Baroreflex Failure/hyperpots - What Is The Difference?

[~elizabeth~]

Given that baroreflex failure and hyperPots share a number of very similar symptoms and diagnostic findings (hypertension, tachycardia, volatility between high/low BP/pulse, high plasma catecholemines, hyperadrenergic symptoms like flushing, sweating, tremor etc), does anyone know what the official differences are between these conditions? I need to know as I want to ensure the correct protocol has been observed during my autonomic testing, as I feel signs of baroreflex failure have been missed.

I think what I have been suffering from is actually a variation of baroreflex failure, albeit milder than the acute kind that causes extreme hypertension. I have POTS and peripheral denervation/blood pooling in my legs, but I feel this has been something of a distraction from the main problem, which is a complete inability of my baroreflex to adjust to supine posture. Although I get tachycardia on standing, it is relatively mild and to be honest isn't bad enough by itself to seek treatment for if it wasn't for the paroxysmal facial flushing/erythromelalgia I get on changing to sitting or supine posture. I don't think it's true hyperPOTS, as I feel better the longer I keep standing, but start shivering/sweating/flushing painfully from the moment I sit down.

Apparently, one highly characteristic feature of baroreflex failure is hypersensitivity to clondine. I was put on this by a dermatologist for flushing 2 years ago, and the drug has caused me nothing but problems, both in terms of severe hypotension/hypoperfusion symptoms and intense rebound flushing/erythromelalgia after only about 4-5 hours (patches are not available in the UK). Combining clonidine with propranolol caused a significant paradoxical rise in BP, and I suffered extreme withdrawal symptoms on trying to come off clonidine. I have felt so much better since coming off it completley, the hypotensive symptoms are gone, personally I prefer to be lucid if slightly 'hyper' than in a permanent stupor on clonidine. Despite taking quite a high dose of propranolol (160 slow release, plus 40mg in advance of sitting/lying down, each time) my BP is still high for me, around 120-140 systolic, although it can drop to 80-90 with low pulse (50s) if I've been supine for a few hours. I have severe 'hyper' reactions to any drugs which affect sympathetic activity (even whilst still on a high dose of clonidine), such as tricyclics, duloxetine, and decongestants such as phenylephrine, which I feel is entirely consistent with being in a hyperadrenergic state.

What I am angry about is that when I had my autonomic tests last year, the hospital did not measure plasma norepinephrine levels, plus I was told there was no need to stop taking stop taking clonidine before the tests. Apparently the results showed a sustained rise of pulse above 120bpm on prolongued standing (i.e. POTS), but no overshoot on the static-handgrip test (which you would expect with baroreflex failure according to my research), presumably because taking 300mcg of clonidine at the time was damping down the sympathetic overactivity. They did not perform a cold-pressor test either, another one that produces a particularly strong result if there is baroreflex failure. I haven't seen a neurologist yet, but my primary concern is that they have missed the salient feature of my problem, namely the lability of BP and intense sympathetic surges on changes of posture. Largely, these are the diametric opposite of POTS in the sense that the worst symptoms are on the adoption of supine posture, not upright.

There seems to be little awareness of hyperadrenergic subsets of autonomic failure in the UK, I'm worried that when I finally do see an autonomic neurologist that they will suggest treating the mild POTS (on an assumption of hypovolemia) with the usual treatments (salt/fludro/midodrine) which will merely make the postural hypertension issues worse. I know other people who have seen the same neurologist who haven't felt their concerns about untypical manifestations of their POTS have been taken on board.

[anna]

"There seems to be little awareness of hyperadrenergic subsets of autonomic failure in the UK,"

I think the Dr.'s in the UK seem to be very one minded as to ANS dysfunction as a whole! which is getting a tad frustrating now. I have no idea what to advice re baroreflex V's Hyper Pots but if you find someone that is willing to think out of the box please let me know!

[Joann]

Elizabeth, I have no answers for you, but am similar to you, in that my heart rate is not really my main concern. Its just the only thing the doctors seem to be interested in looking into. My bp is much more of a concern to me and more debilatating than the heart rate. In fact, when I look back the heart rate was fine at times when the bp was going crazy.

I have often told my family, if I just had high bp like most people. I really wouldn't care as much, those people walk around not even knowing it! I am the opposite I know when my bp is high because I feel awful. Like I am dying! Those symptoms persist even when bp goes down on the meds I am on. They just aren't as bad. I have wondered about baroflex failure, and one doctor a ways back mentioned it but said it would be even more extreme than what is happening, but he did say maybe I was just in the early stages. He had only seen people in the extreme, he was an endocrinologist, who then sent me on to other specialists. My bp changes are with the changes of position. Mostly, when standing up, but sometimes going to sitting or laying from standing. Sometimes it is bad at all times, although usually laying down will bring it down some. They first thought pheo tumor, but now do not think it is.

It has been suggested that I switch to clonodine and I have been reluctant to change, after reading your post I am even more so.

I am going for further testing soon, and actually just posted about medication while testing. The doctor doing the testing said it was ok to stay on them, but your concerns are mine. I wish they would let you stay overnight and come off them with some help.

I hope someone on this site has some insight, although, it sounds as if there just isn't much info available.

[~elizabeth~]

The trouble is that most of the literature on baroreflex failure is where it is acute following injury to the baroreflex nerves, but my hunch is that you can get a more chronic and subtle presentation as part of the autonomic syndrome you get with EDS (in my case) or other conditions that predispose to neuropathy. The fact that it is such a neglected condition, not many references to it even on this forum, means that there is just very little known about it for any specialist to be too categorical about ruling it out.

Remember POTS is 'postural orthostatic tachycardia syndrome' which means the symptoms relate to adopting an upright posture, so increases in sympathetic activity triggered by changes to supine posture must have a different pathology, and I can't think what that could be other than baroreflex.

In one sense, my concerns are slightly academic, I just want to be absolutely sure what is wrong with me before agreeing to any more trial and error with drugs that I strongly suspect will have adverse effects, I'd feel safer if they'd investigate non-adrenergic approaches of lowering BP/cardiac output first.

[bustersacc11]

I have hyperadrenergic dysautonomia per vandy. Vandy dr told me that my clinical picture similar to baroreflex failure but I don't have BF. That was back in 2009. I didn't think of asking them why not. Also, I only had 30 min to ask a million life questions. My next set of autonomic testing coming in may i will be revisiting this issue with them because i feel there is a component of BF to my case. If they say no to BF than I will be asking for an explanation. I get so confused because they all overlap in features and symptoms. I mean there is partial dysautonomia, hyperadrenergic dysautonomia, hyperadrenergic POTS, pseudopheochromocytoma, pheochromocytoma, labile essential hypertension, baroreflex failure, etc. I don't know what is that official characteristic that differentiates the two.

Elizabeth, I have a question. If you can recall the source, where did you find or hear about a characteristic feature of BF is hypersensitivity to clonidine?

Second, I think this topic would be a great Q /A for one of the docs to answer on the next newsletter. How do you get this question to the right person to possibly look at getting it reviewed.

[~elizabeth~]

The patients' maximal systolic blood pressures ranged from 164 to 280 mm Hg, and their minimal systolic pressures ranged from 58 to 96 mm Hg. Plasma norepinephrine and epinephrine concentrations were sometimes many times normal during blood-pressure surges. All the patients had excessive pressor and tachycardic responses to the mental-arithmetic and cold pressor tests and marked hypersensitivity to clonidine. The underlying causes of baroreflex failure included the familial paraganglioma syndrome, neck surgery or radiation therapy for pharyngeal carcinoma, bilateral lesions of the nucleus tractus solitarii, and surgical section of the glossopharyngeal nerves; in two patients the cause was unknown. Therapy with clonidine reduced the frequency of attacks by 81 percent and attenuated the elevated blood pressure and heart rate in the attacks that occurred.

The Diagnosis and Treatment of Baroreflex Failure

Patients with baroreflex failure are often exquisitely sensitive to the effects of alpha 2 agonists to reduce blood pressure

Hypertension and hormone mechanisms ed. Robert M. Carey

[~elizabeth~]

The hypotensive effect of clonidine in the patients was approximately four times that in the normal subjects, but the response to clonidine varied, depending on the initial blood pressure. The clonidine-induced fall in blood pressure was greater during periods of hypertension than during periods of normotension.

The diagnosis and treatment of Baroreflex Failure - Discussion

[~elizabeth~]

That's very interesting BusterSacc. I guess what it all comes down to is how it affects treatment. E.g. if the hyperadrenergic state is secondary to hypovolemia (caused by denervation in the legs) then drugs that simulate or increase norepinephrine will help; if the cause is some sort of baroreflex failure, then it seems to be accepted they will make things worse. That's really what I want to know. My experience is that all sorts of adrenergic agonists or NRIs make things much worse.

Re. differential diagnostics for BF I found this "Disruption of the baroreflex arch is demonstrated by absence of reflex bradycardia and tachycardia in response to intravenous injection of pressor drugs such as phenylephrine and depressor drugs as nitroprusside, respectively. The baroreflex modulation of muscle sympathetic nerve activity can be assessed by microneurography of sympathetic fibres within the peroneal nerve. Additional cardiovascular reflex tests such as Valsalva's manoeuvre, standing up, forced breathing, cold face test, cold pressor test and mental arithmetic can be used to tease out the localisation of the baroreflex lesion."

Baroreflex Failure - a neglected type of secondary hypertension

I have to ay I'm sure if I was injected with either of those, I'd have significant pulse changes ( I nearly passed out when someone gave me metoclopromide intravenously last year, and my pulse shot up horrendously). But then I have peripheral denervation/POTS as well, I can't see why you can't have lesions in both baroreflex nerves within arteries and your leg veins simultaneously.

However, it also says: "Baroreflex failure is essentially different from autonomic neuropathy, which is either primary (pure autonomic failure, multiple system atrophy) or secondary (e.g. diabetes mellitus) In contrast to baroreflex failure which is caused by lesions of the afferent innervation of baroreceptors, autonomic neuropathy is characterised by abnormal efferent innervation to the heart and resistance vessels. The key feature of autonomic neuropathy is (severe) orthostatic hypotension."

[ramakentesh]

Not all pots has a denervation etiology. In some forms of pots there is abnormal baroreflex sensitivity. Mestinon is presumed to work in part at the baroreflex to restrain the over zealous tachycardia and by maintaining parasympathetic input.

in pure baroreflex failure there are profound swings in Bp - 210/100 then supine hypotension. Patients need clonidine or nitro patchs one minute, then are hypotensive the next. I'm not sure tachycardia is prominent but its been a while since I've looked at it so I could be wrong.

[ramakentesh]

Peripheral autonomic neuropathy and baroreflex failure are not normally associated. Hyperadrenergic symptoms in neuropathic pots are thought to relate to denervation super sensitivity, volume status, parasympathetic withdrawal or effects on net.

the innervation of the bar receptors could be compromised although I've not read much on that.

[ramakentesh]

Are you certain your pots has a peripheral neuropathic basis?

[ramakentesh]

Also I responded better to sympathetic medications once my volume status was improved.

[bustersacc11]

One article that you attached and others that I reviewed discuss treating with sympatholytics will reduce serum norepinephrine levels for those dx with BF. So, the violent BP surges and hyperadrenergic symptoms should be suppressed. I get it.

I have been taking Methyldopa for 4 years. While the BP has been controlled and surges decreased the side effects are awful and my quality of life is poor. My catecholamine levels still remain high even with treatment (>600). Recently, I asked my docs about switching to Clonidine and they told me that since Methyldopa and clonidine are in the same class of drugs and both have similar effects of reducing sympathetic tone and would have similar side effects they prefer that I stay on Methyldopa and have found methyldopa to provide more steady effects and that the advantage of methyldopa is that it reduces activation of both alpha and beta receptors.

Last month, after 4 years I asked about switching BP med to Cozaar. Autonomic Dr was not opposed to me trying Cozaar. Not sure it will help but told me to try it and if feels like it is working to taper off Methyldopa. Cozaar is a angiotensin II blocker. Angiotensin II stimulates the release of both norepinephrine and epinephrine into the blood stream. By taking a angiotensin II blocker findings have suggested, specifically cozaar, has been helpful with the prevention of chronic or intermittent sympathetic hyperactivity. Further, cozaar has shown to decrease plasma levels of norepi. When I weened off Methyldopa and was only on Cozaar I felt horrible. While my blood pressures were controlled and no surges, I felt full of adrenaline.

I abandoned my experiment but am taking both Methyldopa and Cozaar right now. It is a effort to achieve some sort of balance with improving my symptoms and BP with minimal side effects. Last week, I had my catecholamines checked per my request and my standing norepi still high. Came back above 700.

I am so lost. Really, I have no other ideas left when it comes to experimenting with treatments to get symptoms relief .

[kitt]

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[ramakentesh]

Methyldopa and have found methyldopa to provide more steady effects and that the advantage of methyldopa is that it reduces activation of both alpha and beta receptors.

Last month, after 4 years I asked about switching BP med to Cozaar. Autonomic Dr was not opposed to me trying Cozaar. Not sure it will help but told me to try it and if feels like it is working to taper off Methyldopa. Cozaar is a angiotensin II blocker. Angiotensin II stimulates the release of both norepinephrine and epinephrine into the blood stream. By taking a angiotensin II blocker findings have suggested, specifically cozaar, has been helpful with the prevention of chronic or intermittent sympathetic hyperactivity. Further, cozaar has shown to decrease plasma levels of norepi. When I weened off Methyldopa and was only on Cozaar I felt horrible. While my blood pressures were controlled and no surges, I felt full of adrenaline.

Interesting.

Clonidine acts by decreasing overall sympathetic outflow centrally, so it to would also reduce activation of alpha and beta receptors.

Angiotensin II does indeed have potent central effects with stimulate sympathetic activity. In the Low Flow POTS sympathetic excess is a prominent feature and may relate to local and also central effects of angiotensin II according to some research.

True 'florid' Hyper POTS is by far the hardest to treat because you have such intense elevations in sympathetic activity but in some still impaired cerebral autoregulatuion.

[bustersacc11]

Hey Kitt!

You are correct the half-life of Methyldopa is 1.7hrs. Also, which is important to consider is the time action/profile (antihypertensive effect) of the medication. For example, Methyldopa onset 12-24h, peak 4-6h, and duration 24-48h. Versus Clonidine’s half-life is 12-20hrs. The action/profile shows onset 30-60min, peak 2-4h, and duration 8h. Notice that the drug’s effect and its blood concentrations (half-life) are not always perfectly correlated. It takes somewhere between 5 and 6 half-lives for a medication to reach steady state. Medications with short half-lives (like Methyldopa) reach steady state relatively quickly, but takes a little bit for the ant-HTN effect to peak, while those with long half-lives (like Clonidine) take a long time to reach steady state but its effect is pretty quick. Bit of a difference.

Just making you aware as a forum friend when you take Methyldopa. I understand it works for you and I am glad you are getting rest. Just be careful stacking those doses close together.

I am just running scared. Could I go back to Vandy? Yes. I am in communication with them about my case quite often. They are awesome. Sometimes you need another set of eyes on your case from time to time. I have learned over the years each facility does things a little different. This year I have decided to go back to Mayo. In fact, my Vandy Dr. was not opposed to it and said he never discourages other’s opinion. It was said with professionalism and class. No egos hurt. Without hestitation Dr. Feeley agreed to see me again and recommended that I come off everything beforehand. UH!!

[bustersacc11]

Ramakentesh:

What my brain was telling me to type doesn’t always come out as planned. Clarify my sentence. Yes, that is correct about Clonidine. Vandy doc’s point with my case, while the two drugs reduce activation of alpha and beta receptors Methyldopa provides steadier effects and less side effects versus Clonidine from their experiences.

Absolutely correct about Ang.II. The RAS moderates sympathetic tone not only by acting on the CNS, or by increasing the release of catecholamines from the adrenal medulla, but also by a local effect on sympathetic nerve endings in the tissue. You can understand why I was very excited about taking Cozaar. I really thought this will work. Control BP, suppress BP spikes, and reduce plasma norepi levels so I won’t have that feeling of adrenaline overload with minimal side effects. Didn’t work. STINKS!

I do not have POTS. Never have. Slow HR with PM. I guess while central hyperadrenergic POTS is less common and more complicated my case is probably even less common and equally complex. I fall into the hyperadrenergic subgroup partly based on my catecholamine levels. That’s why I appreciated Elizabeth’s topic. Since I don’t have central hyperadrenergic POTS (even though it appears they have some BF impairment) I was back speculating if I have baroreflex failure. Nevertheless, I thought I should have seen better results with my catecholamine blood levels taking Methyldopa and Cozaar. I changed my focus while taking Methyldopa and Cozaar and told myself catecholamine levels are not predictors of how well treatment is going; rather, how do I feel. Well, catecholamine levels are still high and I feel like crap.

[bustersacc11]

Elizabeth:

Thanks for the articles. There is something to be said for the drugs that we experiment with and the path it takes us down. Years ago I had the radionuclide study done at CC. Results were normal blood volume but marked venous pooling was noted. I tried TED hose, abd binder, etc. Nothing worked. Specifically, when I tried licking the stick with Midodrine I had very high blood pressure spikes and the adrenaline flood gates were opened. I had to quickly abandon that option. Anything that triggers or mimics adrenaline sends me into a tail-spin. Is the excess norepi in my blood stream disrupting communications and causing my symptoms a partial dysautonomia, BF, or something else. I have never been able to pin them down to give me a conclusive dx. This has been going on for 5 years.

Your point about differential diagnostics sounds like a chronotropic incompetence effect. I doesn’t sound like it applies to me either.

[ramakentesh]

Yeah it ***** that cozaar didn't help. Phentobarbitol??

[kitt]

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[bustersacc11]

Half-life is the chemical breakdown of a drug. How it is metabolized and eliminated. Methyldopa’s half-life is 2 hours. For example, you take 250mg of Methyldopa at 9pm. By 11pm half of the drug is metabolized to 125mg. By 1am 62.5mg. 3am 31.25mg and so on until it is eliminated from your body. Kitt what is important that while we keep taking Methyldopa, and it is being metabolized and excreted the BP effects of the drug are still working. We are trying to achieve a steady effect and normalize our blood pressures. Please, keep in mind that I am sharing with you a very small snap shot of pharmalogy. There is a lot more to this. I am far from an expert.

The peak level is the highest concentration of the drug in the blood. Meaning, with Methyldopa the maximum decrease in blood pressure occurs four to six hours after you take it. Which for you based on your times appears to be around 3 to 4am.

Then, onset of action is the time required after taking the drug for a response to be observed. What this means is once an effective dosage level is attained, a smooth blood pressure response will occur in about 12 to 24 hours. For me, one pill a day doesn’t work. An effective response doesn’t last 24 hours for me but usually a part of the day so that’s why I take it twice a day. To get that 24 hour response. Further, it may explain why you feel revved up during the day and full of adrenaline. You may have not achieved that effective dosage level to have a smooth BP response. I don’t know if I would take both Methyldopa and Clonidine. They are the same drugs. If you tolerate Methyldopa, maybe talk to your Dr about adding another dose during the day. It is not uncommon for some people to take it three times a day.

Lastly, duration of action is the amount of time that a measurable drug effect persists. Meaning, if you stopped taking Methyldopa after an effective dosage level was attained, a withdrawal will occur, and it takes about 24 to 48 hours to return to our crappy selves.

Yes, it does add to my fatigue and lightheadedness. Some days are worse than others. That has been the trade off the past four years. Stopped the surges but hasn’t helped my other symptoms, worsen some, or improved the quality of my life. That’s why I was hoping Cozaar would have worked.

For normal people out there with HTN, there is a reason why millions of people take drugs like Cozaar to treat high blood pressure and no longer take Methyldopa. Yes, they have found different ways to address and tackle high blood pressure BUT it has way less side effects.

If this didn't help clarify things, let me know via PM.

[kitt]

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[issie]

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[ramakentesh]

Do the effects of glutamate or gaba effect central autonomic control in the per ventricular or brain stem regions? I think se plays a role.

[issie]

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