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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 48. This is the beginning of the thread.
Posted by ZenTen on November 17, 2004, at 12:17:12
Like many people here I am pretty refractory to most meds I have tried and have pretty wicked side-effects to most of them with few exceptions.
Nortriptyline seems to help my depression just a bit--which I still really appreciate since most other meds don't do too much at all, and even make me more depressed!
However, I can only seem to tolerate doses up to 25mgs. Anything even a little over that (say 40mgs) makes me have severe side -effects. Like heart pain, slow and fast pulse and bad sedation.
Doses at 25mgs have almost no side-effects at all though? I plan to continue ont this amount.How can I tell if I am a slow metabolizer? Maybe I have therapuetic doses with only 25mgs? I know they can pull a blood-level but can they test in general,to see if you are a slow metabolizer?
Posted by Larry Hoover on November 17, 2004, at 22:31:00
In reply to How do I know IF I am a slow metabolizer?, posted by ZenTen on November 17, 2004, at 12:17:12
> Like many people here I am pretty refractory to most meds I have tried and have pretty wicked side-effects to most of them with few exceptions.
>
> Nortriptyline seems to help my depression just a bit--which I still really appreciate since most other meds don't do too much at all, and even make me more depressed!
>
> However, I can only seem to tolerate doses up to 25mgs. Anything even a little over that (say 40mgs) makes me have severe side -effects. Like heart pain, slow and fast pulse and bad sedation.
> Doses at 25mgs have almost no side-effects at all though? I plan to continue ont this amount.
>
> How can I tell if I am a slow metabolizer? Maybe I have therapuetic doses with only 25mgs? I know they can pull a blood-level but can they test in general,to see if you are a slow metabolizer?I am not advocating this process, as I do not know just how accurate it is, but there are companies which claim to assess your enzyme activity levels. An example is http://www.healthanddna.com/drugreactiontest.html
The drug reaction panel is $600.There is also a "laboratory in a chip" marketed by Roche that does virtually instant testing of two enzymes: http://www.roche-diagnostics.com/products_services/amplichip_cyp450.html
It is approved in Europe, but only used for research purposes in the USA.One fairly common manifestation of poor metabolism is at the 2D6 enzyme. If you're a poor metabolizer there, you will get little pain relief from codeine, for example, but you'll get all the side effects. If you're a fast metabolizer, codeine makes you quite high. Sometimes you can get clues about your metabolism from the drugs that have failed you. You can look up the enzymes that work with different drugs at this site: http://www.edhayes.com/startp450.html
You might be able to figure it out for yourself.Lar
Posted by reefer on November 18, 2004, at 7:32:33
In reply to How do I know IF I am a slow metabolizer?, posted by ZenTen on November 17, 2004, at 12:17:12
My doctor just sent me the hospital lab and they drew a blood sample from which they could do genotyping and they concluded i was a poor CYP 2D6 metabolizer and that i was a normal metabolizer of CYP 3A4.
Posted by reefer on November 18, 2004, at 7:35:20
In reply to Re: How do I know IF I am a slow metabolizer?, posted by reefer on November 18, 2004, at 7:32:33
He didn't send the lab to me, he sent me to the lab! Sorry!
Posted by stresser on November 18, 2004, at 12:12:38
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
Lar- I went to the website you suggested in the previous post, and of course, I don't understand a single thing about it. I looked up Burpropion and Topomax (topiromate?)and there were letters with number beside them. What does all that mean? Can you tell me what those two drugs do to the body....speed up the metabolism or slow down? Or..does the table just indicate how fast the drug is metabolized in the body? I hope I don't sound like the blond that I'm really not!-L
Posted by Larry Hoover on November 18, 2004, at 15:00:48
In reply to Re: How do I know IF I am a slow metabolizer? » Larry Hoover, posted by stresser on November 18, 2004, at 12:12:38
> Lar- I went to the website you suggested in the previous post, and of course, I don't understand a single thing about it. I looked up Burpropion and Topomax (topiromate?)and there were letters with number beside them. What does all that mean? Can you tell me what those two drugs do to the body....speed up the metabolism or slow down? Or..does the table just indicate how fast the drug is metabolized in the body? I hope I don't sound like the blond that I'm really not!-L
I shoulda given more information, eh?
The cytochrome liver enzymes, sometimes called the P450 enzymes, change chemicals that are circulating in the blood to make them more readily excreted in bile or in urine. Some of those chemicals are naturally present, and some are ingested. The liver uses the P450 enzymes to detoxify the blood.
There are dozens, if not hundreds, of different P450 enzymes. To organize them, they are classified into families (by number), then subfamilies (by letter), then again into gene variants (again, by number). So, enzyme Cytochrome P450 family 2 subfamily D gene 6 enzyme is called by its shorter name, CYP2D6, or just 2D6.
Two of the most active and effective detoxifying enzymes are 2D6 and 3A4. These are the ones most often needed to detoxify pharmaceutical drugs, for example. So, anything that messes with the functioning of these two enzymes can spell trouble.
Now, some terminology. A substrate is a chemical which is acted on by a particular enzyme. An example of a substrate for 2D6 is codeine. It is converted by this enzyme to morphine.
An inhibitor slows down the rate at which an enzyme does its work. A 2D6 inhibitor would reduce the analgesic effect of codeine, for example. Grapefruit juice inhibits enzyme 3A4, as another example.
An inducer does just the opposite. It speeds the enzyme up. An inducer of 2D6 would increase the analgesic effects of codeine, and perhaps cause mood alteration. St. John's wort induces 3A4, as an example of this effect.
Both inhibition and induction are examples of interactions. We say two drugs interact when one affects the enzyme transformation of the other, or in some situations, they can even affect each other simultaneously.
So, to thoroughly understand all those letters and numbers, you need to look at more than one table. You need to note (on paper is best) what enzymes are required to metabolize any drugs you are taking (Table 1), i.e. of which enzymes is the drug a substrate. There can be more than one enzyme.
Then, go to Table 2 and see if any drugs you are taking induce or inhibit any enzymes. This will tell you about possible interactions.
With those two lists of enzymes, you want to compare and see if you're taking a drug that inhibits or induces an enzyme that the other drug needs. Also, just taking two drugs that need the same enzyme can produce an interaction, because the enzyme can only do so much work in a given period of time.
I hope this article isn't too complicated.
http://www.aafp.org/afp/980101ap/cupp.html
Then, finally, you come up with the genetic factors. Some people have very poor 2D6 activity because they were born with an ineffective gene combination. For these "poor metabolizers", it can be as if there's a drug interaction even though they're only taking a single medication. Their 2D6 enzyme can't handle the detoxification burden, and they get bad side effects because their body can't handle the drug at all.
Just so you get some idea, I've seen references that show that 2D6 activity can vary by a multiple of about 115 times (or maybe even more than that). That means that some people's 2D6 enzyme has less than 1% of the capacity of the some other people's. There's a similar genetic variability in 2C19, 2C9, and 1A2. And we surely don't know of them all.
If you need more explanations, feel free to ask.
Lar
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
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