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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by gilmourr on July 9, 2012, at 16:24:11
I just restarted Nardil. Urinary retention doesn't show up until I'm on it for about a month and it takes a higher dose, but how does it happen?
It can't be increased NE. Increased NE causes smooth muscles to contract and urinary retention, but Nardil makes me have orthostatic hypotension, lower BP, and loss of energy which are all SIGNS OF LOW NE. So the urinary retention is definitely not from increased NE.
What is in a MAOI or Nardil that causes this symptom???
Posted by Phillipa on July 9, 2012, at 17:10:29
In reply to Why does Nardil cause urinary retention?, posted by gilmourr on July 9, 2012, at 16:24:11
Have you called you doc as a search claims it could be dangerous? Phillipa
Posted by Phillipa on July 9, 2012, at 17:10:35
In reply to Why does Nardil cause urinary retention?, posted by gilmourr on July 9, 2012, at 16:24:11
Have you called you doc as a search claims it could be dangerous? Phillipa
Posted by Tomatheus on July 9, 2012, at 21:00:06
In reply to Why does Nardil cause urinary retention?, posted by gilmourr on July 9, 2012, at 16:24:11
> What is in a MAOI or Nardil that causes this symptom???
Urinary retention was one of the side effects of Nardil that went away for me when I tried putting the contents of my Nardil tablets in enteric capsules. However, even when I did put the contents of my Nardil tablets into enteric capsules, there were two times when the urinary retention returned: first, when the bottles of Australian Nardil that I received from the online pharmacy I was using at the time did not have any silica gel inside of them (the bottles that I had been receiving prior to that point *did* have silica gel inside of them), and second, when I received what was most likely a bad batch of the American (Pfizer) Nardil. The fact that putting the contents of the Nardil tablets that I was taking into enteric capsules usually prevented the urinary retention from occurring, coupled with the fact that allowing my Nardil tablets to be exposed to moisture (as I did when I took the tablets from the bottles without any silica gel inside of them) brought on a return of the urinary retention, tells me that it's probably not phenelzine itself that causes urinary retention (at least not in me), but one of the byproducts of the chemical degradation of phenelzine that causes the side effect. In a post that I wrote in 2006 (http://www.dr-bob.org/babble/20060617/msgs/658844.html), I suspected that the byproduct in question might be ammonium, based on the fact that urinary retention is a known effect of ammonia toxicity. However, I don't know for certain if it is indeed ammonium (which is a byproduct of the oxidation of aqueous hydrazine) that causes urinary retention in Nardil. What I can say is that protecting the phenelzine that I took from chemical degradation (both in the stomach by putting the contents of my tablets into enteric capsules and in the pill bottles by preventing the tablets from being exposed to moisture with silica gel) seemed to prevent urinary retention from happening. At least that was the case with me.
I think that I'm sort of beating a dead horse, so to speak, by saying this, but I think that Nardil can be made to be both more effective and more tolerable than it currently is. For one thing, the coating that is used on every version of Nardil that's made in the world (at least to my knowledge) does not protect the phenelzine inside the capsules from undergoing chemical degradation in the stomach. If my reading of Gan-Lin Chen's (1986) doctoral dissertation on the degradation of phenelzine is correct, then phenelzine undergoes chemical degration some 463 times more rapidly in stomach-like conditions than in small intestine-like conditions. So, protecting phenelzine with an enteric coating is crucial to keeping phenelzine intact, which not only ensures that the phenelzine can inhibit the MAO enzymes but also prevents the phenelzine to breaking down into chemicals that may interfere with the medication's efficacy and cause unwanted side effects. Another thing is that Nardil tablets aren't always stored in conditions that protect the tablets from moisture. As I have stated in the past, when Nardil tablets are stored in excessively humid conditions (with the relative humidity being at least 80 percent), the hydrazine in the tablets undergoes rapid chemical degradation (Lovering et al., 1983). So, between the stomach and the pill bottle, there are too many opportunities for phenelzine to undergo degradation into other chemicals that may cause urinary retention and other side effects (and also contribute to a lack of effectiveness).
Tomatheus
==
REFERENCES
Chen, G.-L. (1986). The chemical kinetics of phenelzine degradation. Unpublished doctoral dissertation, University of Iowa, Iowa City.
Lovering, E. G., Matsui, F., Curran, N. M., Robertson, D. L., & Sears, R. W. (1983). Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period. Journal of Pharmaceutical Sciences, 72, 965-967. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/6620160
Posted by viper1431 on July 10, 2012, at 3:34:58
In reply to Why does Nardil cause urinary retention?, posted by gilmourr on July 9, 2012, at 16:24:11
Those are signs of other things too though, the hypotension etc are believed to be caused by the acetyl-seratonin thing rather than decreased NE.
There could be a few things that cause it, for eg increased NE and Adrenaline activating A2 receptors, that has some contracting effects on smooth muscle, as well as decreasing acetycholine which will cause things like urinary retention and dry mouth. As well as producing artery vasodilation which can lower BP.
Then you look at A1 recpetors stimulated by NE and adrenaline again and look at it's effects;
In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α1-adrenergic receptors are present in the skin, the sphincters[4] of gastrointestinal system, kidney (renal artery)[5] and brain.
Urethral sphincter
It also induces contraction of the urinary bladder[7][8], although this effect is minor compared to the relaxing effect of β2-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to delay micturition(peeing) during stress.So those are a few of the ideas i have as to why nardil can cause it.
> I just restarted Nardil. Urinary retention doesn't show up until I'm on it for about a month and it takes a higher dose, but how does it happen?
>
> It can't be increased NE. Increased NE causes smooth muscles to contract and urinary retention, but Nardil makes me have orthostatic hypotension, lower BP, and loss of energy which are all SIGNS OF LOW NE. So the urinary retention is definitely not from increased NE.
>
> What is in a MAOI or Nardil that causes this symptom???
Posted by gilmourr on July 10, 2012, at 13:52:31
In reply to Re: Why does Nardil cause urinary retention? » gilmourr, posted by Tomatheus on July 9, 2012, at 21:00:06
Interesting Tomatheus.
Do you know where I can buy enteric capsules to put Nardil in?
And since it's summer, it is very humid here. Should I put them in the fridge or something? Basement? Not really sure, but they are definitely exposed to humidity.
Posted by Tomatheus on July 10, 2012, at 17:19:56
In reply to Re: Why does Nardil cause urinary retention?, posted by gilmourr on July 10, 2012, at 13:52:31
Gilmourr,
Thank you for your reply. When I was putting the contents of the Nardil tablets that I was taking into enteric capsules, I used a product called PlasminPlus for the capsules. I ordered my PlasminPlus from herbalremedies.com and then emptied out the capsules and put the (crushed up) contents of my Nardil tablets into them. It is my understanding, however, that the PlasminPlus product may no longer be on the market. The herbalremedies.com site that I used to use says that the product has been discontinued. Another site that I came across said that the product wasn't in stock.
I did some searching on the Web and found a site called alibaba.com that appears to list several suppliers that sell empty enteric capsules, but it appears that all of the suppliers of empty enteric capsules listed on alibaba.com are based in China. Maybe somebody else here will know if there are any suppliers based in the U.S. (or perhaps somewhere like Canada, Europe, or Australia) that sell enteric capsules online, but as far as I know, there aren't any U.S.-based companies that sell empty enteric capsules on the Internet or elsewhere.
One option you might want to consider if you want to try protecting your Nardil tablets with an enteric coating is going to a compounding pharmacy. An enteric coating should not only protect the contents of Nardil tablets (the phenelzine, to be specific) from undergoing chemical degradation in the stomach, but it should also protect the phenelzine (and any hydrazine that might be in the tablets) from moisture. I would, however, think that it would be important to make sure that you bring your Nardil tablets to be compounded as soon as you get them from your pharmacy to avoid exposing the tablets to too much moisture. I know that some Nardil users who've posted on another site had some success compounding their Nardil, although I'm not sure if compounding the Nardil stopped any urinary retention that the patients may have been experiencing (compounding the medication did reportedly boost its effectiveness). I'm also not sure if the patients in question had their Nardil compounded so it would have an enteric coating or if they just had it compounded so it wouldn't dissolve as quickly. So, bringing your Nardil to a compounding pharmacy would be an experimental effort, to say the least, but I think that it might be a viable option if you really want to try an enteric-coated version of Nardil.
Although I had some success putting the contents of my Nardil tablets into enteric capsules as far as both side effects and effectiveness were concerned, I think that I should point out that my prediction that protecting Nardil with an enteric coating might help make the medication more effective and more tolerable for others is basically based on my own experimentation with different forms of the medication and the fact that many who were taking Nardil when the formulation was changed in 2003 reported a loss of effectiveness and an increased incidence of side effects after switching from the enteric-coated "old" Nardil to the film-coated "new" Nardil. So, there aren't any studies that have been conducted that show enteric-coated phenelzine to be superior to film-coated phenelzine. All of the evidence that I have to offer, as far as the effectiveness and tolerability of the various forms of Nardil are concerned, is anecdotal. However, the fact does remain that the "old" Nardil, which many long-time users of the medication found to be superior to the current version, contained pharmaceutical glaze, which both protects tablets from moisture and is used as enteric-coating material. The Nardil that's currently supplied to pharmacies in the U.S. and elsewhere does not have a coating made up of pharmaceutical glaze, and that's one of the reasons why I think that the medication isn't as effective or as tolerable for many users as it used to be.
Tomatheus
Posted by viper1431 on July 11, 2012, at 6:14:37
In reply to Re: Why does Nardil cause urinary retention?, posted by gilmourr on July 10, 2012, at 13:52:31
The nardil sold here in Australia actually contains instructions on the bottle to always store it in the fridge.
> Interesting Tomatheus.
>
> Do you know where I can buy enteric capsules to put Nardil in?
>
> And since it's summer, it is very humid here. Should I put them in the fridge or something? Basement? Not really sure, but they are definitely exposed to humidity.
Posted by Tomatheus on July 11, 2012, at 13:50:00
In reply to Re: Why does Nardil cause urinary retention? » gilmourr, posted by viper1431 on July 11, 2012, at 6:14:37
> The nardil sold here in Australia actually contains instructions on the bottle to always store it in the fridge.
Yes, the labeling information for the U.K. Nardil (http://www.medicines.org.uk/emc/medicine/18541/SPC/Nardil+tablets/) says something similar. What I'm not sure of is whether or not refrigerating Nardil would prevent it from being exposed to too much humidity. It's my understanding that some refrigerators have a high-humidity drawer and a low-humidity drawer, but I'm not sure what the relative humidity in the main area of an average refrigerator is.
To Gilmourr: It might be worth trying to refrigerate your Nardil, although I think it would be interesting to hear what a pharmacist would have to say about this matter (keep in mind that the pill bottles that store Nardil in pharmacies do have something inside of them to absorb moisture). I can't say that refrigerating your Nardil will stop the urinary retention that you're experiencing, but the fact that those taking the U.K. and Australian Nardils are instructed to refrigerate their tablets should say something.
Interestingly, Gan-Lin Chen's (1986) doctoral dissertation states that phenelzine can be stored for long periods of time "if protected from the air." It was Lovering et al. (1983) who found that the hydrazine inside phenelzine tablets undergoes rapid chemical degradation in conditions with a relative humidity of at least 80 percent. What really strikes me as interesting is that Pfizer claims to have changed Nardil's formulation because of "shelf-life issues" and that the company removed an ingredient (pharmaceutical glaze) that is known to extend the shelf life of pharmaceutical tablets. I wish that I had the answer as to what could be done to make the current version of Nardil work like the "old" version (which, according to a non-scientific survey of those affected by the formulation change, caused less urinary retention). Many measures have been taken (including some of those that I mentioned in my first post here) to try to make Nardil more effective and more tolerable, but as far as I can tell, it doesn't seem that following any of these measures led to good long-term results for anybody.
Tomatheus
==
REFERENCES
Chen, G.-L. (1986). The chemical kinetics of phenelzine degradation. Unpublished doctoral dissertation, University of Iowa, Iowa City.
Lovering, E. G., Matsui, F., Curran, N. M., Robertson, D. L., & Sears, R. W. (1983). Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period. Journal of Pharmaceutical Sciences, 72, 965-967. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/6620160
Posted by Tomatheus on July 11, 2012, at 15:26:37
In reply to Re: Why does Nardil cause urinary retention? » viper1431, posted by Tomatheus on July 11, 2012, at 13:50:00
> Many measures have been taken (including some of those that I mentioned in my first post here) to try to make Nardil more effective and more tolerable, but as far as I can tell, it doesn't seem that following any of these measures led to good long-term results for anybody.
Actually, I take that back. It's my understanding that those who tried getting their Nardil compounded noticed or are still noticing some improvements as far as the effectiveness of the medication is concerned. But as I said before, I'm not sure if getting Nardil compounded reduced the incidence of side effects like urinary retention.
Tomatheus
This is the end of the thread.
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