Pulmonary Hypertension Treatments

Treatments for pulmonary hypertension

Treatments for pulmonary arterial hypertension currently include continuously infused, inhaled, and oral medications. Some of these medications are exclusively for the treatment of pulmonary hypertension while others are general medications that are also beneficial in PH patients.

The use of blood thinners in the treatment of pulmonary hypertension

Blood thinners such as coumadin are commonly used to prevent or treat blood clots and are useful in the treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension as the narrowed pulmonary arteries are prone to blood clots. The risks and benefits of any medication should be discussed before placing a patient on therapy and this is very important before initiating blood thinners as there are serious risks associated with these medications. It is very important to perform regular blood tests (INRs) to measure how thin the blood is to avoid serious complications. If the blood is too thin (INR is too high) the patient is at risk for bleeding complications and if is too thick (INR is too low) they remain at risk of blood clots.

Diuretics or “water pills” in the treatment of pulmonary hypertension

PAH medicationsDiuretics are commonly used to help treat heart failure. Because the right ventricle of pulmonary arterial hypertension patients is straining to pump against the increased pressures in the pulmonary arteries, they have the same volume management problem. Diuretics help eliminate excess fluid in the body that would normally naturally be eliminated by an efficient heart and kidneys. There are many types of diuretics such as Lasix, Aladactone, Bumex, and Metolazone. It is important to take diuretics as they have been prescribed because excess amounts may cause a decrease in electrolytes such as potassium and damage to the kidneys. Routine blood work such as a BMP should be performed while taking diuretics. Close management of salt and water restrictions continue to apply even if a diuretic has been prescribed. Generally only one physician should be prescribing, monitoring, and changing a patient’s diuretic regime.

Three pathways for treating pulmonary hypertension

Currently there are three known pathways that play a part in cell proliferation and vasoconstriction in the pulmonary arteries of patients with pulmonary arterial hypertension. Treatments for PAH are aimed at these pathways. Since each class of drug only targets one of the three pathways it is very common for pulmonary hypertension patients to be on combination therapy so two or all three of the pathways are targeted. Only one drug from each class of drug should be used at a time but up to three classes of drugs may be used in combination.

Prostacyclin pathway in pulmonary hypertension

Prostacyclin is a potent vasodilator (opening the blood vessels) that also inhibits the cells in the middle of the blood vessels from growing into lesions and helps keep platelets in the blood from sticking to the edges of the damaged blood vessels. PAH patients have a deficiency of prostacyclin. Drugs targeting this pathway are called prostacyclins and their goal is to increase the level of prostacylin in the body. Drugs currently FDA approved in this classification include Flolan (Epoprostenil), Veletri (Epoprostenil), Remodulin (Treprostinil), Ventavis (Iloprost), Tyvaso (Treprostinil), and Orenitram (Trepostinil). Until recently this class of drug was only available via continuous infusion or inhalation. Orenitram was the first oral option in this class approved by the FDA for the treatment of pulmonary arterial hypertension.

Endothelin pathway in pulmonary hypertension

Endothelin is a known potent vasoconstrictor (making the blood vessels smaller and the pressure necessary to push blood through higher) that also promotes the cells in the middle of the blood vessels to grow and form lesions. The class of drugs that targets this pathway is called Endothelin Receptor Antagonist (ERAs). They work by blocking the receptors in the blood vessels from responding to endothelin. There are currently three ERAs approved by the FDA for treatment of pulmonary arterial hypertension: Tracleer (Bosentan), Letairis (Ambresentan), and Opsumit (Macitentan).  All three are pills taken orally.

Nitric oxide pathway in pulmonary hypertension

Nitric oxide is a potent vasodilator (relaxes the blood vessels, opening them and making it easier for blood to flow through). Pulmonary hypertension patients have a decreased production of nitric oxide in their bodies. There are two classes of medications that target this pathway. Phosphodiesterase type 5 is a molecule in the body that interrupts the production of nitric oxide. The drugs that target this pathway are called phosphodiesterase type 5 inhibitors or PDEV inhibitors. They work by inhibiting or decreasing the effect of phosphodiesterase type 5 allowing for higher concentrations of nitric oxide to remain in the blood vessels. Soluble guanylate cyclase stimulators (sGC) work by stimulating an enzyme inside cells called soluble guanylate cyclace.  By increasing the activity of this enzyme, there is an increase in the production of cyclic GMP, which in turn leads to relaxation of the pulmonary arteries and improvements in pulmonary hypertension.  The pathway by which soluble guanylate cyclase stimulators work is similar to the way in which PDEV inhibitors work but the action is at an earlier point in the cascade.  Currently the FDA has approved two PDEV inhibitors Revatio (Sildenafil) and Adcirca (Tadalafil), and one soluble guanylate cyclase stimulator Adempas (Riociguat).  All three medications are taken orally.