Table 1.

Food and Drug Administration-approved medication for pulmonary arterial hypertension

Therapeutic class	Drug	Mechanism of action	Available forms	Common adverse events	Clinical trials
Phosphodiesterase 5 inhibitors	Sildenafil	Enhances the nitric oxide–cGMP pathway and slows cGMP degradation; acts as pulmonary vasodilator	Oral, intravenous	Headache (16–46%), flushing (10–19%), dyspepsia (3–17%), epistaxis (9–13%), hypotension (< 2%)	Izbicki et al. (2006) [14] Galiè et al. (2005) [15] McLaughlin et al. (2015) [16] Iversen et al. (2010) [17] Vizza et al. (2017) [18] Ling-Yun AI et al. (2016) [19] Zhu et al. (2018) [20] Bermejo et al. (2018) [21]
	Tadalafil	Enhances the nitric oxide–cGMP pathway and slows cGMP degradation; acts as pulmonary vasodilator	Oral	Headache (4–46%), flushing (2–13%), nausea (11%), myalgia (1–14%), hypotension (< 2%)	White et al. (2019) [22] Galiè et al. (2015) [23] Kuwana et al. (2020) [24] Guo et al. (2018) [25] De-Zhen Z. et al. (2020) [26] Zhuang et al. (2014) [27] Barst et al. (2011) [28]
Endothelin receptor antagonists	Bosentan	Binds to endothelin receptors, types A and B; blocks endothelin-mediated vasoconstriction	Oral	Increased hepatic transaminases (about 12%; dose dependent), edema (11%), respiratory tract infections (22%), fluid retention (< 3%)	Baughman et al. (2014) [29] Rubin et al. (2002) [30] Galiè et al. (2002) [31] Badesch et al. (2002) [32] Galiè et al. (2008) [33] Ni AI et al. (2018) [25] De-Zhen et al. (2020) [24] Guo et al. (2018) [34] McLaughlin et al. (2006) [35] Hoeper et al. (2006) [36] Wilkins et al. (2005) [27] Barst et al. (2011) [28]
	Ambrisentan	Binds to endothelin receptors types A and B; blocks endothelin-mediated vasoconstriction	Oral	Peripheral edema (14–38%), abdominal liver function test results (< 1%), anemia (7%), cough (13%)	Galiè et al. (2008) [38] White et al. (2019) [22] Galiè et al. (2015) [23] Kuwana et al. (2020) [26] Zhuang et al. (2014) [38]
	Macitentan	Binds to endothelin receptors types A and B; blocks endothelin-mediated vasoconstriction	Oral	Anemia (13%), headache (14%), nasopharyngitis (20%), increased liver enzymes	Gatzoulis et al. (2019) [39] Pulido et al. (2013) [40] Sitbon et al. (2019) [41] Jansa and Pulido (2018) [42]
Guanylate cyclase stimulator	Riociguat	Enhances cGMP production; acts as a vasodilator	Oral	Hypotension (3–10%), headache (27%), dizziness (20%), respiratory hemoptysis (1%), epistaxis	Galiè et al. (2015) [43] Rubin et al. (2015) [44] Rosenkranz et al. (2015) [45] Humbert et al. (2017) [46] Ghofrani et al. (2013) [47]
Prostacyclin analogs and prostacyclin receptor agonists	Epoprostenol	Mimics endogenous prostacyclin; potent vasodilator, inhibits platelet aggregation	Continuous intravenous infusion	Flushing (23–58%), headache (46–83%), diarrhea (37–50%), jaw pain (54–75%), musculoskeletal pain (3–84%), potential for line-associated complications	Badesch (2000) [48] Barst et al. (1996) [49] Barst (1997) [50] Humbert et al. (2004) [51]
	Treprostinil	Mimics endogenous prostacyclin; potent vasodilator, inhibits platelet aggregation	Continuous intravenous infusion, continuous subcutaneous infusion, inhaled via specialized nebulizer	Flushing (15–45%), headache (27–75%), diarrhea (25–69%), jaw pain (11–18%), limb pain with all forms (14–18%), potential line-associated complications with subcutaneous form (83%), cough with inhaled form (54%)	McLaughlin et al. (2010) [52] White et al. (2019) [22] Jing et al. (2013) [53] Hiremath et al. (2010) [54] Ronald (2004) [55] Tapson et al. (2012) [56]
	Iloprost	Mimics endogenous prostacyclin; potent vasodilator, inhibits platelet aggregation	Inhaled via specialized nebulizer	Flushing (27%), headache (30%), jaw pain (12%), cough (39%)	McLaughlin et al. (2006) [35] Hoeper et al. (2006) [36]
	Selexipag	Mimics endogenous prostacyclin; potent vasodilator, inhibits platelet aggregation	Oral	Flushing (12%), headache (65%), diarrhea (42%), jaw pain (26%)	Simonneau et al. (2012) [57] Coghlan et al. (2018) [58] Sitbon et al. (2015) [59]