An overview of the three major therapeutic pathways in pulmonary arterial hypertension
| Therapeutic pathways | Nitric oxide (NO) | Prostacyclin (PGI2) | Endothelin 1 (ET1) |
| Levels in PAH | Reduced | Reduced | Increased |
| Aim of therapy | To increase NO | To increase PGI2 | To reduce ET1 |
| Current available drugs | Sildenafil | Epoprostenol | Macitentan |
| Tadalafil | Treprostinil | Ambrisentan | |
| Riociguat | Iloprost | Bosentan | |
| Selexipag | |||
| Routes of administration | Oral | Oral, parenteral, inhaled | Oral |
| Method of action | To increase cGMP via the inhibition of PD5 or by direct stimulation of sGC | To increase the conversion of ATP to cAMP | To inhibit ETA receptors ± ETB receptors |
| Side-effects | |||
| Common side-effects | Systemic vasodilation resulting in hypotension, flushing, light-headedness, gastrointestinal side-effects (e.g. nausea, diarrhoea) | ||
| Specific drug side-effects | Sildenafil and tadalafil: ocular side-effects | Parenteral prostacyclin: thrombocytopenia, bone marrow suppression | Macitentan: anaemia Bosentan: deranged transaminases |
| Rash | |||
The aim of therapy is to promote vasodilation in the pulmonary circulation. Within the nitric oxide pathway, sildenafil and tadalafil are phosphodiesterase type-5 (PD5) inhibitors and riociguat is a soluble guanylate cyclase (sGC) stimulator. In the endothelin (ET) pathway, bosentan and macitentan are dual ET receptor antagonists (i.e. they block both ETA and ETB receptors) and ambrisentan is a selective ETA receptor antagonist. Modern therapy typically consists of double or triple combination therapy, using one drug from each therapeutic pathway. Monotherapy is uncommon and should only be considered in patients with low-risk profiles. cGMP: cyclic guanosine monophosphate.