Clinical use of PAH drugs based on functional class Clinical use of PAH drugs based on functional class. Treatment of PAH is generally based on the patient’s functional classification at the time of presentation. Four functional classes have been defined for PAH: (I) no symptoms or functional limitation; (II) slight limitation of physical activity; (III) marked limitation of physical activity; and (IV) symptoms with any activity or at rest. In patients with no functional limitation, there is no specific therapy that has shown benefit in clinical trials. Expert guidelines recommend only supportive care and physical rehabilitation in this group. Patients with symptoms consistent with functional classes II and III have the best evidence for therapeutic benefits. First-line therapeutics include oral agents such as ERAs, PDE5 inhibitors, sGC stimulators, and the IPR antagonist selexipag. Inhaled PGI2 analogues can also be considered. The oral formulation of treprostinil has been approved for use in minimally symptomatic individuals but should be reserved for use only as monotherapy. The most severely limited patients, those in functional class IV, or those with evidence of right heart dysfunction should be started on the most potent vasodilators, which include the intravenous and subcutaneous formulations of PGI2 analogues. Alternatively, combination therapy using multiple agents has been shown to be effective in small clinical trials and one phase 3 clinical trial combining ambrisentan and tadalafil. *approved for monotherapy only. Source: Treatment of Pulmonary Arterial Hypertension, Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e Citation: Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e; 2017 Available at: https://accessmedicine.mhmedical.com/DownloadImage.aspx?image=/data/books/2189/goodman13_ch31_f002.png&sec=170107264&BookID=2189&ChapterSecID=170107240&imagename= Accessed: November 11, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved