Leading expert in pulmonary hypertension explains phosphodiesterase 5 inhibitors use in PAH therapy. Sildenafil and tadalafil. Pulmonary arterial hypertension treatment. Dr. Anton Titov, MD. You mentioned phosphodiesterase type 5 inhibitors. They are also used for erectile disfunction. Common medications are Viagra, (sildenafil), Cialis (tadalafil). There are other medications of that class. These medications are also used to treat pulmonary arterial hypertension. How phosphodiesterase type 5 inhibitors are used for pulmonary arterial hypertension therapy? Dr. Anton Titov, MD. Are they effective? Dr. Anton Titov, MD. Dr. Aaron Waxman, MD. There is probably a different dosing schedule. Phosphodiesterase 5 inhibitors are in the nitric oxide pathway. Nitric oxide response is our most potent vasodilator. It works through cyclic GMP. All the phosphodiesterase 5 inhibitors do is keep that cyclic GMP around longer by preventing its breakdown. Dr. Aaron Waxman, MD. Within the same pharmaceutical path now we also have a medication called Riociguat (Adempas). It is a soluble guanylate cyclase stimulator. It increases the amount of available cyclic GMP. Riociguat (Adempas) works in parallel with nitric oxide. Riociguat (Adempas) also works independently of nitric oxide in pulmonary arterial hypertension. Patients with pulmonary arterial hypertension generally have inadequate nitric oxide production. Dr. Aaron Waxman, MD. All of these medications are vasodilators. There is probably some added benefit of vasodilation in pulmonary arterial hypertension. Although we don't fully understand yet how. There is a cellular remodeling in pulmonary arterial hypertension. It is both myocardial remodeling and vascular remodeling. But there is no way to know which patients are going to get the most benefit from each individual medication. But I would say from an efficacy standpoint they are all pretty equivalent in pulmonary arterial hypertension. Dr. Aaron Waxman, MD. We don't combine these medications. But as individual medications sildenafil, tadalafil, riociguat are all pretty equivalent. Sildenafil, tadalafil, riociguat in pulmonary arterial hypertension treatment. Are they used early in a therapy of pulmonary arterial hypertension? Dr. Anton Titov, MD. Or they are used when the first line of therapy fails? Dr. Anton Titov, MD. Dr. Aaron Waxman, MD. No, they probably are now first line therapy. Certainly sildenafil and tadalafil are considered first-line therapy. Because they are generally very well tolerated. Sildenafil and tadalafil are easy to use. They have been around for a long time in pulmonary arterial hypertension. Riociguat is a little more complicated to use because there is titration involved. It has a little more broader FDA approval targeting. Indication for use of Riociguat (Adempas) includes chronic thromboembolic disease. But otherwise it is probably equally effective in pulmonary arterial hypertension. What is a typical dose of tadalafil and sildenafil in pulmonary arterial hypertension? Dr. Anton Titov, MD. Is it a smaller dose compared with doses used for erectile dysfunction indications? Dr. Anton Titov, MD. Dr. Aaron Waxman, MD. We did the clinical trials in pulmonary arterial hypertension. We studied sildenafil at 20 milligrams, 40 milligrams and 80 milligrams, at 3 times per day. The usual dose of sildenafil for erectile dysfunction is 25, 50, 75 mg, and a 100 mg, "when you need it". Certainly during the clinical trial, we were using Viagra at those doses. It was before Viagra was approved for pulmonary arterial hypertension. There is room for dose adjustment. The only dose of sildenafil that was approved was 20 milligrams three times a day. Dr. Aaron Waxman, MD. From an insurance standpoint we might have a little difficulty changing dose. But we often do titrate the dose. We used tadalafil (Cialis) at 40 milligrams once a day for treatment of pulmonary arterial hypertension. Every day? Dr. Anton Titov, MD. This is a frequent and fairly large dosing for pulmonary arterial hypertension treatment. What were the cardiovascular side effects of tadalafil and sildenafil? Dr. Anton Titov, MD. What other side effects have you seen in treatment of pulmonary arterial hypertension? Dr. Anton Titov, MD. It is interesting. Dr. Aaron Waxman, MD. The reason we went to phosphodiesterase inhibitors medications is this. Phosphodiesterase 5 is predominantly localized to the vessels of the lung and the vessels of the penis. We don't see a huge incidence of cardiovascular side effects. There are some patients whose blood pressure may be a little low with these medications. But most patients with pulmonary arterial hypertension tolerate sildenafil and tadalafil quite well. The most important side effect that we see is headache. Dr. Aaron Waxman, MD. But it is not a bad headache. But it can be a nuisance. But headache from sildenafil or tadalafil is usually readily responsive to Tylenol and aspirin. Or other non-steroidal anti-inflammatory medications.