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
poster:Larry Hoover
thread:417092
URL: http://www.dr-bob.org/babble/20041118/msgs/418570.html