Propantheline Bromide

OK; so we all know that this is the illustrious ***********'s personal pet project, but despite the fact that he has obviously got peoples' backs up here on this forum for other reasons, isn't the option of trying to reduce STRONGLY-VAGALLY-mediated LAF episodes with PB not worthy of more detailed discussion here on this forum?? My own AF episodes are DEFINITELY vagal and, as such, I am obviously personally very interested in JB's PB approach to limiting/eradicating AF episodes.

I've personally corresponded with JB about PB and have found his information both well and fairly presented and very interesting.

I'm thinking that GeorgeN would in particular have a lot of views and opinions on the PB-based approach. I'm also sure that PC would have a LOT to contribute too as I remember he used to put forward the anticholinergic properties of disopyramide as one of the reasons it used to work so well for him as a vagal LAFr.

So, George, Hans, Erling and all; what do you think to trying PB for vagally mediated AF??

Mike

It's a shame that ******* has caused so much turmoil on this site. I wish he could be a bit less abrasive, but I guess we cant all be diplomats.

I too would like to see more discussion on this topic. I find it very interesting, as all other approaches have failed me.

My main concern is that, if I understand it correctly, PB lengthens your QT interval. I'm not sure I like the sound of that. Perhaps its harmless, I dont know. I do know we had one poster tell his story of how a lenghtened QT killed him, several times. He was lucky to be back here telling his story.

I wish our resident experts would reply before this thread is deleted.

****** may be a *****, but this topic deserves discussion.

Mike,

The whole concept of vagolytic meds seems to be an underexplored area. PC used disopyramide, however it has the same risk as some other anti-arrhythmic drugs (AAD)- namely torsades de pointes.

I posted about Propantheline Bromide to Jill here:
<[www.afibbers.org];

and in the same thread here:
<[www.afibbers.org];

In my post to Jill, I reference the AERP relationship. We are obviously trying to lengthen it with our electrolyte supplement intake. This does work for some (like me, thankfully), but not all vagal afibbers. Obviously in the 12 step plan [www.afibbers.org], you'd like to see if steps 1-9 worked first. If they did not, then I think a reasonable approach would be to try a vagolytic med before trying an AAD, like flecainide.

Additionally, I looked up Urecholine [www.medicinenet.com], one of the other meds mentioned by Dr. Reiffel. One of the uses is: "This drug may also be used to treat heartburn. It works by helping the stomach muscles move food down out of the stomach faster and by increasing the strength of the muscle between the esophagus and stomach (lower esophageal sphincter). This helps prevent food/acid in the stomach from rising back into the esophagus." I found this interesting since many here have stomach & GERD issues.

Tincture of belladonna [www.botanical.com] is also mentioned by Dr. R.
====================================================
In the link it mentions: "--Medicinal Action and Uses---Narcotic, diuretic, sedative, antispasmodic, mydriatic. Belladonna is a most valuable plant in the treatment of eye diseases, Atropine, obtained during extraction, being its most important constituent on account of its power of dilating the pupil. Atropine will have this effect in whatever way used, whether internally, or injected under the skin, but when dropped into the eye, a much smaller quantity suffices, the tiny discs oculists using for this purpose, before testing their patient's sight for glasses, being made of gelatine with 1/50000 grain of Atropine in each, the entire disk only weighing 1/50 grain. Scarcely any operation on the eye can safely be performed without the aid of this valuable drug. It is a strong poison, the amount given internally being very minute, 1/200 to 1/100 grain. As an antidote to Opium, Atropine may be injected subcutaneously, and it has also been used in poisoning by Calabar bean and in Chloroform poisoning. It has no action on the voluntary muscles, but the nerve endings in involuntary muscles are paralysed by large doses, the paralysis finally affecting the central nervous system, causing excitement and delirium.

The various preparations of Belladonna have many uses. Locally applied, it lessens irritability and pain, and is used as a lotion, plaster or liniment in cases of neuralgia, gout, rheumatism and sciatica. As a drug, it specially affects the brain and the bladder. It is used to check excessive secretions and to allay inflammation and to check the sweating of phthisis and other exhausting diseases.

Small doses allay cardiac palpitation , and the plaster is applied to the cardiac region for the same purpose, removing pain and distress.

It is a powerful antispasmodic in intestinal colic and spasmodic asthma. Occasionally the leaves are employed as an ingredient of cigarettes for relieving the latter. It is well borne by children, and is given in large doses in whooping cough and false croup.

For its action on the circulation, it is given in the collapse of pneumonia, typhoid fever and other acute diseases. It increases the rate of the heart by some 20 to 40 beats per minute, without diminishing its force.

It is of value in acute sore throat, and relieves local inflammation and congestion.

Hahnemann proved that tincture of Belladonna given in very small doses will protect from the infection of scarlet fever, and at one time Belladonnna leaves were held to be curative of cancer, when applied externally as a poultice, either fresh or dried and powdered.

Belladonna plasters are often applied, after a fall, to the injured or sprained part. A mixture of Belladonna plaster, Salicylic acid and Lead plaster is recommended as an application for corns and bunions. "
====================================================

Belladonna looks a bit riskier to me. I'd like Dr. R's input on how he used it before going any further with it.

As I mentioned in my post to Jill, I would like to explore vagolytic meds further, but have not had the time to do much proper research. Jill has corresponded with me. She had her ND review the materials. The ND encouraged her to go to the next step, so she will approach her GP about a prescription for Propantheline Bromide (P. I don't know if she was able to get this script. If she uses it, I asked her to report back here, so we have more data.

Additionally, the author of your referenced single case study corresponded with me regarding PB and sleep apnoea. He suffers from apnoea and used an appliance while sleeping to keep his airway open. Subsequent to use of PB, he no longer needs the appliance. I queried whether, absent afib, he would take PB just for keeping the apnoea away. He replied that he would take a low dose.

Cheers,

George

Hi George and others interested in PB,
I have been researching the use of this drug for my afib. I have exhausted most other means to control my episodes and did ask my GP for a prescription. Although very sympathetic, he would not prescribe it for me. I can respect that, as I am asking for it for an off-label use. That will be a problem for anyone attempting to use PB. He took the literature I gave him, intending to read it and would like me to try again with an EP he recommended. That's where I stand as of now and will report back when or if I can get the prescription. Jill

Mike,

I have no comments or further references regarding propantheline bromide.

Hans

Thanks for all the responses.

Hans, whilst I certainly respect and admire you for providing this excellent forum, it does seem a bit of a shame that my posted link to **** *****'* website was removed since whatever else the man is or isn't the information there is for VMAFrs like me provocative and well-presented. It seems a shame that the man's abrasive nature has effectively killed off what seems to me would be some valuable discussion/debate on this aspect of the ANS and AF. But I guess that I can appreciate that for one reason or another you don't want to encourage **** ******'* further participation here on this forum.

George, good info and I obviously agree that vagolytic meds are in need of further examination and discussion for VMAFrs.

Jill, my own doc here in the UK will give me a prescription for PB, but then again he is also a friend and knows and respects my own abilities and caution as a able researcher and cautious individual respectively. I'm seriously thinking of giving PB a go, but not until my present daily Flec regimen of 50mg am and 75mg pm starts to significantly lose its efficacy.

Curt; ditto to your comments!

Kind regards to ALL!

Mike

mike--

I am also interested in learning about Propantheline Bromide, but am satisfied to research it on my own. I definitely do not care to read the sarcastic, belittling, abrasive posts of **** on this BB. It caused me a great deal of stress to see his postings, and am very relieved that Hans has used his judgement to remove xxxxx from the Forum. At times his posts left me feeling on the verge of Afib.....really!

Louise

Mike - these links may help you with your research... be sure to read completely. Jackie

[dailymed.nlm.nih.gov]

[www.ncbi.nlm.nih.gov]

[medical-dictionary.thefreedictionary.com]

[www.rxmed.com]

Mike,

My thought is to develop a fully referenced paper on vagolytic meds generally. Such a paper could be used by people like Jill to educate their physicians who are reluctant to prescribe vagolytic meds. Perhaps Dr. Reiffel would communicate with us or review the paper for accuracy. Unfortunately I have little time to devote to this task at present. So any collaborators would be welcome. Doing it alone, I will accomplish it eventually, but it will be prioritized as a community service project on my plate of activities.

George

Yes, it's too bad personality got in the way of possibly good info. I am glad to see this subject brought up again in a much more rational way.

Kudos to all the rational minds.

Lisa

It's not You v. Me, it's US v. IT.

Mike,

I talked my GP into writing a prescription and tried Prop Bro for 30 days.

I had no afib during this 30 day period. I am a mostly vagal affibber, one year post ablation. Prior to my Prop Bro "trial" I was experiencing episodes roughly twice a month.

After taking Prop Bro for 30 days I experienced severe blurred vision (both near and far vision). I stopped the drug and my vision improved within a week (although my near vision is still somewhat different).

I had an afib episode 3 days after stopping the drug and another episode 8 days later.

So based on my unscientific trial, I believe that Prop Bro helped my afib. I also believe that the impact it has on my vision is an unacceptable side effect. I would be very interested in trying another anticholinergic drug (without the vision side effect of course).

EB

EB- What was the dose of Propantheline you were taking? I read about the potential vision side effects and am curious . And how were you able to talk your GP into it?

EB - were you taking the PB multiple times a day? As I understand it, you would not need to take PB in the morning if you only had nighttime episodes.

Obviously, it would make sense to take the lowest dose that was still effective.

George

George,

I wonder if a transdermal scopolamine patch might work as well as the propantheline bromide?

[en.wikipedia.org]

It may be easier to get a prescription for that???

Hans

I am blessed with a GP who actually listens to the patient and I brought in material from this forum on PB. My GP was quite familiar with the drug; he said it was commonly prescribed for GERD back in the days before Nexium and Zantac were available. Since I have a GERD history, he prescribed the PB for GERD.

My initial dosage was 7.5mg twice a day; after about a week I noticed my vision changing and after about 10 days I reduced the dose to 7.5mg at bedtime (75% of my afib episodes are noctural).

Even with the reduced dosage my eyesight continued to be affected.

A couple of weeks after discontinuing the drug, I tried a quarter dose- 3.75mg at bedtime. My vision changed almost immediately.

Obviously I am very sensitive to the vision side effect but I am convinced that it was doing the ****on my afib.

EB

George,

Further to my message about scopolamine I was wondering if Gravol (dimenhydrinate) might work for vagal afibbers. It has anticholinergic effects and, of course is also an antihistamine which may be OK for vagal afibbers. You can read about it here:

[www.hamiltonhealthsciences.ca]

Hans

Hans,

That looks interesting. For EB, it may have some of the same issues as PB, since blurry vision is a potential effect.

As to the other meds mentioned by Dr. Reiffel, urecholine looks like it might act somewhat differently.

As to tincture of belladonna, Donnatal is prescribed and comes from belladonna. The prescribing warnings look a lot like PB. There is not a lot of normal prescribing info, that I can find, on tincture of belladonna.

EB might want to explore urecholine. Someone like Jill, whose having a hard time getting a prescription may see if they have success with dimenhydrinate.

EB's case is instructive. I think it makes sense to start with a very low dose and titrate up to what is needed to stave off afib without side effects.

Thanks!

George

Long, long, long ago, I was prescribed Donnatal for GI issues. I only took it briefly, as it caused my vision to become blurry. Sorry I can't remember the dose.

Louise

I am sure that I have read that antihistamines, antiparkinson drugs, tricyclic antidepressants all have anticholinergic effects - I wonder if it is worth looking at these as part of this discussion too?

Mike

George,

Here is a discussion of antihistamines in relation to their toxicity as related to their anticholinergic effects:

[emedicine.medscape.com]

Please let me know your conclusions as to whether AHs are worth a look for VMAFrs!

Regards,

Mike

Mike,

One of my concerns in venturing too far from Dr. Reiffel's suggestions is the issue of anticholinergics and cognitive impairment.

"Anticholinergic drugs block a nervous system neurotransmitter called acetylcholine. Those suffering from Alzheimer's disease typically have a marked shortage of acetylcholine."

From: [articles.mercola.com]

When I queried about this issue with respect to PB, the response I got was, "Propantheline bromide is one of the few anticholinergics that do not cross the blood/brain barrier, so cognitive impairment might not be a concern."

A little research indicates the list of drugs with anticholinergic properties is quite extensive.

"Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study" [www.ncbi.nlm.nih.gov]

A Google search on anticholinergics risk cognitive impairment
[www.google.com]

These meds clearly have some potentially serious issues. If they are to be used successfully, finding the lowest possible effective dose, without side effects would be an imperative. I'd like to have Dr. Reiffel's input on what he's seen from long-term usage.

Regards,

George

For this post, this definition will be useful:
[en.wikipedia.org]
Muscarinic acetylcholine receptor

Muscarinic receptors, or mAChRs, are G protein-coupled acetylcholine receptors found in the plasma membranes of certain neurons[1] and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system.

I posed the question of dosage and mechanism of PB to a patient who has used it. Here is the response.

================================================
PB is an unusual drug in that it is patient specific. The therapeutic range is huge; it can range from 7.5mg per day to 75mg per day to get the same effect in different patients. Side effects mean a patient is taking too much PB. Dr. Reiffel recommends lowering the dose until all side effects are gone and that is the correct dose for that patient. In any case, the same daily dose of PB will give a different outcome each day depending on what food is in the stomach etc. Antacids especially should not be used an hour before or after PB administration as they ruin the effect. PB is especially sensitive to what is in the stomach when it is taken. Most of the PB dose is NOT absorbed by the body anyway.

After a month or two the body manufactures more muscarinic receptors (MRs) which soak up the PB and reduce side effects. But it does not keep producing increased MRs exponentially. After a while it settles down to a stable number and you can adjust the dose of PB to an optimum level for years to come. But side effects are not optimal. It should be possible to control the afib below the side effects threshold. Dr. Reiffel says that with PB patients should NOT put up with side effects. Keep reducing the dose until they cease. However, vagal afib will still be under control.

With an antiarrhythmic drug you often have to endure the side effects in order to receive the therapeutic dose to control afib. PB is different. It is not an antiarrhythmic and it does not work like one. PB is an acetylcholine blocking mechanism. It does not affect the electrical conductivity of heart tissue. It's effect varies on each patient depending on how many muscarinic receptors they have. The correct dose to control afib is just below the side effects threshold. Do not treat it like an antiarrhythmic drug.

Antiarrhythmics like flecainide etc eventually cease working because they become overwhelmed by the harm being done to the atrial substrate by things like excess acetylcholine. So they "wear off" and the patient needs an ablation to end his suffering. PB does not wear off once the plateau of equilibrium has been reached - approximately two to three months after the initiation of the drug. The excess acetylcholine is controlled and the heart tissue repairs. At the same time the PB will allow damaged tissue in the stomach and gut to repair because that same excess acetylcholine was damaging the digestive system as well as the heart atria because it overstimulated gastric acid and digestive juice production. The PB will also improve the sex life as it reduces premature ejaculation problems caused by excess acetylcholine. PB also seems to help sleep problems by controlling acetylcholine during the night. It reduces a certain type of nocturnal anxiety caused by acetylcholine and also helps with the sleep apnoea problem.

When first using PB, blurred vision, light sensitivity, nausea, very dry mouth, urinary hesitation, even tachycardia can occur. Reducing the dose along with time allowed the problems to fade while afib was controlled.
================================================

I think these are key issue to understand better:

"Those suffering from Alzheimer's disease typically have a marked shortage of acetylcholine..."

"Propantheline bromide is one of the few anticholinergics that do not cross
the blood/brain barrier"

and

"PB is an acetylcholine blocking mechanism"

I think it will take some study on my part to get up to speed on the biochemistry here.

I'd love other comments.

George

George,

At first glance, it sounds like it may be very beneficial to vagal AFers (me, me, me). I do have one question right away: if I understand correctly, it is an antihistamine, and thus would be contraindicated for those with HBP. Do I have that right, or am I way off base?

I am certainly no chemist or have any sort of science background beyond what it takes for an art degree, so I appreciate those who can help us understand it in English.

Lisa

Lisa,

I would say that many antihistimines have anticholinergic properties, but not all anticholinergics are antihistimines.

I do not believe that Propantheline Bromide is an antihistimine. I'm not sure of how it would interact with blood pressure.

As I research this further, I would not wish to stray too far from what Dr. R. has used - Propantheline Bromide, Urecholine & Tincture of belladonna. I would be careful with any of it. Used improperly, these are not benign agents.

If I were to start a routine with one of these meds, I'd start low and see how little I could take and prevent my afib and hopefully avoid side-effects, rather than starting high and working down. I'm not a big fan of side-effects.

These meds look good in a relative sense - in comparison to many of our anti arrhythmic meds that can have such side effects like Torsades de pointes (a form of ventricular tachycardia).

If you or others want to talk to your physician about this protocol, I can email you PDF's of Dr. R's papers for them to review.

George

So the idea occurred to me, "What is the least toxic, effective, vagolytic agent?

Some searches I've pursued on this path are below. No great answers yet - just rabbit trails to follow.

[www.google.com]

[www.google.com]

[www.google.com]

[scholar.google.com]

George,

Not sure I'm ready to take the plunge, yet! I have an appointment later this month with my cardio, so I would appreciate the papers, so that he can take a look at them and give me his thoughts.

Thanks so much for setting me straight and translating into the only language I can read :-) I'll be looking for the email.

Regards,

Lisa

Hunting around regarding atropine, which comes from belladona, I found this 52 year old paper. I found the bolded section interesting.

[www.ncbi.nlm.nih.gov]
286 ASSOCIATION NoTEs Canad. M. A. J.
Aug. 15, 1958, vol. 79

"It was found that small doses of atropine
are purely parasympatholytic, while much higher
doses are stimulants of the central nervous system
leading to death in convulsions. The therapeutic
safety was found to be very great, since parasympatholytic
doses do not even approach the
C.N.S. stimulant doses. The usual fatal dose of
atropine is about 100 mg. in the human, which is
about 100-200 times the therapeutic dose.
The relationship between the chemical structure"

"Potency and side effects. When the effectiveness
and side effects of each are compared, the
decision is not as easy as in the case of safety. Much
has been written about their comparative values,
and today each clinician has a pet product which
he prefers to the others. In order to decide whether
or not such an opinion is justified, two approaches
can be used. First, it is theoretically possible that
one parasympatholytic is more effective than
another, and secondly, is there experimental or
clinical evidence of such a difference? In theory,
all the tertiary amines shown in Fig. 2 act by
competition with acetylcholine at the receptors of
the parasympathetic effector cells. Having a common
mechanism of action it is difficult to believe
that they would differ, except for the dosage at
which they produce parasympathetic blocking. It
is frequently stated that one agent has fewer side
effects than another. Since all the clinical side
effects are produced by parasympathetic block,
such a statement must be qualified by adding that
any agent which produces less dryness of mouth,
blurring of vision, urinary complaints, etc., will
also produce less action on the stomach. If the
present theories on the mechanism of action of
these drugs are accepted, there is no other possibility,
unless it is postulated that the structure
of the receptors differs from organ to organ, so
that a specific affinity of one agent for a certain
organ would be possible. This, however, has never
been claimed and would be extremely difficult to
prove."

George,

Interesting form your references above to note from:

[brain.oxfordjournals.org]

That 'The mean resting vagal tone in diabetic patients was reduced by 40%'. PC always maintained that vagal AF was in some main ways the 'opposite' of diabetes.

On another note, it is of obvious concern here that anticholinergic drugs can bring about dementia than might otherwise be the case:

[www.ncbi.nlm.nih.gov]

'Findings from this study suggest that the use of medication with anticholinergic effects was associated with an increased risk of cognitive dysfunction and dementia in elderly persons. Discontinuing anticholinergic treatment was associated with a decreased risk. Medical practitioners should monitor current anticholinergic drug use in elderly patients and seek pharmacological alternatives before considering administration of neuroprotective medications to persons with MCI, thus escalating a prescription cascade involving cholinesterase inhibitors and anticholinergic drugs.'

This isn't very encouraging to those like me who are contemplating trying PB for their vagal AF!! My father died in his late 80s of multi-infarct dementia: OK, not Alzheimers as such, but even so.... Although THAT said; George also comments reasonably enough that:

"I think these are key issue to understand better:

"Those suffering from Alzheimer's disease typically have a marked shortage of acetylcholine..."

"Propantheline bromide is one of the few anticholinergics that do not cross
the blood/brain barrier"

So things look favourable that PB wouldn't speed along any potential dementia issues as one ages. George, when you say " So the idea occurred to me, "What is the least toxic, effective, vagolytic agent?", was the answer you came up with PB for the above reasons??

Ans also George, would you be kind enough to forward Dr Reiffel's papers on to me at mike@mforster.com please?

Mike

Mike,

" was the answer you came up with PB for the above reasons"

The answer is, I don't know yet. Obviously, Dr. R has had experience here.

I want to know more. My mother has dementia, too - with no real family history. Her mother lived to be 103 without much dementia. My mother has had Waldenstrom's Macroglobulinemia, a lymphoma, for 12 years. Early on she thought she correlated her decline with the chemo meds. Also, other than the cancer, which is indolent, her dementia is her problem. It is much more of one than the cancer. Mom's blood lipids and blood sugar are great.

So I'm very sensitive to the drug agent - side effect issue. Of course many of the afib agents that are commonly used have side effects, especially for chronic use. Amio being at the top of the list. Torsades de pointes being another potential side effect for many AAD's.

Though I have a technical background, it is not in the biological sciences, so it is more effort to figure this out.

To me, the vagolytic approach has much potential for vagal afibbers. However it needs careful study and is not without issues one much be aware of.

Cheers,

George

Mike,
From [brain.oxfordjournals.org]

"The amplitude of respiratory sinus arrhythmia was quantified as the ratio of the longest to the shortest R—R intervals in electrocardiograms recorded during deep inspirations and forced expirations in the supine position."

I have a bit of a problem with this protocol. The emwave device [www.heartmathstore.com] (formerly known as FreezeFramer) is based upon consciously modifying this. I've played with it and can certainly make the HRV whatever I want it to by modifying my breathing pattern.

"The frequency distribution curve of resting vagal tone was Gaussian in the controls and was also negatively correlated with age and height."

The negatively correlated with age makes sense as HVR declines with age. However in the informal survey we did 3 or 4 years ago here, most LAF males were tall. If most are vagal, this goes against the negatively correlated with height.

George