title: Therapeutic approaches to pulmonary hypertension in hemoglobinopathies: Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathy.
abstract: New approaches to the treatment of pulmonary arterial hypertension (PH) have increased symptomatic relief and prolonged survival. PH is a common sequela of the hemoglobinopathies, but the use of standard oral treatment options is limited because of toxicity and poor effectiveness. Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5), which promotes selective smooth muscle relaxation in lung vasculature and has been used successfully in the treatment of PH. Hemoglobinopathic patients suffering from severe PH who were treated with sildenafil citrate (50 mg b.i.d.) for periods ranging from 4 to 48 months showed a significant decrease in pulmonary pressure and improvement in exercise capacity and functional class. No significant adverse events were reported. These data, described in a small group of patients, indicate that sildenafil citrate is effective in the treatment of PH in hemoglobinopathies and is well tolerated long-term at a daily dose of 100 mg.
authors.affiliation: Struttura Complessa di Cardiologia, Centro della Microcitemia e delle Anemie Congenite, Ente Ospedaliero Ospedali Galliera, via Volta 8, 16128 Genoa, Italy. giorgio.egildo.derchi@galliera.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Derchi
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004341:Drug Evaluation; D017079:Exercise Tolerance; D006453:Hemoglobinopathies / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D000860:Hypoxia / Q000209:etiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human