Mistica experimented with brimonidine before the release of Mirvaso. Here is what she reports:
"I would urge great caution to anyone who contemplates trying this medication.
I am a brimonidine victim. I ended up in the ER twice with the most horrific rebound flushing. I had nose bleeds, split lips and terrible flushing as the blood surged through my face looking for the weakest route. It would dart about, first engorging the side of my nose, then upper lip area, then the cheek, etc. I have seen another post here where someone else experienced this phenomenon, although in lesser form than me. I suffered permanent damage. My upper right cheek being the worst area. The vasculature continues to be excessive and very dysfunctional. Also, there seems to be nerve damage. I tried it for a couple of months in late 2010 and it is only in these last few months that it has settled down to a point, but I have to be ever vigilante. Even another attempt at IPL didn't help, but it did cause more fat loss.
The derm who told the world about brimonidine claimed none of his rosacea patients suffered rebound flushing and in fact, only benefited from the drug.
Given the fact all members here suffered rebound, that is like saying the derms patients don't require oxygen to breathe.
The mechanics of rosacea and flushing don't change, no matter which physician oversees their care.
I don't believe the claim that the rebound flushing can be prevented due to the formulation of this newly released product.
Think about it. Brimonidine is a vasoconstrictor. The body will always try and regain homeostasis.
When you tinker with receptors, no matter what they are, the body will compensate. Trying to overcome this can only be done with another type of vasconstrictor and that would just add to the problem.
Even caffeine is a vasoconstrictor. The study done on rosacea and coffee consumption was flawed, only observing the effects of heat on rosaceans.
The pathways which result in flushing are different.
Heat is obvious. Caffeine interferes with adenosine receptors, docking in them, and preventing the effects of adenosine, which is vasodilating (there are other effects). So, for a while, the face pales. But as the drug wears off, there is rebound. In addition, caffeine upregulates adenosine receptors, so when caffeine is suddenly stopped, there are excessive receptors. Withdrawal sets in. It is the same process involved with other addictions.
It is my belief that those who try this drug will initially experience relief and be so delighted with it, they will continue to use it. Then they will find they need a bit more and a bit more as break through flushing sets in. They will require more drug and the rebound will become worse and worse, until the face can't cope at all and awful rebound will set in. The damage could be permanent.
For those who aren't flushers and think they are safe, think again. If you weren't a flusher to start with, you stand a high chance of becoming one. After all, flushing is simply neurotransmitters gone out of whack.
I have tried to keep this explanation very simple so it can reach everyone with varied levels of understanding. Those who are capable can always do additional research.
Some people here are familiar with Prof Ayers, a biochemist I used to chat with. He spent a lot of time trying to shed light on the process of rosacea and flushing. When I was going through brimonidine rebound hell, I pleaded to him for help to stop the process. He said he was not able to and I just had to ride it out. He did add, that my experiment was one of the most foolish things I ever did, as the effect of brimonidine was not unexpected in his view.
And there comes the problem. Most patients don't know how drugs work. We trust those who prescribe them.
I didn't know anything about G-receptors back then. http://en.wikipedia.org/wiki/Alpha-2...ergic_receptor
Of course, it could be possible that the newly released drug is different and the scientists have found a way to overcome the problem, but I am highly suspicious they haven't. Even a dilute dose could have the same effects. I diluted mine, by the way.
Everyone needs to make up their own mind, but for those who try it, I advise a tiny test patch and not to increase that patch for several weeks. Just in case.
By the way, clonidine is similar. That causes rebound too." Mistica 4th September 2013 01:04 AM Post #70
Just to remind you, in case you missed it in my post, I was examined by an immunologist at the time of my severe rebound and no allergy was found. I had tryptase, histamine and all the IgA, IgG, IgE, etc tested and they were all normal. The doctor was looking for mastocytosis as well, and seemed to be rather disappointed that my levels were not suggestive of this.
Now, to be fair I do have other health issues, but they are not related to allergy.
I was already a bad flusher, but it had become significantly better in some ways over the preceding year or so.
How rebound worked in me.
I had a very pink baseline redness all over my face with much redder cheeks, nose. I had to be very vigilante with my diet and environment and still relied heavily on ice packs to control flushing, but with this preventive regime, my flushing was definitely downgraded to what it had been.
When I first applied brimonidine, it paled me unnaturally, but at the same time, the visible vessels appeared to be more prominent against their ghostly background.
From memory, I spent the first day test driving it around the house.
Then I decided to go out. First to the dentist and then the mall.
I was pretty stunned to experience a fairly small, but intense area of flushing on my upper right cheek.
The area became very hot and deepened in colour.
It looked unnatural, as if I had painted it on with marked borders.
We left the dentist and walked around the mall. After some time the area completely vanished.
I rinsed my face when I came home and went to bed. By morning, my face was fully reddish again, but no worse, as far as I recall.
The pattern thereafter was the same type of 'break through' intense vasodilation. It would appear in one area, disappear and then appear elsewhere, such as in the middle of my upper lip area. It would again, be really intense. (That pattern is not indicative of any type of allergy).
Then I would be worse by morning.
At the time, I had to attend several dental appointments and because the air conditioning was not working properly in the clinic, I foolishly relied on brimonidine to get me through the appointments, thinking, just one more day, etc. Big mistake.
I was much worse every morning and my severe flushing was returning.
I tried quitting cold turkey, but that made me much worse and then I began another foolish experiment of gradually diluting the drug, more and more. But it did not work and I got stuck in a vicious cycle of calming and intense flushing.
After application my face did pale, but the 'break through' flushing was occurring more and more and in the end you could see it happening. It was as if a mole were burrowing under my skin, travelling through the plumbing at high speed. Coming out here and there randomly. I noted another poster comment on this weird pattern of flushing. When the inside of my right ear started to flush, it became very painful.
My upper cheeks especially the right suffered the most. To this day, it is a vascular mess.
In the end, the brimonidine didn't work at all. It was as if the receptors it was influencing, completely dysfunctioned. The final application had the opposite effect. It caused extreme flushing. Of course a scientist could give you a run down of likely biochemical reactions. My layperson's report is brimonidine caused a raging, flushing inferno, and it was one hellacious ride I wished I had never embarked upon.
I ended up in the ER twice, as I have previously mentioned as the break through flushing was so intense, my nose bled and my lips split. I did not receive any useful help, and of course in retrospect I wished I had not gone there either, as the awful lights and stress just amplified the reaction and flushing.
I was given one dose of prednisone during my second visit and they only served to make me much worse!
Of course, the stress all this caused just made the flushing much worse still! I couldn't sleep as each time I lay back on my pile of pillows and started to drift off to sleep, it was as if the final brace holding back the build up of flushing, broke down and the blood raged through the veins in a torrent!. I was so painful! I cried in pain. Ice packs did not help at that point and of course, you have to be careful with icing. It is an art.
I started to stay awake most of the night due to the pain and flushing. Lack of sleep worsens flushing, so this was just another nail in the coffin, so to speak. This continued for weeks.
In the end, I fell asleep out of exhaustion and the flushing raged all night, for several nights.
Then it stopped. Well, the intensity stopped, but I was left with damage. I was, again, a severe flusher. It took some weeks for the earache to subside. My doctor told me the canal was inflamed and then peeled.
The original area of breakthrough flushing on my upper right cheek, extended it's borders to encompass a much larger area and it remains today. I have even had IPL, which did not help much. The upper cheek suffered some kind of nerve damage. I expect that is not the right word, 'damage' as it is not numb, but it can hurt, a type of feeling that drives me crazy. A dull, sickening feeling much like hitting your elbow.
I am happy to say, that these days, the nerve pain/sensation has reduced a lot and I can go months without it being present.
The area is still highly vascularised however.
I am an extreme case, and it was made much worse by my foolish decision to try and wean myself off the drug over time with gradual dilutions.
I suppose the only good thing to come of my horrendous adventure is an insight to what might happen to others should they decide to continue use of brimonidine.
I can not emphasize enough what a big mistake it is to try and reduce vascular symptoms with this drug.
I hope this long post helps clarify what I mean by rebound flushing. I can only equate it to holding a garden hose, the pressure builds up, and when you release the end, a torrent pumps out.
Of course the hose flow quickly returns to it's previous state, where as the face does not." Mistica November 19, 2013 Post #850