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Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e
| Section IV. Inflammation, Immunomodulation, and Hematopoiesis > |
Pharmacotherapy of Pulmonary Arterial Hypertension
Sections: Prostacyclin, Endothelin Receptor Antagonists, Phosphodiesterase 5 Inhibitors, Sildenafil, Tadalafil.
Topics Discussed: ambrisentan; anti-asthmatic agents; asthma; bosentan; endothelin receptor antagonists; epoprostenol; lung diseases; pharmacotherapy of respiratory disorders; phosphodiesterase-5 inhibitors; primary pulmonary hypertension; pulmonary arterial hypertension; pulmonary vasodilators; secondary pulmonary hypertension; sildenafil; tadalafil; vasodilators.
Excerpt:"Pulmonary arterial hypertension (PAH) is characterized by vascular proliferation and remodeling of small pulmonary arteries, resulting in a progressive increase in pulmonary vascular resistance, which may lead to right heart failure and death (Morrell et al., 2009). PAH involves dysfunction of pulmonary vascular endothelial and smooth muscle cells and their interplay and results from an imbalance in vasoconstrictor and vasodilator mediators.Prostacyclin (PGI2; Epoprostenol) is produced by endothelial cells in the pulmonary circulation and directly relaxes pulmonary vascular smooth muscle cells by increasing intracellular cyclic AMP concentrations (see Chapter 33). Reduced prostacyclin production in PAH has led to the therapeutic use of epoprostenol and other stable prostacyclin derivatives (Gomberg-Maitland and Olschewski, 2008). Functionally and physiologically, PGI2 opposes the effects of TXA2.Sildenafil (REVATIO) is a selective PDE5 inhibitor that is given at a dose (20 mg three time daily orally) that is lower than used for erectile dysfunction (100 mg; Chapter 27). It is effective in lowering pulmonary resistance and improving exercise tolerance in patients with PAH. Side effects include headache,..."
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