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
poster:Larry Hoover
thread:417092
URL: http://www.dr-bob.org/babble/20041118/msgs/417534.html