Table 2.

Pulmonary hypertension targeted drug therapies.

Drug	Dose	Mechanism of Action	Adverse Reactions	Indications
Inhaled Nitric Oxide	Inhalation 5–20 ppm	- Activates sGC in vascular smooth muscle cells - Selective Pulmonary Vasodilator	- Rebound PH with rapid discontinuation - Methemoglobinemia with higher doses	Hypoxemic respiratory failure with PPHN physiology
Sildenafil	Intravenous - Loading Dose: 0.4 mg/kg over 3 h - Maintenance: 0.067 mg/kg/h Enteral - Initial Dose 0.5 mg/kg/dose followed by increasing to 1–2 mg/kg every 6–8 h	- Selective PDE5 inhibition increases vascular smooth muscle cGMP levels - Pulmonary Vasodilator	- Hypotension (particularly with loading dose) - Hypoxemia	PPHN refractory to inhaled nitric oxide therapy and other conventional therapies
Milrinone	Intravenous - Initial Infusion Dose: 0.2–0.33 μg/kg per minute - Dose Titration: Increase by 0.33 μg/kg per minute to a maximum of 1 μg/kg per minute	- PDE3 inhibition increases vascular smooth muscle cAMP levels - Improves cardiac performance through pulmonary vasodilation, systemic afterload reduction, and enhanced lusitropy	- Hypotension - Thrombocytopenia - Arrhythmias	Left ventricular dysfunction associated with PPHN
Bosentan	Enteral 1 –2 mg/kg every 12 h	- Dual ETA and ETB receptor inhibitor	- Hepatotoxicity: Monitor LFTs monthly - Edema - Anemia - Teratogenic	PPHN refractory to iNO and other therapies Chronic PH (CDH, BPD)
Prostanoids	Treprostinil (Remodulin) - Initial Infusion Dose: 1.25 ng/kg per minute - Dose titration: Slowly increase to 10 ng/kg per minute *Can be delivered subcutaneously in the same dosing range Epoprostenol (Flolan) - Inhaled: 20–100 ng/kg per minute. Start at 2 ng/kg per minute and increase to 20 ng/kg per minute within 3 h - Continuous Intravenous Infusion: 1–2 ng/kg per minute, incremental increases as tolerated	- Activates sAC in vascular smooth muscle cells - Pulmonary Vasodilator	Ventilation–perfusion mismatch may complicate use in the setting of lung disease. Nonselective vasodilator, can cause systemic hypotension Risk of rebound PH with sudden withdrawal Flushing, diarrhea	PPHN refractory to iNO and other therapies

sCG, soluble guanylate cyclase; PH, pulmonary hypertension; PPHN, persistent pulmonary hypertension of the newborn; PDE5, phosphodiesterase 5; cGMP, cyclic GMP; PDE3, phosphodiesterase 3; cAMP, Cyclic AMP; ET, endothelin; LFT, liver function test; iNO, inhaled nitric oxide; BPD, bronchopulmonary dysplasia; CDH, congenital diaphragmatic hernia; sAC, soluble adenylate cyclase.