Medication Summary
Treatment for idiopathic pulmonary artery hypertension (IPAH) has significantly improved over the past 20 years. Therapy now offers children with idiopathic pulmonary artery hypertension hope for a much better prognosis and a relatively reasonable quality of life. Pharmacologic therapy includes anticoagulants, positive inotropic agents, and vasodilators.
Anticoagulants
Class Summary
Adult studies have suggested that long-term anticoagulation with warfarin to achieve an international normalized ratio (INR) of 2.5-3 decreases the morbidity and mortality rates associated with IPAH. This is based on the pathologic finding of microthrombi in the pulmonary vasculature. Whether this is a primary or secondary finding is not known. The major precautions relate to bleeding risks.
Warfarin (Coumadin)
Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors.
Positive Inotropic Agents
Class Summary
The use of an oral inotropic agent is advocated in patients with right ventricular dysfunction that is associated with IPAH.
Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
PAH, PDE-5 Inhibitors
Class Summary
Inhibition of the antiproliferative effects of the phosphodiesterase-5 (PDE-5) pathway, which regulates cyclic guanosine monophosphate hydrolysis, may be significant in the long-term treatment of pulmonary hypertension.
Sildenafil (Revatio)
Sildenafil promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in a subsequent reduction of blood pressure in pulmonary arteries and an increase in cardiac output. Sildenafil is indicated for treatment of adults and children aged 1-17 years with pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) to improve exercise ability and delay clinical worsening.
Vasodilator Agents
Class Summary
The use of vasodilators to counteract vasoconstriction in IPAH is based on both theory and on pathologic studies that implicate medial hypertrophy and vessel constriction in the pathogenesis of idiopathic pulmonary artery hypertension.
Nifedipine (Adalat CC, Procardia)
A calcium channel blocker, nifedipine inhibits calcium ion flux across the slow calcium channels, thereby inhibiting the contractile process of cardiac and vascular smooth muscle. This is most likely the mechanism by which dilation of both the systemic and pulmonary vascular beds occurs. The effect of nifedipine does not appear to be specific to the pulmonary vasculature; this agent can cause systemic hypotension. In contrast to other calcium channel blockers, nifedipine has little or no effect on cardiac conduction and little negative inotropic effect.
Nifedipine is available in oral form only. Rapid onset of action may occur with sublingual administration. The drug is also available in extended-release form.
Epoprostenol (Flolan, Veletri)
Epoprostenol (prostacyclin), a naturally occurring prostaglandin, is a potent vasodilator and inhibitor of platelet aggregation. Continuous IV infusion of epoprostenol may effect a change in pulmonary vascular resistance in patients with IPAH. Its effects are not specific to pulmonary vasculature; therefore, systemic adverse effects are common.
Use of epoprostenol is associated with tachyphylaxis. The drug is initiated at very small doses with upward titration on a regular basis.
Treprostinil (Remodulin, Tyvaso)
A prostacyclin analogue that is used to treat pulmonary arterial hypertension, treprostinil elicits direct vasodilation of pulmonary and systemic arterial vessels and inhibits platelet aggregation. The vasodilation reduces right and left ventricular afterload and increases cardiac output and stroke volume.
Treprostinil is preferably administered as a subcutaneous infusion. However, it may be administered via a central venous catheter as a continuous infusion. The injectable is FDA-approved for adolescents aged 16 years and older. Other dosage forms include oral inhalation and an oral extended-release tablet. The inhaled solution and oral tablets are FDA-approved for young adults aged 18 years or older.
Iloprost (Ventavis)
Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It is indicated for pulmonary arterial hypertension (WHO Group I) in patients with New York Heart Association (NYHA) class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.
Bosentan (Tracleer)
Bosentan is an endothelin receptor antagonist indicated for use in children aged ≥3 years with idiopathic or congenital pulmonary arterial hypertension (PAH), to improve pulmonary vascular resistance. It inhibits vessel constriction and elevation of blood pressure by competitively binding to ET-1 receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index (CI) associated with significant reduction in pulmonary artery pressure, pulmonary venous pressure, and mean right atrial pressure.
The new 32-mg tablet can be dispersed in one teaspoon of water prior to oral administration. The lower dosage and scored design enables physicians to vary the prescribed dose according to patient weight.
Because of teratogenic potential, bosentan can only be prescribed through the Tracleer Access Program (1-866-228-3546).
Ambrisentan (Letairis)
Ambrisentan is an endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with WHO class II or III symptoms. It improves exercise ability and decreases progression of clinical symptoms.
Ambrisentan inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to significant increase in cardiac index, associated with significant reduction in pulmonary artery pressure, pulmonary vascular resistance, and mean right atrial pressure.
Because of the risks of hepatic injury and teratogenic potential, ambrisentan is available only through the Letairis Education and Access Program (LEAP). Prescribers and pharmacies must register with LEAP in order to prescribe and dispense. For more information, see http://www.letairis.com or call (866) 664-LEAP (5327).
Immunological Agents
Class Summary
It is important to consider immunization with palivizumab in infants and young children with idiopathic pulmonary artery hypertension (IPAH).
Palivizumab (Synagis)
Palivizumab is a humanized monoclonal antibody directed against the F (fusion) protein of respiratory syncytial virus (RSV). Given monthly through the RSV season, it has been demonstrated to decrease chances of RSV hospitalization in premature babies who are at increased risk for severe RSV-related illness.
