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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 35 to 59 of 59. Go back in thread:
Posted by Dr. Bob on March 11, 2006, at 10:45:21
In reply to Re: The 'new' NardilThanks Willyee » forgetful mary, posted by ed_uk on March 10, 2006, at 15:04:12
> I find your post offensive.
> I'm not the one who's being rude.
Please don't post anything that could lead others to feel accused or put down. Even if you feel accused or put down yourself. Two wrongs don't make a right.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Also, for a nice clarification of what constitutes an I-statement, please see:
http://www.dr-bob.org/babble/admin/20040112/msgs/320097.html
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above posts, should of course themselves be civil.
Thanks,
Bob
Posted by Dr. Bob on March 11, 2006, at 10:48:09
In reply to Re: Changing the formulation » ed_uk, posted by Last Chance on March 10, 2006, at 20:34:17
> Do you always need to have the last word?
Please don't jump to conclusions about others or post anything that could lead them to feel accused or put down.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above post, should of course themselves be civil.
Thanks,
Bob
Posted by Michael Bell on March 11, 2006, at 11:41:38
In reply to Bioequivalence, posted by ed_uk on March 8, 2006, at 16:05:06
But that's exactly the problem. Bioequivalency only discusses the absorption rate of the drug into the bloodstream, NOT the rate and completeness of the absorbtio at the site of action. This is the whole reason that the FDA has recognized that there are major problems with the guidelines for bioequivlency, because it may not equal thereapeutic equivalency.
Acording to the FDA, for a drug to be bioequivalent, it must. "deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug"
However, what happens to the drug after it enters the bloodstream is not assessed. How well is it absorbed at the site of action, which in this case is mainly the small intestine.
The FDA equates bioequivalence with therapeutic equivalence, but the Dept. of Pharmaceutics and Pharamaceutical chemistry noted that this leaves out major important determining factors, by stating:
"It is important to note that the FDA designation of thera-peutic equivalence does not consider several formulation char-acteristics, including packaging, scoring configuration, shape, or pharmaceutical excipients (e.g., colors, preservatives, fla-vors)."
The theory has always been that the new nardil is not being absorbed as well at the site of action of the drug.
> In order for the 'new' Nardil formulation to be approved, it would have had to have been shown to be bioequivalent to the 'old' formulation.
>
> Excipients can affect the rate and extent of absorption of a drug. Two formulations are considered to be bioequivalent when their absorption parameters are the same.
>
> Ed
Posted by ed_uk on March 11, 2006, at 13:03:58
In reply to Re: Changing the formulation » ed_uk, posted by Last Chance on March 10, 2006, at 20:34:17
Who are you?
Ed
Posted by ed_uk on March 11, 2006, at 13:07:30
In reply to Re: please be civil » ed_uk, posted by Dr. Bob on March 11, 2006, at 10:45:21
Hi Bob
>Please don't post anything that could lead others to feel accused or put down. Even if you feel accused or put down yourself. Two wrongs don't make a right.
I don't think I did anything wrong. Forgetful Mary stated that I was arrogant and ignorant, which was, frankly, rude.
Regards
Ed
Posted by ed_uk on March 11, 2006, at 13:08:51
In reply to Re: Changing the formulation, posted by SLS on March 11, 2006, at 6:50:36
Hi Scott
>I am not concerned that there will be a lack of efficacy due to a change in formulation. However, I will be prepared to take a higher dosage if necessary so as to offset any change in bioavailability that may exist.
Good idea.
Regards
Ed
Posted by ed_uk on March 11, 2006, at 13:17:42
In reply to And that's the problem » ed_uk, posted by Michael Bell on March 11, 2006, at 11:41:38
Hi M
>Bioequivalency only discusses the absorption rate of the drug into the bloodstream, NOT the rate and completeness of the absorbtio at the site of action.
Phenelzine exerts its antidepressant and anxiolytic efficacy by acting on the brain. Its 'site of action' is the brain, not the intestine.
>However, what happens to the drug after it enters the bloodstream is not assessed.
Excipients do not affect the pharmacological properties of a drug molecule once it reaches the blood stream.
>The theory has always been that the new nardil is not being absorbed as well at the site of action of the drug.
That doesn't make sense to me. Phenelzine's site of action is the brain. The excipients do not influence the ease at which the drug can cross the blood-brain barrier.
Regards
Ed
Posted by ed_uk on March 11, 2006, at 13:21:00
In reply to Re: Changing the formulation, posted by SLS on March 11, 2006, at 6:50:36
Hi Scott
>I am not concerned that there will be a lack of efficacy due to a change in formulation. However, I will be prepared to take a higher dosage if necessary so as to offset any change in bioavailability that may exist.
Anyone who is encountering problems with the new formulation should be willing to adjust the size, timing and frequency of doses. If they are not willing to do this, they are effectively shooting themself in the foot!
Kind regards
Ed
Posted by forgetful mary on March 11, 2006, at 20:45:35
In reply to Re: please be civil » Dr. Bob, posted by ed_uk on March 11, 2006, at 13:07:30
The truth shall set you free!!!
> Hi Bob
>
> >Please don't post anything that could lead others to feel accused or put down. Even if you feel accused or put down yourself. Two wrongs don't make a right.
>
> I don't think I did anything wrong. Forgetful Mary stated that I was arrogant and ignorant, which was, frankly, rude.
>
> Regards
>
> Ed
Posted by forgetful mary on March 11, 2006, at 20:49:51
In reply to Re: Changing the formulation » SLS, posted by ed_uk on March 11, 2006, at 13:21:00
If I step outside and it is raining, I don't really need to know why it is raining to get wet....Maybe I should ask ??
Hey Ed, do I need an umbrella?????LOL> Hi Scott
>
> >I am not concerned that there will be a lack of efficacy due to a change in formulation. However, I will be prepared to take a higher dosage if necessary so as to offset any change in bioavailability that may exist.
>
> Anyone who is encountering problems with the new formulation should be willing to adjust the size, timing and frequency of doses. If they are not willing to do this, they are effectively shooting themself in the foot!
>
> Kind regards
>
> Ed
>
Posted by linkadge on March 11, 2006, at 21:31:10
In reply to A post for Linkadge, posted by ed_uk on March 9, 2006, at 13:14:48
I know what you're saying.
You know more than I in terms of how the formulations might act the same or differently.
I agree with the logic.
You are describing what I call the "retrograde control" game.
This is basically where somebody changes details or interpretations of the past to make it seem as if it was a situation that they had "controll over" all the time.
For instance, I failed a test. I reframe that into, I failed because I was on the wrong drugs, not, I failed because I am dumb.
But, in the end, my lie serves its purpose in that so long as it gives me courage to try things again, eventually I will pass.
In this case, I don't know. I remember that at one point, a lot of people were complaining about a new lithium formulation. Nobody believed them, but it turned out that this preparation did not contain the indicated content, and got pulled.
So, if the drug is as claimed, then it is probably more in people's mind, but in the possability that the drug is actually an inferior formulation for whatever reason, then maybe there is something to it.
I know what you are saying, but don't really know enough to have any valid opinion.
Linkadge
Posted by Michael Bell on March 12, 2006, at 3:26:41
In reply to Re: And that's the problem » Michael Bell, posted by ed_uk on March 11, 2006, at 13:17:42
Hey Ed,
Most Mao-A, which has more of an antidepressant than Mao-B, is found in the intestine, liver and gut area. Mao-B, on the other hand, like what deprenyl causes inhibition of at low doses, is found mainly in the brain (despite what the smart-drugs website claims). Nardil's main site of action is in the small intestine, NOT the brain.
> Hi M
>
> >Bioequivalency only discusses the absorption rate of the drug into the bloodstream, NOT the rate and completeness of the absorbtio at the site of action.
>
> Phenelzine exerts its antidepressant and anxiolytic efficacy by acting on the brain. Its 'site of action' is the brain, not the intestine.
>
> >However, what happens to the drug after it enters the bloodstream is not assessed.
>
> Excipients do not affect the pharmacological properties of a drug molecule once it reaches the blood stream.
>
> >The theory has always been that the new nardil is not being absorbed as well at the site of action of the drug.
>
> That doesn't make sense to me. Phenelzine's site of action is the brain. The excipients do not influence the ease at which the drug can cross the blood-brain barrier.
> Regards
>
> Ed
>
>
>
>
Posted by ed_uk on March 12, 2006, at 9:46:28
In reply to No, the main site of action is not the brain » ed_uk, posted by Michael Bell on March 12, 2006, at 3:26:41
Hi Michael
>Most Mao-A, which has more of an antidepressant than Mao-B, is found in the intestine, liver and gut area. Mao-B, on the other hand, like what deprenyl causes inhibition of at low doses, is found mainly in the brain (despite what the smart-drugs website claims). Nardil's main site of action is in the small intestine, NOT the brain.
Phenelzine acts an an antidepressant and anxiolytic by acting on the brain, not the small intestine. Although MAO-A is undoubtedly present in the intestine, inhibiting this enzyme does not result in antidepressant efficacy.
MAO is present in the intestine because it is needed to metabolise dietary tyramine. Drugs which inhibit intestinal MAO allow large amounts of tyramine to enter the blood stream, potentially resulting in a hypertensive crisis.
MAO-A and MAO-B is present in the brain to metabolise various neurotransmitters eg. serotonin etc. Inhibition of MAO-A and MAO-B in the brain potentiates the activity of these neurotransmitter systems and results in an antidepressant/anxiolytic effect.
If it were possible to administer phenelzine transdermally (as a skin patch), it would remain and effective AD because it would still inhibit MAO-A and MAO-B in the brain. The risk of hypertensive crisis would be reduced because there would be less inhibition of MAO in the intestine.
In summary, phenelzine inhibitits MAO in the intestine, but this is an unwanted effect, it does not result in any antidepressant efficacy. Phenelzine acts an an AD by inhibiting MAO-A and MAO-B in the brain.
>Most Mao-A, which has more of an antidepressant than Mao-B, is found in the intestine, liver and gut area. Mao-B, on the other hand, like what deprenyl causes inhibition of at low doses, is found mainly in the brain (despite what the smart-drugs website claims).
MAO-A and MAO-B are both present in the brain. That large quantities of MAO-A are found in the intestine is not relevent to phenelzine's efficacy. Phenelzine is a more consistently effective AD then selegiline (deprenyl) because it is non-selective ie. it readily inhibits both forms of MAO in the brain. You are correct that phenelzine inhibits MAO in the gut, but this is not responsible for its antidepressant efficacy. It is, in fact, an unwanted effect because it increases the likelihood of suffering a hypertensive crisis.
An ideal MAOI antidepressant would potently inhibit both MAO-A and MAO-B in the brain without affecting MAO enzymes in the intestine.
All antidepressant owe their efficacy to their actions on the brain. It is the brain which is responsible for our depression and anxiety. Like phenelzine, many ADs act on other parts of the body - this is responsible for many of their side effects. The TCAs are particularly notorious for this because they block the effect of acetylcholine (ie. they are anticholinergic) in many organ systems.
SSRIs also act on the intestine, this may result in diarrhea, abdo pain or constipation. It is often said that there is more serotonin in the intestine than in the brain. This does not mean that SSRIs are effective ADs due to their actions on the intestine! SSRIs also act on the platelets in the blood. Neither of these properties results in AD efficacy. Like phenelzine, the SSRIs act as antidepressants by acting on the brain. Their other actions are unwanted. It is very difficult to synthesise brain-selective drugs! Most psych drugs interfere with intestinal activity, but this is not responsible for their efficacy in mental health problems! All psych drugs owe their efficacy to their actions on the brain.
Phenelzine inhibits MAO-A in the brain. This is one of its most important effects in the treatment of depression and anxiety.
Regards
Ed
Posted by ed_uk on March 12, 2006, at 9:51:33
In reply to Re: A post for Linkadge, posted by linkadge on March 11, 2006, at 21:31:10
>For instance, I failed a test. I reframe that into, I failed because I was on the wrong drugs, not, I failed because I am dumb.
You're certainly not dumb Link :) Thanks for posting!
Ed
Posted by linkadge on March 12, 2006, at 15:19:36
In reply to Re: A post for Linkadge » linkadge, posted by ed_uk on March 12, 2006, at 9:51:33
Well, I guess I mean that it is possable for bad things to happen which are out of our controll, and were never in our controll.
Linkadge
Posted by Last Chance on March 12, 2006, at 15:27:31
In reply to Re: Changing the formulation » Last Chance, posted by ed_uk on March 11, 2006, at 13:03:58
> Who are you?
>
> EdHello Ed - Could you be a little more specific about what you would like to know about me. I am a former user of Nardil (old formula). I have been following this board for a long time, but do not post very often. As you noticed, I was reprimanded for the post I made to you. I don't have anything else, really, to say about how I perceive your posts, attitudes re: old and new Nardil, for I would like to keep in good standing here and be able to post when I feel the need. Richard
Posted by ed_uk on March 12, 2006, at 17:26:48
In reply to Re: Changing the formulation, posted by Last Chance on March 12, 2006, at 15:27:31
Hi
>Hello Ed - Could you be a little more specific about what you would like to know about me.
I was just wondering why you suddenly joined the thread with your rather unkind (I thought) post directed at me.
>I don't have anything else, really, to say about how I perceive your posts, attitudes re: old and new Nardil, for I would like to keep in good standing here and be able to post when I feel the need.
It seems that that's what it's like here at babble ie. you can only say certain things or else people get angry and dislike you. I am disappointed at how people have reacted to my thread, particularly considering that I am a long term poster who has given advice to many people.
Ed
Posted by notfred on March 12, 2006, at 23:47:59
In reply to Adjusting the dose, posted by ed_uk on March 9, 2006, at 18:09:50
"Some of the symptoms people have reported when transitioning from the 'old' Nardil to the 'new' Nardil resemble withdrawal symptoms. It is possible that the new formulation may have resulted in slightly lower bioavailability. If this is true, increasing the dose or frequency of administration should help. Why is no one discussing this? The 'new' Nardil is all we have. We must learn to optimise its efficacy and usefulness, rather than dismissing it as useless."
Given how simple it is to counter the alleged difference between the old and new Nardil, namely taking a bit more Nardil, I do not think all this is really about the new Nardil. There is a different agenda here.
Posted by Last Chance on March 13, 2006, at 2:18:34
In reply to Re: Changing the formulation » Last Chance, posted by ed_uk on March 12, 2006, at 17:26:48
> Hi
>
> >Hello Ed - Could you be a little more specific about what you would like to know about me.
>
> I was just wondering why you suddenly joined the thread with your rather unkind (I thought) post directed at me.
>
> >I don't have anything else, really, to say about how I perceive your posts, attitudes re: old and new Nardil, for I would like to keep in good standing here and be able to post when I feel the need.
>
> It seems that that's what it's like here at babble ie. you can only say certain things or else people get angry and dislike you. I am disappointed at how people have reacted to my thread, particularly considering that I am a long term poster who has given advice to many people.
>
> EdHi Ed - I wasn't angry - it just felt like there were these differences of opinion going on, and no one seemed to be content to just make their point once - I suppose I aimed my criticism at you because I disagreed with what you were saying. I didn't express it in the best way, for sure, and I apologize for that. Richard
Posted by ed_uk on March 13, 2006, at 13:11:15
In reply to Re: Adjusting the dose, posted by notfred on March 12, 2006, at 23:47:59
Hi NF :)
>Given how simple it is to counter the alleged difference between the old and new Nardil, namely taking a bit more Nardil, I do not think all this is really about the new Nardil. There is a different agenda here.
What do you mean?
Regards
Ed
Posted by ed_uk on March 13, 2006, at 13:13:18
In reply to Re: Changing the formulation, posted by Last Chance on March 13, 2006, at 2:18:34
Hi R
I'm sorry if I upset you.
Ed
Posted by forgetful mary on March 13, 2006, at 19:02:25
In reply to Re: Adjusting the dose, posted by notfred on March 12, 2006, at 23:47:59
It is not that easy....increasing the dose does not work for everyone, and still is inefficient. Or should I say "allegedly" inefficient. I for one am not saying the new nardil is useless. I have said it is better than SSRI's and better than nothing, but still not as good as it was. What "agenda" are you referring to ??
Gimme my old Nardil and I needn't even post on this board. Your assumption is wrong and insulting. Only those who tried the old Nardil know what I am talking about and are able to comment on the difference. Any other opinions are merely suppositions and should be treated as such....> "Some of the symptoms people have reported when transitioning from the 'old' Nardil to the 'new' Nardil resemble withdrawal symptoms. It is possible that the new formulation may have resulted in slightly lower bioavailability. If this is true, increasing the dose or frequency of administration should help. Why is no one discussing this? The 'new' Nardil is all we have. We must learn to optimise its efficacy and usefulness, rather than dismissing it as useless."
>
>
> Given how simple it is to counter the alleged difference between the old and new Nardil, namely taking a bit more Nardil, I do not think all this is really about the new Nardil. There is a different agenda here.
Posted by Dr. Bob on March 13, 2006, at 20:27:49
In reply to Re: Changing the formulation » Last Chance, posted by ed_uk on March 12, 2006, at 17:26:48
> your rather unkind (I thought) post
Please don't post anything that could lead others to feel accused or put down. I just asked you to be civil, so now I'm going to block you from posting for a week.
But please don't take this personally, this doesn't mean I don't like you or think you're a bad person.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above posts, should of course themselves be civil. Thanks.
> It seems that that's what it's like here at babble ie. you can only say certain things or else people get angry and dislike you. I am disappointed at how people have reacted to my thread, particularly considering that I am a long term poster who has given advice to many people.
I'm sure people appreciate the help you've so generously offered, but still it can be hard to swim against the tide. Hope to see you back in a week,
Bob
Posted by gardenergirl on March 14, 2006, at 17:50:48
In reply to Re: Adjusting the dose, posted by forgetful mary on March 13, 2006, at 19:02:25
> Your assumption is wrong and insulting.
Please don't post anything that could lead others to feel accused or put down. I asked you to be civil before, so now I am blocking you from posting for one week.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues, as well as replies to the above post, should be directed to Admin and should of course themselves be civil.
Regards,
gg acting as deputy for Dr. Bob
Posted by Phillipa on March 14, 2006, at 20:01:48
In reply to Blocked for a week » forgetful mary, posted by gardenergirl on March 14, 2006, at 17:50:48
I personally have never taken nardil but we have a fairly frequent poster named ACE who swears that tht new Naril is his miracle med. Fondly, Phillipa
This is the end of the thread.
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