iloprost and fasudil

This paper provides an overview of the current state of pharmacotherapy in children with pulmonary arterial hypertension (PAH) and a brief introduction to the potentially novel pharmacologic targets for PAH. Currently, 3 classes of drugs including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase-5 inhibitors are approved for the treatment of PAH in children, which has led to improved hemodynamics, increased exercise capacity and prolonged survival. Despite these improvements, there is still a need to carry out well-designed, randomized, controlled studies with larger samples. In addition, novel drugs targeting other molecular pathways should be developed.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Bosentan; Calcium Channel Blockers; Child; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Iloprost; Sulfonamides

The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH).. Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.. Comparable decreases were observed in mean pulmonary artery pressure (-4.6 ± 4.3 mmHg vs. -4.8 ± 4.2 mmHg) and pulmonary vascular resistance (-3.0 ± 3.0 Wood U vs. -2.2 ± 2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7 ± 17.1% vs. 6.9 ± 15.0%; p=0.044 and 4.5 ± 5.3% vs. 2.7 ± 8.2%; p=0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8 ± 3.6%), infused fasudil resulted in a non-significant reduction (-0.6 ± 1.1%).. Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Administration, Inhalation; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vasodilator Agents; Young Adult