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Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin\u20101 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin\u20101 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in\u2010depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.<\/jats:p>","DOI":"10.1002\/j.1875-9114.2012.01114.x","type":"journal-article","created":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T08:25:48Z","timestamp":1346747148000},"page":"838-855","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Practical Considerations for the Pharmacotherapy of Pulmonary Arterial Hypertension"],"prefix":"10.1002","volume":"32","author":[{"given":"Bryan M.","family":"Bishop","sequence":"first","affiliation":[{"name":"Colleges of Pharmacy and Pharmaceutical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent F.","family":"Mauro","sequence":"additional","affiliation":[{"name":"Colleges of Pharmacy and Pharmaceutical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samer J.","family":"Khouri","sequence":"additional","affiliation":[{"name":"College of Medicine The University of Toledo Toledo Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp297"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-2-216"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-5-343"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.503540"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4901.102568"},{"volume-title":"Primary pulmonary hypertension: executive summary from the world symposium on primary pulmonary hypertension","year":"1998","author":"Rich S","key":"e_1_2_7_9_1"},{"key":"e_1_2_7_10_1","first-page":"1883","volume-title":"Pulmonary hypertension","author":"Rich S","year":"2008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2006.11.010"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000156326.48823.55"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035488"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.01.004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2006.12.003"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199207093270203"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.76.1.135"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309093291117"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.87.2.265"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.83.4.708"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.126.1_suppl.35S"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2674"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.75.2.171"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-99-4-433"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.488486"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-112-7-485"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-121-6-199409150-00003"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340504"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.2.9906015"},{"volume-title":"Flolan (epoprostenol) package insert","year":"2008","author":"GlaxoSmithKline","key":"e_1_2_7_30_1"},{"volume-title":"Veletri (epoprostenol)","year":"2010","author":"Actelion Pharmaceuticals US Inc","key":"e_1_2_7_31_1"},{"volume-title":"Redbook \u2122 for Windows\u00ae [intranet database]. 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