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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 18 to 42 of 48. Go back in thread:
Posted by BobS, on November 19, 2004, at 12:37:16
In reply to Larry?, posted by andromeda on November 19, 2004, at 9:25:43
Lar,
Do you know what causes this phenomenon, or if it is just not understood?
Regards,
BobS.
Posted by Phillipa on November 19, 2004, at 15:49:06
In reply to Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by BobS, on November 19, 2004, at 12:37:16
Same thing happened to me with Paxil, but I thought it was because I was switched to Luvox for no reason except the pDoc wanted to experiment he told me. He also put me on chloral hydrate at the same time for sleep. I was drinking beer for sleep prior to switch and had to stop drinking. Heard that chloral hydrate breaks down to acetyl alcohol in the liver so figured it acted like alcohol in my body. Any truth to this? Phillipa
Posted by jujube on November 19, 2004, at 18:20:29
In reply to Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by BobS, on November 19, 2004, at 12:37:16
I don't know what causes it, but the same thing happened to me. I went on Paxil 8.5 years ago, and had great success with it for anxiety, social phobia and depression. I went off of it for a couple of years, and when I tried it again last fall it didn't work. I had read somewhere else that apparently Paxil is a very unforgiving drug - once you ditch it, there's not going back (may not be the case for all).
Tamara
> Lar,
> Do you know what causes this phenomenon, or if it is just not understood?
> Regards,
> BobS.
>
Posted by Phillipa on November 19, 2004, at 19:28:31
In reply to Re: Back to Paxil? 1st time worked fine, 2nd nada Lar » BobS,, posted by jujube on November 19, 2004, at 18:20:29
Lar, A lot of messages out there that need your expertice.
Posted by stresser on November 19, 2004, at 20:14:53
In reply to Re: Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by Phillipa on November 19, 2004, at 19:28:31
Larry,
I really only meant that intimidating comment as a compliment,I'm sorry if I offended you, I didn't want that to happen. I value having you on the board and consider it a privilage. I don't seem to have much of a reaction to any anti-depressants, or at least the different medications I have tried. I do have a question concerning accutane, because I and my daughter have taken it in the past. Let me tell you exactly what has happened. My daughter took Accutane three years ago, and it worked very well....until she stopped taking it. Her face broke out about three months after she she took her last pill, so the doc. put her on another round. I have ALWAYS had trouble with acne, and at 41, (at that time) was tired of the oily face and teenage break-outs. I decided to take it also, and he put us both on the generic form of accutane. Seven months on the generic form went very well, and we both went off with great results and very little side-effects. Some depression, but that was there anyway, so who knows about that one. It was probably six months after we both went off the generic, that she started to break-out horribly AGAIN, and after anti-biotics and Retin A once agian, she is back on the real Accutan, and taking one pill twice per week. That is keeping her acne under some control, but if she lets off, it returns like chicken pox! She did take many anti-biotics and nothing worked for her. Myself, the oily skin is back, and I am having those nasty break-outs and wonder if the generic was worth my trip to the pharmacy. Honestly, I don't think my body responds to medication very well, and I think I have passed it on to my daughter. Is that possible? Have we just always taken the wrong medications for our bodies? What is your opinion? -L
Posted by Phillipa on November 19, 2004, at 22:12:58
In reply to Larry: What is your opinion on accutane?, posted by stresser on November 19, 2004, at 20:14:53
Larry, I hope we haven't scared you off with our questions. If nothing else, this should help your depression that so many people have so much respect for your vast knowledge! Don't leave us please! Phillipa
Posted by jasmineneroli on November 20, 2004, at 0:11:20
In reply to Re: Larry: What is your opinion on accutane?, posted by Phillipa on November 19, 2004, at 22:12:58
..........Can't a guy get a day off, now & then??
I'm sure he'll be back with his usual interesting and thought provoking posts and try to answer some of our questions when he has time!
Take care, Lar!
Jas
Posted by stresser on November 20, 2004, at 14:23:15
In reply to Hey PPL- it's only 1 day since Larry posted......., posted by jasmineneroli on November 20, 2004, at 0:11:20
This is true....we find a guy that can help us and don't realize that he too, needs some time away. He is truly a "gem" to all of us. -L
Posted by Larry Hoover on November 21, 2004, at 9:01:25
In reply to Re: How do I know IF I am a slow metabolizer?, posted by jasmineneroli on November 19, 2004, at 1:55:14
> Lar:
> This is absolutely fascinating! I'm s'posed to be in bed, loaded up with Tryptophan and snoozing straight throught the night!! But it's just got my mind racing. So many questions.
>
> I'm perplexed over apparent contradictions.
> According to the tables, Buspirone uses 3A4 only.
> Buspirone didn't work for me at all and gave me my usual side effects. Clonazepam works like a hot dam, with no side effects -3A4 only, too! Must be other factors at work here?Indeed there are. Let's not forget that a drug has specific effects. The liver enzyme thing is about how your body disposes of medication, not so much about how the medication works. There is one factor to consider, vis a vis liver transformation of meds. Some drugs have active metabolites. That means that after the liver transorms the drug, it has specific drug activity in that new form. Diazepam (Valium) has four active metabolites (if I recall correctly).
Ordinarily, the liver effects mediate side effects. The things that you don't want the drug to do, but that are a natural response to the drug, nonetheless.
> On the other hand, I believe myself to be unable to tolerate any form of progesterone (2C19 & 3A4)and even low doses of Citalopram give me s/e's (2C19). However, both have a powerful effect on me. (I only need low dose to have a response).So does that mean I'm a good metabolizer of 2C19, or a bad one? (Big effect vs Bad side effects?).
That suggests that you are a poor metabolizer at 2C19. Poor metabolizers maintain high plasma concentration for a longer period. The drug breaks down more slowly than it is expected to (i.e. it has an extended half-life) so that if you take it recurrently as prescribed, the blood concentration can increase to levels far above those anticipated by the doctor who prescribed it. For poor metabolizers, achieving stable therapeutic blood concentrations of a med can take a fraction of the normal dose.
> I've had good (effective) responses to both codeine and DM (both 2D6 and 3A4). However, higher doses of codeine give me stomach side effects. I think 3A4 has something to do with gastric side effects???
Good responses, at normal doses? That suggests that you're in the midground of 2D6 function. If you exceed the capacity of 2D6 (as by overdose) it can't work any faster than its maximum rate. That leaves more of the drug around for all the side-effects to occur. Codeine binds to receptors in the gut that regulate peristalsis, so the rhythmic contractions of the gut that propel food through the intestines are dampened. You get severely constipated. For others, those same receptor effects cause the muscles to spasm, and you get violent nausea.
> Ibuprofen has little analgesic effect for me, so does that indicate poor metabolism of 2C9?
Poor metabolism at an enzyme is normally indicated by an exaggerated drug effect. There is probably something else that makes ibuprofen ineffective in your body.
> Acetaminophen has little effect too, except in high doses(1A2, 2E1 & 3A4 again).
Acetominophen is a strange drug. It works indirectly to cause analgesia. It's a tricky drug to understand.
> Since caffeine does work quickly (1A2 & 3A4) should I assume that the 2E1 in acetaminophen is not being metabolized properly???
Again, let's not confuse liver effects with drug effects. Caffeine drugs your brain effectively. That's what you're noticing.
> The tables weren't detailed enough to show interactions between my particular drugs and I'd like to know which enzymes are inhibited/induced by Tryptophan. Do you know another source of info??
I don't know of any resource that would give you that information. I'll take a look around.
> In fact, I have been recently thinking, that I'm extremely sensitive to MOST drugs EXCEPT analgesics and hypnotics. (I always need loads of novacaine for numbing, higher sleeping pill doses than the norm, lot's of acetaminophen for pain). I was wondering why. Maybe this CP450 puzzle holds the answer!
Maybe. It's a piece of the puzzle, the puzzle of the unique person. Your body is not a statistical entity. Just because the doctor predicts that dose X of drug Y will produce effect of magnitude Z does not have any bearing whatsoever on what will really happen inside you. Doctors seldom think about that, so we have to. When we do the experiment, we have to note what happens. Hopefully, the doctors listen when we report the outcomes of the experiment.
Seriously, the lack of effect of hypnotics or pain meds could be due to effects mediated by magnesium deficiency, or another thing my brain just isn't pulling into consciousness.
> and Larry, I really do think you should write a book. You have an excellent writing style - varied vocab. etc.etc. :)
> Take care
> JasI should write a book. I should write a book. I should write a book.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:06:57
In reply to Re: How do I know IF I am a slow metabolizer? » jasmineneroli, posted by gromit on November 19, 2004, at 1:59:33
> Maybe this explains why codeine does nothing for me, but vicodin is a stimulant. So much to learn, so little remaining brain cells.
>
> RickA critical clue, perhaps. If codeine doesn't work for you, you fall into a group of perhaps even 10% of us, who have trouble with 2D6 drugs. As about one third of all psychotropic meds are at least partially metabolized by 2D6, that's a big problem. If you're innately weak in 2D6, and you take a drug that shuts down (inhibits) 3A4, you can have horrid reactions. Honestly, I think that's why Serzone (nefazodone) can be hepatotoxic.
Knowing I get no pain relief from codeine, I constantly run into problems if I need acute pain treatment and doctors think I'm drug-seeking. But such is life. I calmly explain that codeine does nothing but constipate me, and I need a different opiate. No tylenol 3's for me.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:11:29
In reply to Larry?, posted by andromeda on November 19, 2004, at 9:25:43
I don't know enough about phenelzine to answer your question. Some people do better with a slower dose titration. What that means is you wait until the side effects subside at a particular dose level before you escalate. Rather than reducing the dose from 15 mg, you just stay at that level until you feel that it is possible to increase the dose.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:12:19
In reply to Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by BobS, on November 19, 2004, at 12:37:16
> Lar,
> Do you know what causes this phenomenon, or if it is just not understood?
> Regards,
> BobS.
>I've never seen a good explanation as to why it is like this, but it surely is a real phenomenon.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:15:35
In reply to Re: Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by Phillipa on November 19, 2004, at 15:49:06
> Same thing happened to me with Paxil, but I thought it was because I was switched to Luvox for no reason except the pDoc wanted to experiment he told me. He also put me on chloral hydrate at the same time for sleep. I was drinking beer for sleep prior to switch and had to stop drinking. Heard that chloral hydrate breaks down to acetyl alcohol in the liver so figured it acted like alcohol in my body. Any truth to this? Phillipa
The principle metabolite is trichloroethanol. It probably puts the same liver enzymes under stress as does ethanol itself. Definitely not a good combination, in any case, because of the depressant effects of both drugs. You might stop breathing on the combination, if the doses were high enough.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:17:11
In reply to Re: Back to Paxil? 1st time worked fine, 2nd nada Lar, posted by Phillipa on November 19, 2004, at 19:28:31
> Lar, A lot of messages out there that need your expertice.
Sorry for my untimely absence, but I was doing a workshop on advocacy for homeless and poor people. I'm the legal geek for that.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:25:43
In reply to Larry: What is your opinion on accutane?, posted by stresser on November 19, 2004, at 20:14:53
> Larry,
> I really only meant that intimidating comment as a compliment,I'm sorry if I offended you, I didn't want that to happen. I value having you on the board and consider it a privilage.Thank you for your kind words, and apology. I wasn't offended. I know I intimidate without ever meaning to. Trust me to work through things with you, okay? Just keep asking questions, and I'll try and answer them to your satisfaction.
> I don't seem to have much of a reaction to any anti-depressants, or at least the different medications I have tried.
If you also mean no side-effects, too, you may be a rapid metabolizer. That's quite the opposite effect to most of the people who entered into this thread. You might deactivate and excrete the drug so fast that is has no chance of accumulating in your blood to effective levels. If you can get a doctor to consider helping you (it would take some direct supervision and probably some fairly expensive bloodwork), you might find that purposely using a liver enzyme inhibitor would enhance the drug effect. For example, ketoconazole, the antifungal drug, near totally inhibits 3A4. Maybe that's the kind of thing you need, along with an antidepressant, to get some effect.
Also, you might consider St. John's wort. It works by many different and unique mechanisms that may not be affected by your liver function.
> I do have a question concerning accutane, because I and my daughter have taken it in the past. Let me tell you exactly what has happened. My daughter took Accutane three years ago, and it worked very well....until she stopped taking it. Her face broke out about three months after she she took her last pill, so the doc. put her on another round. I have ALWAYS had trouble with acne, and at 41, (at that time) was tired of the oily face and teenage break-outs. I decided to take it also, and he put us both on the generic form of accutane. Seven months on the generic form went very well, and we both went off with great results and very little side-effects. Some depression, but that was there anyway, so who knows about that one. It was probably six months after we both went off the generic, that she started to break-out horribly AGAIN, and after anti-biotics and Retin A once agian, she is back on the real Accutan, and taking one pill twice per week. That is keeping her acne under some control, but if she lets off, it returns like chicken pox! She did take many anti-biotics and nothing worked for her. Myself, the oily skin is back, and I am having those nasty break-outs and wonder if the generic was worth my trip to the pharmacy. Honestly, I don't think my body responds to medication very well, and I think I have passed it on to my daughter. Is that possible? Have we just always taken the wrong medications for our bodies? What is your opinion? -L
Accutane is due for some serious attention. It can be very toxic in some people. That aside, the fact that it works so well for you suggests that you might consider just using it until after menopause. That should end the problem for you. I'd have to look more closely at how it works. I'm not really sure.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:26:12
In reply to Re: Larry: What is your opinion on accutane?, posted by Phillipa on November 19, 2004, at 22:12:58
> Larry, I hope we haven't scared you off with our questions. If nothing else, this should help your depression that so many people have so much respect for your vast knowledge! Don't leave us please! Phillipa
Just busy. Not gone.
Lar
Posted by Larry Hoover on November 21, 2004, at 9:27:07
In reply to Hey PPL- it's only 1 day since Larry posted......., posted by jasmineneroli on November 20, 2004, at 0:11:20
> ..........Can't a guy get a day off, now & then??
Thanks. Ummm, wanna help me write a book? <teasing>
Lar
Posted by gromit on November 21, 2004, at 9:29:12
In reply to Re: How do I know IF I am a slow metabolizer? » gromit, posted by Larry Hoover on November 21, 2004, at 9:06:57
Thanks Larry, when you post you don't mess around do you?
Posted by Larry Hoover on November 21, 2004, at 11:55:50
In reply to Re: How do I know IF I am a slow metabolizer? » Larry Hoover, posted by gromit on November 21, 2004, at 9:29:12
> Thanks Larry, when you post you don't mess around do you?
I should mess around? <Spock eyebrow>
Just think of me as a capacitor, and this as my discharge.
Lar
Posted by jasmineneroli on November 22, 2004, at 0:30:19
In reply to Re: How do I know IF I am a slow metabolizer? » jasmineneroli, posted by Larry Hoover on November 21, 2004, at 9:01:25
Thanks V. much for the info, Lar.
Ha! it must've been a shock to come back to Babble and find all this waiting for you???
Anyway, in regard to myself, I've had another
a-ha moment. I discovered that the drug I had the stongest s/e reaction to (Moclobemide) is also a 2C19. That is the common denominator in my 3 worst drug reactions (all with the same symptoms). Now I know I can never take any drug that uses that enzyme in hepatic metabolism.
That is hugely helpful! I don't really care if I'm just a slow metabolizer or I simply don't have the enzyme present. I will avoid all 2C19 drugs!
I'm trying to search for info on tryptophan, but only find the hepatic enzyme named tryptophan pyrrolase, which is an enzyme specific to tryptophan and not part of the P450 clan! I will keep looking. I suspect P450 is not involved at all. The reason why I'm wondering about tryptophan is I've been feeling "unwell" lately and wonder, if this is culprit. Sleep and mood have improved, so I hope it's something else!
Thanks for being you!!!!
Jas
Posted by jasmineneroli on November 22, 2004, at 0:32:47
In reply to Re: Hey PPL- it's only 1 day since Larry posted....... » jasmineneroli, posted by Larry Hoover on November 21, 2004, at 9:27:07
> > ..........Can't a guy get a day off, now & then??
>
> Thanks. Ummm, wanna help me write a book? <teasing>
>
> LarHa! Well, maybe I could design the cover or something..............or go get coffee/donuts?
Jas
Posted by Larry Hoover on November 22, 2004, at 7:36:30
In reply to Re: How do I know IF I am a slow metabolizer? » Larry Hoover, posted by jasmineneroli on November 22, 2004, at 0:30:19
> Thanks V. much for the info, Lar.
> Ha! it must've been a shock to come back to Babble and find all this waiting for you???
> Anyway, in regard to myself, I've had another
> a-ha moment. I discovered that the drug I had the stongest s/e reaction to (Moclobemide) is also a 2C19. That is the common denominator in my 3 worst drug reactions (all with the same symptoms). Now I know I can never take any drug that uses that enzyme in hepatic metabolism.Here's the nitty-gritty on 2C19... The gene variants are designated as *X in the following quote: "*2 .. *8 : inactive (in up to 20% of Asians {*2 and *3}, 3% of Caucasians, 19% of African Americans, 8% of Africans, up to 71% of Pacific islanders )."
What that means is that there are a number of null genes for 2C19, ones that don't work at all, and they're quite common in certain populations.
> That is hugely helpful! I don't really care if I'm just a slow metabolizer or I simply don't have the enzyme present. I will avoid all 2C19 drugs!
If you want to take a look at a somewhat quirky but information-packed site, take a look at:
http://www.anaesthetist.com/physiol/basics/metabol/cyp/cyp.htm#alphaIf you click on a drug name, it summarizes everything in one place. If you click on an enzyme, though, it gives you an amazingly detailed analysis of what is known about that enzyme. Just looking at 2D6 for example, it lists a couple of dozen different allelic variants (the different gene types for this enzyme), and their different activity levels. Pretty cool.
> I'm trying to search for info on tryptophan, but only find the hepatic enzyme named tryptophan pyrrolase, which is an enzyme specific to tryptophan and not part of the P450 clan! I will keep looking. I suspect P450 is not involved at all. The reason why I'm wondering about tryptophan is I've been feeling "unwell" lately and wonder, if this is culprit. Sleep and mood have improved, so I hope it's something else!
Something else, would be my guess. One way to look at tweaking a nutrient intake is to think of the body as something like a baby's mobile. You know those things with different objects hanging down on strings?.....you move one piece, and they all move? I think we're a bit like that.
> Thanks for being you!!!!
> JasAwww, shucks. <grin>
Lar
Posted by stresser on November 22, 2004, at 15:51:44
In reply to Re: Larry: What is your opinion on accutane? » stresser, posted by Larry Hoover on November 21, 2004, at 9:25:43
Larry,
The Accutane only works when I am on it. -L
Posted by jasmineneroli on November 23, 2004, at 0:49:24
In reply to Re: How do I know IF I am a slow metabolizer? » jasmineneroli, posted by Larry Hoover on November 22, 2004, at 7:36:30
Hey Lar!
EXTREMELY cool link! I think I've found a new obsession! (J/K)
Well, I think I've discovered the reason why I'm a slow metabolizer of 2C19........oral contraceptive pill use for 5 years in the mid 1970's! (And subsequent contraceptive use in an attempt to mitigate peri-menopause symptoms).Since they inhibit 2C19, do you think it's possible that inhibition of an enzyme for a long period of time by a certain drug or group of drugs (particularly the "old" high dose Oral Contraceptives) permanently effects the enzymes' abiilty to metabolize efficiently, or at all? I did notice that a couple of notes on other isoenzymes on the table, stating "irreverseable effect".
I think this theory may well apply to me. It's also interesting to note that I didn't develop any irritable depression until I took O.C.'s ( always had anxiety, tho'). So much so, that I was really hesitant to take them again to help perimenopause. After that experiment with them, and horrible suicidal depression/anxiety, even my GP of the time said " I think I've made you sick, by putting you back on the pill"!
There has to be a connection between it all.
For some reason, I'm finding this unravelling process, very therapeutic. I feel like I'm finding answers to "why am I like this?" and "why do I keep responding so badly with the same S/E's?". It's kinda empowering. I just don't want to keep on trying drug after drug and having the same ill-effects. At least I will know which ones I definitely shouldn't try.
Thanks so very much Larry :).
Warm wishes, Jas
PS
Still working on the tryptophan plan.
Posted by jasmineneroli on November 23, 2004, at 0:51:07
In reply to How do I know IF I am a slow metabolizer?, posted by ZenTen on November 17, 2004, at 12:17:12
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