Current PAH guidelines describe 3 available pathways to treat this progressive disease1,2
Nitric Oxide (NO) |
PDE-5i Therapies and sGC Stimulators: |
Endothelin |
ERA Therapies: |
Prostacyclin |
Prostacyclin-class Therapies: |
cGMP=cyclic guanosine monophosphate; ERA=endothelin receptor antagonist; PAH=pulmonary arterial hypertension; PDE-5=phosphodiesterase type 5; PDE-5i=phosphodiesterase type 5 inhibitor; sGC=soluble guanylate cyclase.
Prostacyclin is essential to normal lung function. Produced by pulmonary endothelial cells, prostacyclin has effects directed toward the local pulmonary vascular wall and blood cells. Patients with PAH may have low levels of prostacyclin.3,4
Prostacyclin analogs act on multiple receptors2,5-9*
*EP4 and FP receptors are not represented in figure. Receptor pathways simplified for illustrative purposes.
cAMP=cyclic adenosine monophosphate; DP=prostaglandin D2 receptor; EP=prostaglandin E2 receptor; FP=prostaglandin F receptor; IP=prostaglandin I2 receptor; TP=thromboxane prostanoid receptor.
Learn more about a prostacyclin analog treatment option
TREATMENT OPTIONSReferences: 1. Galiè N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 suppl):D60-D72. 2. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436. 3. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159(6):1925-1932. 4. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary hypertension. Eur Respir J. 2008;31(4):891-901. 5. Clapp LH, Gurung R. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 2015;120:56-71. 6. Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and activity of the prostacyclin receptor (IP) agonist, treprostinil and iloprost, at human prostanoid receptors: treprostinil is a potent DP1 and EP2 agonist. Biochem Pharmacol. 2012;84(1):68-75. 7. Falcetti E, Flavell DM, Staels B, Tinker A, Haworth SG, Clapp LH. IP receptor-dependent activation of PPARγ by stable prostacyclin analogues. Biochem Biophys Res Commun. 2007;360(4):821-827. 8. Bishop-Bailey D. Peroxisome proliferator-activated receptors in the cardiovascular system. Br J Pharmacol. 2000;129(5):823-834. 9. Kohyama T, Liu X, Kim HJ, et al. Prostacyclin analogs inhibit fibroblast migration. Am J Physiol Lung Cell Mol Physiol. 2002;283(2):L428-L432.