Propranolol And Norepinephrine Reuptake?

[~elizabeth~]

Before my POTS diagnosis, I was seeing a dermatologist who started me on clonidine, and then tried adding other drugs to try to control my painful flushing. He tried 2 betablockers (atenolol and labetolol) but they both made things much worse, and I stopped them immediately.

Recently my GP suggested trying propranolol (inaddition to clonidine) to try to control the problems. This time I monitored things a little more closely. I'd already begun to suspect I might have Raynaud's in my face, I'd had a bad bout of facial pain after trying nortripytline (by pain I mean pins and needles/numbness sensations). The nortripytline raised my BP a lot, presumably because it acts as an NRI, which negated some of the effects of the clonidine on lowering BP.

After starting the propranolol, I noticed that it was having some of the same effects as the nortripytline. My blood pressure had been low on clonidine alone (80/50 ish) but went up to 115/90 ish, and the facial dysaesthesias were also bad. I found some references to reports of clonidine and propranolol paradoxically causes a rise in BP, also that propranolol, can actually cause catecholemines/BP to rise when given to control severe hypertension during clonidine withdrawal.

Given that it seemed to have the same effect on me as nortripytline, my hunch is that propranolol somehow actually raises norepinephrine levels. On the propranolol wikipedia page it says:

"Research has also shown that propranolol has inhibitory effects on the norepinephrine transporterand/or stimulates norepinephrine release (present experiments have shown that the concentration of norepinephrine is increased in the synapse but do not have the ability to discern which effect is taking place).^[27] Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenergic activation, with the α1-adrenoceptor being particularly important for effects observed in animal models. Therefore, some have suggested that it be looked upon as an indirect α1 agonist as well as a β antagonist."

http://en.wikipedia.org/wiki/Propranolol

[bustersacc11]

I have taken a centrally-acting sympathomimetics, Methyldopa which doesn't have the rebound hypertension issue like clonidine, and propranolol at the same time briefly. Centrally-acting sympathomimetics(works up in the brain area) reduces sympathetic outflow so from my experience symptoms calmed down and lowered norepinephrine levels. While propranolol just blocked the effects of adrenaline. So, your third paragraph reference makes sense to me (not a dr). As you are weening off clondine you are potentially opening up those adrenaline flood gates again since the two drugs mechanism of action are different. Even though you are blocking the attachment of the adrenaline to the receptors that affect the heart you're not necessarily always lowering your norepinephrine levels. Way I understand it and could be wrong.

The last paragraph. Suggesting the possibility that it has a Midodrine effect, while blocking adrenaline to beta receptors on the heart and periphery. Interesting. You are having controlled blood pressure with Clonidine alone but since you added another blood pressure med to the mix your pressures rise is interesting. I understand going from 80/50 to 110/90 that you feel a difference while those are still great numbers. Aside from the blood pressures the purpose of adding Propranolol was for symptom relief. If you are not feeling any better and it has been awhile trying the two call your Dr. and ask for advice on moving forward.

[~elizabeth~]

I had these effects with the propranolol before weaning off clonidine, that's largely what decided me to try to come off as I feel I might be having a somewhat unusual reaction to it.

It has symptom relief in that somehow it is reducing the postural aspect of my flushing, since starting it I can sit down long enough to watch a film whereas the painful flushing would start after about half an hour after sitting down; that was the case on just clonidine alone, although combining with nortriptyline made it much worse. No one understands why this is happening, this postural flushing problem doesn't seem to have any correlation with BP or pulse rate.

My GP just says 'it's all above my pay grade' when I tell her about these things, and none of the other specialists I've seen say they have the slightest clue about what's going on either, no one has ever seen anything like it before. I feel if we can get to the bottom of why these odd things are happening it might throw some light on things. My current theory is that my alpha 2 receptors are unusually sensitive, so somehow the clonidine is having a greater stimulant effect on peripheral receptors than central ones. Apparently, clonidine can increase the number of peripheral alpha 2 receptors, leading to supersensitivity issues, which is one of the reasons withdrawal effects can be so severe until receptor populations adjust (i'm not sure whether this just applied to alpha receptors on platelets, or blood vessels as well). It also makes them more sensitive to small temperature changes, and I've noticed a significant worsening of these problems last Sept/Oct as temperatures dropped. This is only a theory though, whether I can get anyone to take it seriously I don't know.