally.
Soluble Guanylate Cyclase (sGC) relaxes pulmonary blood vessels by increasing interaction of sGC with NO. Example includes riociguat (Adempas).
Intravenous medications include Flolan (epoprostenol), Remodulin and Veletri. Ventavis and Tyvaso are used in inhaled form for relief of shortness of breath.
Other treatment options include calcium channel blockers, anticoagulants in the form of warfarin (Coumadin). Digoxin is used for better heart pumping, diuretics for extra fluid removal from the body and artificial oxygen when needed.
The last option for severe cases of PH is lung transplant. There have been major advances in PH treatment in the past decade. Newer therapies such as stem cell therapy, Rho kinase pathway, tyrosine kinase pathway (imatinib), adrenomedullin, dichloroacetate, angiopoietin, carbonic anhydrase inhibitors (topiramate), serotonin, vasoactive intestinal peptide (VIP), simvastatin, and cicletanine are all under trial and research.