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Exclusive interview / Dr. Anton Titov MD and Professor Dr. Aaron Waxman MD, leading pulmonary arterial hypertension, right heart failure and lung disease expert. Find out exact cause if you have shortness of breath - get a precise diagnosis and best treatment for shortness of breath root cause.
- Pulmonary arterial hypertension treatment. You mentioned phosphodiesterase type 5 inhibitors. They are also used for erectile disfunction. Common medications are viagra, sildenafil, and there are other medications of that class. So they're also used to treat pulmonary arterial hypertension. What is a typical way how they are used for pulmonary arterial hypertension? Are they effective? There is probably a different dosing schedule of those medications? So phosphodiesterase 5 inhibitors are in the nitric oxide pathway. And nitric oxide response, which really is our most potent vasodilator, works through cyclic GMP. So all the phosphodiesterase 5 inhibitors do is keep that cyclic GMP around longer by preventing its breakdown. And within the same path now we also have a medication called Riociguat, which is a soluble guanylate cyclase stimulator. So it actually increases the amount of available cyclic GMP and works in parallel with nitric oxide or independently of nitric oxide in pulmonary arterial hypertension. These patients generally have inadequate NO production. So all of these drugs are vasodilators. There's probably some added benefit, although we don't fully understand yet how, as far as remodeling - both myocardial remodeling and vascular remodeling. But there's no way to know which patients are going to get the most benefit from each individual drug. But I would say from an efficacy standpoint they're all pretty equivalent in pulmonary arterial hypertension. We don't combine them, but as individual drugs they're all pretty equivalent.
- Are they used early in a therapy of pulmonary arterial hypertension, or when the first line therapy fails?
- No, they probably are now first line therapy. Certainly sildenafil and tadalafil are considered first-line therapy, because they're generally very well tolerated and they're easy to use and they've been around for a long time in pulmonary arterial hypertension. I think Riociguatis a little more complicated to use because there's titration involved and it has a little more broader FDA approval targeting. It includes chronic thromboembolic disease but otherwise it's probably equally effective in pulmonary arterial hypertension.
- Is the typical dosage [of PDE5 inhibitors in PAH] continuous or daily? Is it a smaller dose to compare with doses used for erectile disfunction indications?
- When 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. So the usual dose for erectile dysfunction is 25, 50 and 75 mg, and a 100 mg, "when you need it". So certainly during the clinical trial, before the drug was approved, we were using Viagra at those doses. So I think there's room for dose adjustment. The only dose that was approved was 20 milligrams three times a day. So from an insurance standpoint we might have a little difficulty changing dose. But we often do titrate the dose, and Tadalafilwe use it at 40 milligrams once a day.
- Every day? So with this frequent and fairly large dosing for pulmonary arterial hypertension treatment, as far as the cardiovascular side effects or other side effects, have you seen any major side effects? It's interesting, because the reason we went to these drugs are because phosphodiesterase 5 is predominantly localized to the vessels of the lung and the vessels of the penis. So we actually don't see a huge incidence of cardiovascular side effects. There are some patients whose blood pressure may be a little soft [low] with these drugs. But most patients with pulmonary arterial hypertension tolerate it quite well. I think the most important side effect that we see is headache, and it's not a bad headache. But it can be a nuisance. But it's usually readily responsive to simple things like Tylenol and aspirin or a non-steroidal anti-inflammatory medications.
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