You’ll go blind! so the joke goes. It turns out that Viagra, Cialis etc… are alleged to be involved with vision loss in some patients which is something that we predicted might happen a few years ago. My wife told me this morning that this issue is finally starting to make it around to the popular media, but I first heard about this possibility several years ago when my mentor and I were talking about phototransduction and phosphodiesterase inhibitors.
The mechanism for vision loss that everyone is talking about is called non-arteritic anterior ischemic optic neuropathy and can occur in men who have diabetes or heart disease, which are two conditions that typically can lead to impotence and therefore may cause these same patients to seek out assistance. This of course is why drugs like this are prescription drugs and should be carefully monitored and administered by physicians.
However, this form of blindness is not what I am concerned about and I think these are two separate issues that perhaps are being missed by the community as a whole. Viagra, Cialis and Levitra are “selective” phosphodiesterase inhibitors. I put that in quotes, because they apparently are not that selective and have some degree of overlap with another phosophodiesterase involved in vision. Specifically, there is a 10:1 selectivity ratio for PDE-5 over that of the closely related PDE-6 enzyme that we will get to in a minute. So the intended mechanism for these drugs is: Sexual arousal leads to increased parasympathetic activity which results in production of nitric oxide (NO). NO activates the enzyme guanylate cyclase which increases cGMP concentrations. cGMP acts by dilating the smooth muscles in blood vessels which results in increased blood flow and…..enlargement. Normally, cGMP is then degraded by the enzyme phosphodiesterase5 (PDE-5) and in the absence of maintained NO synthesis, vasodilation is reduced, reversing the whole process. These drugs work on PDE-5, preventing its inactivation which results in a prolonged activity of PDE-5 and therefore, prolonged vasodilation. The problem is with this lack of selectivity issue. As discussed above, these drugs also inhibit a closely related phosophodiesterase enzyme, phosphodiesterase6 (PDE-6) which is found in the retina and plays an important role in the normal visual transduction cascade.
In vision, cGMP will keep Na+ channels open in the membranes of your photoreceptors. Photons when they hit the photoreceptors, are absorbed by another molecule called 11-cis retinal which causes a conformational change to a trans retinal form. Activated rhodopsin at this point catalyzes the conversion of GDP to GTP which then activates the transducin protein. Transducin contains multiple subunits including an alpha subunit which breaks off when activated. The activated alpha subunit breaks away from the beta and gamma subunits of transducin and then “pulls away” the inhibitor from PDE-6. At this point PDE-6 then converts cGMP to 5′GMP whereupon the reduced cGMP levels allow for Na+ channel closure. If Viagra inhibits PDE-6, the channels in photoreceptors are constitutively open which means they never shut down.
This explanation over coffee this morning Led my wife, H to quip: “wow, so you pop a rod and you pop rods!”, which was not entirely true, but it was sufficiently funny for me to almost launch my latte out of my nose.
Seriously though, there are certainly visual alterations reported with the use of these drugs including vision with a blue tint, difficulty distinguishing between blue and green light and light sensitivity. In fact, pilots are prohibited by the FAA from flying within 12 hours of using Viagra. These of course are short term problems, but there are issues that should cause some concern. Notably, there are defects in PDE subunits that are associated with a form of retinal degeneration called retinitis pigmentosa or RP (the group of diseases that much of my doctoral dissertation was about). Additionally, there are defects in the cGMP gated cation channels that are also associated with RP. If the biology and pharmacology of these drugs mimic the issues that are functionally related to aberrant activity of these diseased proteins, then we may have a problem.
Thank you for the post. You’ve provided more info than I could get from the manufacturer, pharmacist, and doctor. Of course my pharmacist and doctor are limited to what info they get from the manufacturer as well. I’ve very much wanted to try this class of drug for my own ED. I’m only 50 and would like to remain sexually active. Unfortunately I have RP, am “legally blind” and still haven’t been able to get an accurate risk/benefit estimation. If you have any more info on this issue I’d like to get it to my doctor to follow up.
Thank you for the comment Mike.
First off, I should note that I am a research scientist and not a physician and that any information on my blog entry should not necessarily be construed as clinically relevant, or medical advice, especially as it is not my area of expertise. Furthermore, it is pure conjecture based on my understanding of the molecular processes of phosphodiesterase and the isoforms of PDE in retina. However that said, I stand by what is written there.
Unfortunately, I have not really followed the literature since writing that blog entry (dated 2005) and cannot advise on the issue other than to say that after spending a couple of hours in a literature search this evening, I find nothing new on the issue and in fact, some disagreement over the actual effects of ED drugs on the photoreceptors. I cannot really say whether or not Viagra and other ED drugs have an effect on or accelerates retinal degeneration as I have not done those studies, but have been thinking of actually starting a small investigative study. I suspect that like anything taken in moderation it would be OK, but I should leave that decision up to you and your physician.
Our work in RP has been focused on characterizing what happens to the retina during the disease process and most recently, we are involved in developing and testing some new drugs that we hope will have some efficacy in limiting retinal cell death in both RP and AMD. An appropriate assay of drugs is somewhat dependent upon developing new models of RP and that is another effort that is just about to pay off.
Right now however… science funding is under intense competition for limited resources and as such, we do not have any current treatments to delay or reverse the changes in the retina. But we are passionate and working very hard on curing blindness.
If you have any more information on RP and Viagra, plese post it here, been looking for, and not finding much help, what a horrible thing to have to choose between, what a cruel fate, lol! If you could post any web sites on the subject it would be greatly appreciated.
Thanks so much…
I will absolutely post information here if I run into it. I don’t necessarily think that it is a huge risk, but like most things in life, things done in moderation likely will not hurt you.
Hey thanks to you all particularly B W Jones for your research into RP (I have RP) I also have ED and have been prescribed Viagra by my doctor. He obviously forgot I had RP or didn’t read who shouldn’t be prescribed Viagra as it says clearly on the information enclosed that RP sufferers should not take it. That is obviously Pfizer covering for their lack of research into this possible problem with their product & RP sufferers. I will keep an eye (no pun intended) on this blog & hope to read more if and when it is available. Take care, Shane, Navan, Ireland.
Hey Shane, does the insert really contraindicate viagra for people with RP? That would be new and very interesting.
I’ll absolutely keep this updated with anything new I learn or hear.
Best regards,
Hi what are your thoughts on the findings in this test? http://abstracts.iovs.org/cgi/content/abstract/44/5/3563
It appears when tested on mice there was no evidence to show Viagra affects RP sufferers. Or is this just wishful thinking?
Hey Steve,
Yeah, I’ve seen that study and while I respect the results, it was a very short term study (~48hrs) while the effects on retinal degeneration take years. As I said, any short term usage is probably just fine, but I worry about longer term implications.
If your hypothesis is correct, the common pathway for all RPs resulting in vision loss should be PDE 6. If all RPs have subnormal PDE6 , then you have hit the big jackpot. Because theoretically by reverse bioengineering, PDE6 can be artificially synthesized or drugs to block the breakdown of PDE6 can be research.
Hey Edmund,
Thanks for the comment. Actually, there are many, many causes of RP, only a certain percentage of which have defects in the PDE pathways. Other forms of RP are caused by mis-trafficked rhodopsin or by defects in the retinal pigment epithelium cells or by packing abnormalities of opsins in the photoreceptors. So, a single “silver bullet” is not going to solve all instances of RP.
Thanks for the post. It was a good review for me after optometry school. I definitely enjoyed your wife’s comment. I have a patient asking about vision and viagra. Any good resources for NAION and viagra?
AAO actually has a decent page: http://eyewiki.aao.org/Non-Arteritic_Anterior_Ischemic_Optic_Neuropathy_(NAION)