Sildenafil for the Treatment of Pulmonary Hypertension in Children

Marcia L. Buck, PharmD, FCCP

Pediatr Pharm. 2004;10(2) 

In This Article

Introduction

Pulmonary hypertension, whether primary or resulting from congenital cardiac disease, remains one of the most difficult childhood diseases to treat. Currently available vasodilators, such as inhaled nitric oxide and continuous intravenous infusions of epoprostenol (prostacyclin), are limited by expense and ease of use. Sildenafil, a vasodilator developed for the treatment of erectile dysfunction, has recently been used by several investigators as an alternative to traditional therapies to dilate the pulmonary vasculature. It offers the convenience of oral dosing, has relatively few adverse effects, and costs substantially less than other agents.

Mechanism of Action

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5). Present throughout the body, PDE5 is found in high concentrations in the lungs. Inhibition of PDE5 enhances the vasodilatory effects of nitric oxide in pulmonary hypertension by preventing the degradation of cyclic guanosine monophosphate (cGMP), which promotes relaxation of vascular smooth muscle and increases blood flow. In animal models and human trials, sildenafil has been found to produce a relatively selective reduction in pulmonary artery pressure without adverse systemic hemodynamic effects. Inhibition of PDE5 by sildenafil may also enhance the platelet antiaggregatory activity of nitric oxide and inhibit thrombus formation.[1,2,3,4,5]

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