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Dr. Bob is Robert Hsiung, MD,
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Posted by Phillipa on November 18, 2004, at 16:46:13
In reply to Re: How do I know IF I am a slow metabolizer? » stresser, posted by Larry Hoover on November 18, 2004, at 15:00:48
Lar, You are so knowledgeable that I am curious about your occupation. Phillipa
Posted by Larry Hoover on November 18, 2004, at 18:48:04
In reply to Re: How do I know IF I am a slow metabolizer?, posted by Phillipa on November 18, 2004, at 16:46:13
> Lar, You are so knowledgeable that I am curious about your occupation. Phillipa
I trained as an environmental toxicologist. I was working for an international environmental advocacy group when I became ill. I haven't done that kind of work in a while, so I'm not too comfortable calling myself that any more. I am a contract geek, I guess. A brain for hire.
Lar
Posted by stresser on November 18, 2004, at 20:21:18
In reply to Re: How do I know IF I am a slow metabolizer? » Phillipa, posted by Larry Hoover on November 18, 2004, at 18:48:04
Geek my ***, you intimidate the heck out of me! I am trying to make something out of the information you gave me, but it will take some time. I do mean T I M E.... WOW. You say you became ill? Do you mine my asking what happened? -L
Posted by Phillipa on November 18, 2004, at 22:15:04
In reply to Re: How do I know IF I am a slow metabolizer?, posted by stresser on November 18, 2004, at 20:21:18
Stresser, He doesn't intimidate me, I respect him for his knowledge and would commend Lar for being so informed. I would like to see it in layman's terms though because I am not good at chemistry.Phillipa
Posted by Larry Hoover on November 18, 2004, at 22:24:41
In reply to Re: How do I know IF I am a slow metabolizer?, posted by stresser on November 18, 2004, at 20:21:18
> Geek my ***, you intimidate the heck out of me! I am trying to make something out of the information you gave me, but it will take some time. I do mean T I M E.... WOW. You say you became ill? Do you mine my asking what happened? -L
I am sorry if I intimidate. It certainly isn't an intent of mine to do so. If there's any question you want to ask, any question at all, please do. I'd be happy to try and answer so that you comprehend what I'm trying to communicate. Sometimes I forget everybody didn't love chemistry class.
I had what is colloquially known as a nervous breakdown. I pretty much lost everything that mattered to me in a few short months. I'm a real life Humpty Dumpty, I guess.
Lar
Posted by Phillipa on November 18, 2004, at 22:43:11
In reply to Re: How do I know IF I am a slow metabolizer? » ZenTen, posted by Larry Hoover on November 17, 2004, at 22:31:00
Can you explain why someone can take a med for a while stop taking it, then be put back on it and then it doesn't work anymore,or does the opposite of what it did before. for example took paxil and felt like a million dollars along with small doses of xanax (also drank beer) first time and not the second time when it no longer worked? Have not had a drink in 7 years and have felt progressively worse over time. Phillipa P.S. Don't say start drinking because am on chloral hydrate for sleep.
Posted by Larry Hoover on November 18, 2004, at 22:43:58
In reply to Re: How do I know IF I am a slow metabolizer?, posted by Phillipa on November 18, 2004, at 22:15:04
> Stresser, He doesn't intimidate me, I respect him for his knowledge and would commend Lar for being so informed. I would like to see it in layman's terms though because I am not good at chemistry.Phillipa
OK. Hmmm.
Your liver is your toxic waste incinerator. In so many words, it oxidizes, transforms and labels waste for disposal via feces or urine.
We know enough to say that certain chemical structures are more likely to be transformed in one type of liver reaction than another. The chemical reactions themselves are helped along by enzymes, special purpose "factories" with one specific task. One kind might snap a piece off of this molecule, and another might tack on an extra bit onto that other one, but the whole point is to accomplish two main things. One, to make toxins less toxic. Your liver sees the drugs we take as toxins, and it wants them nullified. Two, it labels them for excretion. Many molecules get "flagged" with special molecular tags, so the kidney knows to let them go on out with the rest of the waste in urine.
There are a whole lot of different chemicals that the body sees as toxic, so there are a whole lot of different enzymes to take care of things. Some are general purpose enzymes, the workhorse enzymes. Mess with those, and a lot of nasty stuff stays nasty instead of being detoxified. Examples of those workhorses are 2D6, 3A4, 2C19, and 1A2. Many drug treatment schemes require those enzymes to be working properly, or the drugs will build up to toxic levels, or their metabolites will instead.
Drug interactions are caused, really, by liver stress. If you ask the liver to do too much at the same time, it doesn't do the work efficiently. Adding in a new drug can make an old drug toxic, one that didn't cause toxic problems before. That's a drug interaction. Taking tylenol while you have alcohol in your blood causes a severe interaction in the liver, so severe it can cause liver cells to die. Interactions aren't always obvious.
Nowadays, drug metabolism is determined for every new drug that comes to market. You can usually find out how it is metabolized by reading the drug monograph. Hopefully, we can learn what sorts of drugs are probably okay for one individual to take, and others not okay, based on the individual's liver capacity. We're on the verge of being able to do that.
Ask me questions, if you wanna.
Lar
Posted by Phillipa on November 18, 2004, at 23:52:12
In reply to Re: How do I know IF I am a slow metabolizer? » Phillipa, posted by Larry Hoover on November 18, 2004, at 22:43:58
Now your're talking my language. Thank-you. Let me sleep on some further questions and get back to you tomorrow. pleasant dreams!phillipa
Posted by jasmineneroli on November 19, 2004, at 1:55:14
In reply to Re: How do I know IF I am a slow metabolizer?, posted by Phillipa on November 18, 2004, at 23:52:12
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?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?).
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???
Ibuprofen has little analgesic effect for me, so does that indicate poor metabolism of 2C9?
Acetaminophen has little effect too, except in high doses(1A2, 2E1 & 3A4 again). Since caffeine does work quickly (1A2 & 3A4) should I assume that the 2E1 in acetaminophen is not being metabolized properly???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??
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!and Larry, I really do think you should write a book. You have an excellent writing style - varied vocab. etc.etc. :)
Take care
Jas
Posted by gromit on November 19, 2004, at 1:59:33
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
Maybe this explains why codeine does nothing for me, but vicodin is a stimulant. So much to learn, so little remaining brain cells.
Rick
Posted by andromeda on November 19, 2004, at 9:25:43
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
Ok, lets just assume one is a slow metabolizer. I just started on Nardil (which may be slowing my metabolizing even more). Nardil has been prescribed at 15 mg week one, 30 mg week two and 45 mg week three because I have trouble tolerating medicine. I am starting week two. Side effects are increasing but so far bearable for me but maybe not for others in my family. Depression and social phobia has not really lifted yet and also becoming quite cranky. First 4 days were better than the last 3 days. So what I am wondering is if it would be better to go in the opposite direction. Would it be better to decrease dose instead of increase dose? Take 15 mg every 3 days or just take maybe quarter of a tablet per day? I am also on 50mg of Lamictal bc increasing the dose does not seem to help but no Lamictal causes me more weepiness and sensitivity to rejection.
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
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