Clonidine Increases Blood Volume?

[Anoj]

I found that info listed here:

http://en.wikipedia....tic_intolerance

Medications that increase blood volume:

• Fludrocortisone (Florinef)
  
• Erythropoietin
  
• Hormonal contraception
  
• Clonidine
  

Did not know that - don't know if it's true. Does anyone know?

I find it interesting, especially since a lot of hyper POTS patients report better results with clonidine vs. a beta blocker. I have been thinking about switching from a beta to clonidine but have been putting it off. I wonder if this is the push I need.

[McBlonde]

I didn't know that either! Clonidine is what my doctor just prescribed for me. Thanks for posting!

[flyingsquirrel]

This is not really accurate. Clonidine is an centrally acting alpha-2 agonist which means that it decreases the amount of circulating norepinephrine, thereby reducing blood pressure and, to a lesser degree, heart rate.

Without going into the intricacies of renal physiology, clonidine, at normal dosages should not have any significant effect on kidney function. There will be a SLIGHT reduction of blood pressure within the kidneys due to the decreased levels of norepinephrine, however the kidneys have much more sophisticated ways of regulating renal blood flow and these systems are not affected by clonidine.

Clonidine also inhibits renin secretion. This has two important consequences. The first is that a lack of renin inhibits the conversion of angiotensinogen to angiotensin, thereby (further) decreasing blood pressure. The second is that without angiotensin, aldosterone is not secreted (remember florinef=aldosterone) and sodium and water are lost, thereby DECREASING blood volume.

Now, when used for extended periods of time, people who had problems with sodium (and water) retention can develop a "tolerance" to clonidine and (re)develop symptoms of sodium and water retention. There is nothing in the primary literature to suggest that this is an effect of the drug itself.

[Anoj]

I am going to have to re-read what you wrote. Thank you for the insight! I had a feeling it might not be true. Wiki isn't the best source.

[flyingsquirrel]

True, but it isn't all wikipedia's fault. When new drugs are studied for use in humans they go through a specific series of clinical trials. Part of these clinical trials is recording the "adverse effects" or side effects of the drugs. However it is nearly impossible to parse out what symptoms are caused by the drug, what symptoms would have happened anyway (even in placebo controled trials), and what symptoms are due to underlying medical conditions. Parts of the transparency regulations stipulate that EVERY adverse effect experienced during a clinical trial must be recorded and must be atributed to the drug being tested unless it can be definitively proven otherwise (something that is rarely attempted and almost never successful). This is why, if you read the package insert, pretty much every drug has "headache" and "nausea" and "sinusitis" listed as side effects. It's not that the drug caused headaches, nausea, and sinusitis, it's just that over the course of a multi-month clinical trial several people were bound to get headaches, feel nauseated, and get sinus infections...and the FDA mandates that these be reported as "adverse events." The validity of this method can be argued in another forum. I have my issues with the FDA, but this is not one of them...my problem is how this information gets misinterpreted and mis-applied.

Sometimes drugs, especially ones that are prescribed "off label" are given not for their primary effect, but for a specific side effect.

Take pyridostigmine (mestinon) for example. The primary effect of pyridostigmine is decreased muscle weakness (primarily prescribed to people with myasthenia gravis), however a significant side effect is bradycardia. I don't have any problems with muscle weakness. I do however have a big problem with tachycardia. I was prescribed pyridostigmine to try to bring my heart rate down, therefore I take this drug for the side effect.

I think (and I have no evidence of this) that this was the thought process of whomever listed clonidine as a volume expander: They might have seen "sodium and water retention" listed as a side effect (see above as to how it got listed as a side effect) and without thinking about the mechanism of action of the drug, misinterpreted this data, decided that this must be a common side effect and therefore clonidine could be given for the purposes of eliciting that side effect.

[issie]

Interesting description of why clonidine increases volume - because of a tolerance to the drug and therefore breakthrough. I took clonidine for a few months. At first I found it very helpful, it definitely gave me more of a leveling effect of the drastic bp swings and therefore a more leveling effect of the swings in heart rate. But, towards the end (when I decided to go off it) it was causing more edema and fluid retention. One thing that was pretty consistant with it - was fatigue. It really made me feel tired and that never got better. It makes sense that if you slow the sympatehtic system down - it is going to cause more fatigue. (Most peope I've talked with seem to find this to be true with Beta's too.)

Interesting the connections with aldosterone and renin. Since I have low levels of both of these - it was compounding my issues with my kidneys in the long run. I definitely attribute "some" of my edema to this drug. But, not all of it. I will, however, keep this drug as a reserve drug and will go back on it - if my bp and hr get back to that drastic, unpredictable swinging. It did level that out and it was wonderful to have a break from it for a few months. But, it wasn't something I could stay on indefinitely.

Flyingsquirrel, may I ask what your background is - that you know so much about this?

Issie

[McBlonde]

Now I am so confused on why Dr. Grubb ordered Clonidine for hyperadrenergic pots if it shuts down your own renin?

[brethor9]

yeah I never understood that concept either? I mean I believe beta blockers do the same? so we take florinef to build those levels up but the beta blockers and clonidine cancel those effects....so whats the point? what am I missing?

Bren

[flyingsquirrel]

issie... You bring up an interesting point with clonidine and fatigue. In addition to all the reasons you mentioned, alpha-2 receptors are involved in consciousness. As a centrally acting alpha-2 agonist, it makes sense that you would feel some of these effects. In fact, there is a 'hot new' ICU sedation drug (dexmedetomidine) that is also an alpha-2 agonist.

As for your question, you might say that I have a "bit" of medical training. I would be happy to answer in more detail if you want to PM me.

McBlonde... I won't dare to challenge the great Dr. Grubb, (and correct me if I'm wrong) but isn't the problem with hyperadrenergic POTS too much norepinephrine? Clonidine increases alpha-2 activity which helps bring down levels of norepinephrine.

[McBlonde]

I don't know.... Dr. Grubb doesn't recommend Florinef for his hyperadrenergic pots patients on that treatment plan that was posted which I am now trying to find where I filed!!

[brethor9]

thats weird Mcblonde!..... I have major high catecholamines and yet my specialist put me on florinef and beta but did not like the idea of Clonidine....he suspects my nerves are effecting the constriction/dilation issues and somehow Clonidine adds to that....I forget the whole explanation ......goes to show how treatment can vary so much

Bren

[McBlonde]

yes, he does.. but now after readying what you posted.... I'm sorta freaked out. Mine renin levels were low to start with and so Clonidine would make my renin even lower?

[McBlonde]

thats weird Mcblonde!..... I have major high catecholamines and yet my specialist put me on florinef and beta but did not like the idea of Clonidine....he suspects my nerves are effecting the constriction/dilation issues and somehow Clonidine adds to that....I forget the whole explanation ......goes to show how treatment can vary so much

Bren

I know! Here's the link to the treatment plan: http://circ.ahajournals.org/content/117/21/2814/T2.expansion.html

[flyingsquirrel]

The effect of clonidine on renin (and therefore on aldosterone) is MINOR compared to its effects on alpha-2 receptors.

Also, keep in mind I'm explaining how it works in non-POTS physiology...things could be different for you.

[brethor9]

well I know I had to stop the beta blockers because they were making things much worse pooling wise and irritating the mast cells.....but if you research beta blockers and then florinef and the mechanism....they seem to cancel each other out....off topic but I also read an article today on florinef that basically said it is one component different from cortisol? that perked me up a bit....I wonder how many of us have cortisol issues which lead to adrenal issues? Could be why florinef is really hard for some patients to get off of? I really sometimes wonder if this illness isn't based in endocrinology somehow??

[McBlonde]

Thank you! I'm sitting here with a prescription for Clonidine and one for Wellbutrin. I have hyperadrenergic pots. Saw my primary care doc Tues. and he freaked out over Clonidine and Wellbutrin, lol... So, I'm still sitting here debating with myself on which one to try first. There is all very hard when you've had bad experiences with meds to start with. Any thoughts on which one you would take first?

[flyingsquirrel]

I can't give you any advice on that one...only sympathy with the bad med experiences. I just got put back on the same drug that sent me to the ED in respiratory failure multiple times because it is the ONLY thing that is FDA approved that can keep my heart rate down.

[brethor9]

personally I would try the clonidine first at a very, very low dose......I have just started my autistic son on it and so far no issues.....but it really has to be your choice I wish you the best with whichever one you try and crossing my fingers you have no really yucky side effects..... keep us posted

Bren

[flyingsquirrel]

brethor... what do you mean beta blockers and florinef cancel each other out?

Florinef aproximates the function of aldosterone and causes the retention of sodium and therefore water. This increases (or prevents the loss of) blood plasma volume.

Beta blockers prevent the activation of beta receptors by epinephrine (and to a lesser extent norepinephrine) which leads to a decrease in heart rate and blood pressure.

[brethor9]

I was thinking more along the lines of renin production.....doesn't one drug (florinef) increase the level and the other ( beta blockers more than alpha) decrease it which affects the alderstone production? also one drug raises BP and the other lowers it...beta's made my blood pooling way worse too... for me personally it was like they cancelled each other's good effects out....just not a good combo for me....but again everyone's system is different

[flyingsquirrel]

You're right about beta blockers decreasing renin secretion (I had completley forgotten about that). However I've never heard of florinef increasing renin levels, nor has a quick check of my favorite references yielded anything to that effect. Do you have any resouces that support this?

[issie]

Florinef basically is a synthetic form of aldosterone. Aldosterone helps you to retain salt in the kidneys and therefore in the body. The idea is if you retain more salt in your body, maybe you will retain more fluid. The florinef will lower the bodies own production of aldosterone. (Because you are supplying it to the body and your body just doesn't need to make more on it's own.) That's probably why people have a hard time coming off - because sometimes maybe the body doesn't go back to making it on it's own.

Betas and clonidine - work on a different thing - has to do with the sympathetic and parasympathetic functions - more on the nervous system function. Also, plays a big part in the heart and circulatory function because of blocking of certain catecholamines.

Okay Bren, for us with MCAS - we can't use beta blockers it will cause a degranulation of the mast cells and makes us a whole lot worse. Clonidine is one that is considered okay for us with mast cell issues. However, I did find that clonidine made my edema issues worse - over time. But, one of the newest things I've learned in regard to edema is when we have a mast cell release - there can be an issue with leaking of our veins into tissue - that in turn causes us to be hypovolumic (low blood volume - because of the loss of fluid) but, have edema at the same time - because it doesn't stay in our veins like it's supposed to. Then if there are EDS veins on top of that - then you've got compounded problems. I've found that I can't take a vasoconstricting drug - it makes me much worse. But, vasodilating is better - but, have to be careful to not take too much or there is the pooling problem.

With POTS it's very common for them to give you one medicine and then give you another one to counter-act some of the side effects of the first one. It's a fine balancing act of opposites. They do this for many types of problems. No wonder older people are on so many meds. Like for example === high blood pressure - they give you one medicine and if that doesn't work well enough - add another one - if it causes edema they add a diuretic etc. It keeps going on and on and on. Some things are sucessful - others not so good.

Issie

[brethor9]

Thanks Issie I knew you would come along and straighten me out lol......its the MCAS that is the wild card....because of that meds just don't work the way they should never mind the dysautonomia on top of everything. I asked my specialist to try me on clonidine but he didnt think it was a good idea? he said it was something to do with my possible underlying peripheral neuropathy? if I understand correctly it can affect how the nerves signal to the blood vessels? and that is where my body may be having a problem.....if that makes any sense...... what am I saying? NONE of this makes any sense

Bren

[brethor9]

Issie....also the point you make about MCAS and edema makes so much sense.....it may explain why I am constantly low in blood volume yet retaining fluids in all the wrong places.... I am the same way I can't constrict too much or dilate too much or I get sick.

[McBlonde]

and just to add to the confused way our bodies work.... after I started having hypertensive episodes I stopped taking the Florinef that I've been on for years. I can't tell the slightest bit of difference (except I'm not peeing all the time)