Table 1.

The side effects and damage of major PAH-specific therapies

Major targeted pathways	Compounds	PAH-specific drugs	Administration routes	The side effects and damages
				Related to the administration routes	Related to the pharmacological action
					More frequent	Others
Endothelin pathway	ERAs	Bosentan	Oral	–	Liver transaminase elevation	Flushing, headaches dizziness, peripheral edema, palpitations, chest pain, nasopharyngitis, anemia
		Ambrisentan	Oral	–	Peripheral edema	Nasal congestion, upper respiratory tract infection, nausea, sinusitis, nasopharyngitis, flushing, headaches, liver transaminase elevation, abdominal pain, constipation, palpitations, dyspnea
		Macitentan	Oral	–	Headaches, nasopharyngitis, anemia	Peripheral edema, anemia, upper respiratory tract infection, dizziness, bronchitis, dyspnea, cough, liver transaminase elevation
		Sitaxentan*	Oral	–	Acute liver toxicity	Nasal congestion, flushing
Nitric oxide-cGMP pathway	PDE-5 inhibitors	Sildenafil	Oral	–	Headaches, flushing, epistaxis	Left ventricular dysfunction, postural hypotension, dyspepsia, back pain, diarrhea, extremity pain, myalgia, cough, pyrexia, insomnia, influenza, visual disturbance, grand mal seizure, drug hypersensitivity, urticaria, angioedema, gastroesophageal reflux disease, posterior subcapsular cataract, neck stiffness, abdominal pain
			Intravenous	–	Flushing	Flatulence, hypotension, syncope
		Tadalafil	Oral	–	Headaches, myalgia, flushing	Diarrhea, nausea, back pain, dyspepsia, dyspnea, extremity pain, muscle spasms, upper respiratory tract infection, epistaxis, palpitations, arthralgia, chest pain, vomiting, fatigue, nasal congestion, edema, bronchitis, insomnia, urinary tract infection, blurred vision
	sGC stimulators	Riociguat	Oral	–	Headaches, flushing, hypotension	Dyspepsia, peripheral edema, nausea, syncope, bleeding (including hemoptysis), dizziness, diarrhea, vomiting, nasopharyngitis, anemia, palpitations, chest pain, dyspnea, gastroesophageal reflux disease, cough, nasal congestion, pyrexia, fatigue, chest discomfort, gastritis
Prostacyclin pathway	Prostacyclin analogs	Epoprostenol	Continuous intravenous infusion	Catheter-related infections, sepsis, thromboembolic event, irritation, bleeding, drug-delivery system malfunction	Jaw pain, diarrhea, flushing	Headaches, nausea, vomiting
		Iloprost	Inhaled	Increased cough	Flushing, jaw pain, headaches	Hypotension, influenza-like syndrome, peripheral edema, nausea, diarrhea, dizziness
		Treprostinil	Oral	–	Headaches, flushing, nausea	Diarrhea, jaw pain, vomiting, extremity pain
			Continuous subcutaneous infusion	Severe infusion site pain, reaction, bleeding and bruising	Diarrhea, jaw pain, flushing	Peripheral edema, nausea, rash, dizziness, vomiting, headaches, vasodilatation
			Continuous intravenous infusion	Catheter-related blood stream infection, thromboembolic event, irritation, bleeding, drug-delivery system malfunction	Extremity pain, headaches, diarrhea	Jaw pain, nausea, fatigue, loose stools, vomiting, dizziness, dyspnea, flushing, palpitations, peripheral edema
			Inhaled	Cough, throat irritation,	Headaches, nausea,	Flushing, diarrhea, anemia, abdominal pain, diabetes mellitus,
				pharyngolaryngeal pain	dizziness	gastric ulcer
		Beraprost	Oral	–	Headaches, flushing, jaw pain	Diarrhea, extremity pain, nausea, pharyngitis, asthenia, palpitations, vasodilatation

Note:

^*Sitaxentan was withdrawn from the market in 2010 because of an increasing number of deaths attributed to acute liver toxicity. –, not applicable.

Abbreviation: PAH, pulmonary arterial hypertension.