cGMP-specific phosphodiesterase type 5

And then you have drugs that work on the nitric oxide pathway.

These are all PDE5 inhibitors, like the sidenafil and tidalafil, plus drugs like riosiguat, which is going to stimulate the guanylate cyclase directly.

If you need help with some of these drug names, make sure you look at the study sheet that's uploaded into the Atomic Anesthesia Platform, and that's going to go through all of these in more detail.

Now, a small number of patients who respond to vasodilator testing are also treated with calcium channel blockers.

Now, sidenafil or Viagra is going to block phosphodiesterase type 5.

That's the enzyme that's going to break down cyclic GMP.

Now, PDE5 is pretty plentiful in the pulmonary circulation, so sidenafil is going to act relatively selectively on the PBR.

It can also enhance the inhaled nitric oxide and help blunt any kind of rebound when you start to wean that off.

The AUA specifically states that testosterone therapy alone is not an effective treatment for erectile dysfunction.

For men who have both confirmed testosterone deficiency and ED, testosterone treatment may be considered alongside established erectile dysfunction treatments, such as phosphodiesterase type 5 or PDE5 inhibitors, the medication class that includes sildenafil and tidalafil.

The guideline notes that these medications may be more effective when combined with testosterone therapy in men who have both conditions, although the evidence supporting that recommendation is less robust than some of the stronger diagnostic recommendations.

So if a man is experiencing erectile dysfunction, simply starting testosterone without evaluating the other possible causes may leave an important part of the problem unaddressed.

But depending on the patient subtype, like an ILD patient may be able to transition to another inhaled agent that they can actually leave the hospital on, like inhaled treprostanil, which there's a couple of trade name formations of that now, formulations of that.

And then in the COPD case, that's much less clear what you would do, how you would get them, you know, what would be the next step because You know, if they have very severe pH, some people may try like PDE5 inhibitors like sildenafil or tildalafil as a transition plan.

But if you're just using it in the acute setting for a chronic problem, you have to say, what's my endpoint?

Sure.

in that patient who's still at intermediate low risk.

And there was one trial, it was randomized, but open label, looking at the switch from PDE5s to riosiguat.

So those are also options in that patient population.

And You know, this is really where that whole shared decision-making comes into place.

Poppers donate that nitric oxide.

And so when you mix poppers and PDE5 inhibitors, you actually get much more of an effect.

And there can be particularly severe interactions.

PDE5 isn't specific to the penis.

It's found across the body.

And so there can be profound vasodilation across the body.

And so mixing poppers and PDE5 inhibitors can actually lead to a more significant toxicity.

And what's interesting, of course, is...

I think it's an interesting study.

I had a conversation with a colleague of mine, actually Dr. Sam Ward, he practices in Belgium, and he had a similar experience with his patient population where it seems like people need to be on a PDE5 inhibitor in combination with Botox for it to actually work.

which I think is very important.

Oftentimes we're trying to figure out is PRP, Botox, whatever the newest and greatest formulation is, is that alone going to lead to benefit? And the reality is we get the most benefit when we oftentimes combine these novel therapeutics with things we already have on the market.

And if they just sectioned out the men who did, They got much better results.

Yeah.

So I'd say what I learned from this article and how I would take this into my clinical practice is if I had a patient who wanted to have Botox injected into his penis for erectile function, I would highly recommend he take a PDE5 inhibitor at the same time and probably just a daily Cialis versus just an on-demand sildenafil.

Yeah, I agree with that.

So those are just five of quick ones on the supplements.

Five of the small molecules, baby aspirin twice a day, colchicine, um, a statin, whether you need it or not, for LDL lowering, um, a, uh, PDE5 inhibitor, and, um, a, uh, GLP-1.

So those are all, um, have more benefit than risk even when not for the purpose for which they were approved by the FDA, um, for the average 50-year-old man and woman.

And, and as we always say on the show, um, you don't do anything I say without checking with your doc personally.

What is it designed to do? Is it a vasodilator of sorts?

So they work in different mechanisms, but similar to the medications that we have, PDE5 inhibitors.

PDE5 inhibitors work in the erection cascade.

Basically what happens...

Actually, let's take it back to the nitric oxide thing and we'll get there.

Cause again, and we should probably get back to this, you know, um, you know, some people will have sex for long periods of time, some for shorter periods of time.

And here people don't really know what other people are doing except by way of pornography and self report and discussion.

So, um, Is it the case that drugs that increase dopamine can inhibit the sexual response? Do they tend to promote the sexual response? Because I also mentioned earlier, there's this growing trend of people taking, by way of prescription, of course, from a physician, combined apomorphine, which is a dopaminergic drug, with tadalafil, which is a PDE5 inhibitor, so it's gonna increase blood flow.