Sildenafil

Sildenafil (Viagra, Revatio), epoprostenol (Flolan), bosentan (Tracleer) and sitaxentan (Thelin) are licensed for the treatment of pulmonary hypertension.Epoprostenol is the only one available for intravenous use. Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), the enzyme that is responsible for degradation of cGMP. Apart from the presence of this enzyme in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells, resulting in relaxation. In patients with pulmonary arterial hypertension this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.

Uses
Pulmonary hypertension

Contraindications
Recent stroke or MI
Severe hypotension (SBP < 90mmHg)
Severe hepatic impairment (Child-Pugh class C)
Avoid concomitant use of nitrates, ketoconazole, itraconazole and ritonavir

Administration
• Orally: 20 mg 8 hourly
   Renal impairment: 20 mg 12 hourly
   Hepatic impairment (Child-Pugh class A and B): 20 mg 12 hourly

Adverse effects
GI disturbances
Dry mouth
Flushing
Headaches
Back and limb pain
Visual disturbances
Hearing loss
Pyrexia

Cautions
Hypotension (avoid if SBP < 90mmHg)
Dehydration
Left ventricular outflow obstruction
IHD
Predisposition to priapism
Bleeding disorders
Active peptic ulceration
Hepatic impairment (avoid if severe)
Renal impairment (reduce dose)