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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by LynneDa on July 14, 2008, at 9:21:23
Quick Question: Drugs, in general, seem to stay in my system longer than they're supposed to. For example, one Benadryl makes me sleepy for a good 12 hours! .125 Halcion is supposed to get out of your system quickly, but I took it last night at 11pm. It is now 9am and I can still feel the effects. I also take 20mg Lexapro at night and 300 mg of Wellbutrin, split between 2 pills per day.
I know there are a lot of people out there in Babble-land with expertise and knowledge about pharmacology. Does anyone know why that is and if I can do something to change it?
Thanks for any thoughts you can share!
~ Lynne
Posted by Phillipa on July 14, 2008, at 10:54:42
In reply to Drug Metabolism Question, posted by LynneDa on July 14, 2008, at 9:21:23
I think we're all just different. Phillipa
Posted by Larry Hoover on July 14, 2008, at 14:02:52
In reply to Drug Metabolism Question, posted by LynneDa on July 14, 2008, at 9:21:23
> Quick Question: Drugs, in general, seem to stay in my system longer than they're supposed to. For example, one Benadryl makes me sleepy for a good 12 hours!
Diphenhydramine depends on enzyme 2D6, and to a lesser extent enzyme 3A4.
> .125 Halcion is supposed to get out of your system quickly, but I took it last night at 11pm.
Largely uses 3A4.
> It is now 9am and I can still feel the effects. I also take 20mg Lexapro at night
Escitalopram uses 3A4 and 2C19.
> and 300 mg of Wellbutrin, split between 2 pills per day.
Bupropion uses 2D6, and others.
> I know there are a lot of people out there in Babble-land with expertise and knowledge about pharmacology. Does anyone know why that is and if I can do something to change it?
Maybe 10% of the population has a defective 2D6 enzyme system.....either very weak, or even non-existent, activity. Any drug that depends on that enzyme for metabolism will have an extended, and often enhanced, effect. Moreover, the magnitude of the effect increases with repeated doses, as blood concentrations can rise substantially above normal levels due to low clearance rates.
Enzyme 3A4 is the most heavily used liver detox enzyme, and it can respond to demand by being upregulated (i.e. more of it is produced), although you can't count on that happening. However, drugs which use it must compete for whatever is present, and once again, enhanced effects can result.
In your case, based on pure supposition, I'd suspect that you have low 2D6 activity, and some moderate to heavy interaction at 3A4. Do not consume 3A4 inhibitors (e.g. grapefruit and/or its juice). You might also try lower doses of the drugs that are causing you problems. The lower dose might actually give you "normal" blood concentrations.
Lar
Posted by LynneDa on July 14, 2008, at 18:16:31
In reply to Re: Drug Metabolism Question » LynneDa, posted by Larry Hoover on July 14, 2008, at 14:02:52
Thanks Larry, I knew I could count on you for an explanation :-). You've given me something to think about and research further.
~ Lynne
Posted by LynneDa on July 14, 2008, at 18:20:22
In reply to Re: Drug Metabolism Question » LynneDa, posted by Phillipa on July 14, 2008, at 10:54:42
I know, Phillipa, you're right! But, I'm always searching to understand what is going on inside of me in the hopes I'll find something to straighten out my brain chemistry :-)
~ Lynne> I think we're all just different. Phillipa
Posted by Crotale on July 20, 2008, at 22:52:20
In reply to Re: Drug Metabolism Question » Larry Hoover, posted by LynneDa on July 14, 2008, at 18:16:31
You can get tested for enzyme deficiency. If you are deficient in CYP2D6, in particular, you want to be very careful with tricyclics. I had a great response to desipramine - but then I had a partial seizure and it turned out my serum level was elevated.
What meds are you on right now? A number of drugs inhibit these enzymes. For example, Prozac and Paxil inhibit 2D6, while Luvox and Xanax inhibit 3A4. (These are only a couple examples.)
-Crotale
Posted by LynneDa on July 21, 2008, at 19:16:47
In reply to Re: Drug Metabolism Question » LynneDa, posted by Crotale on July 20, 2008, at 22:52:20
Hi & thanks for your response!
I am on 20mg Lexapro at night, 150 mg Wellbutrin in morning - I'm supposed to go up to 300mg, 1/2 in morning, 1/2 in afternoon, but it makes me a little edgy! I'm foggy all day - can't remember things, can't keep track of what I'm doing (I'm 44 - never had this issue til I went on meds 5 years ago). I have trouble sleeping so sometimes I'll take halcion (sp?) or just Benadryl - big hangover the next day!I'm seeing a new internal med doc in a few weeks and I'm going to switch p-docs cuz mine is not really helping me - just keeps writing me scrips. I'd like to ask the internal med doc to run tests - thyroid, etc., so I will ask him about enzyme tests too. Anything else you can think of, I'll throw that in too :-).
Thanks again!
~ Lynne
************************************You can get tested for enzyme deficiency. If you are deficient in CYP2D6, in particular, you want to be very careful with tricyclics. I had a great response to desipramine - but then I had a partial seizure and it turned out my serum level was elevated.
>
> What meds are you on right now? A number of drugs inhibit these enzymes. For example, Prozac and Paxil inhibit 2D6, while Luvox and Xanax inhibit 3A4. (These are only a couple examples.)
>
> -Crotale
Posted by maree on July 22, 2008, at 0:34:25
In reply to Re: Drug Metabolism Question » Crotale, posted by LynneDa on July 21, 2008, at 19:16:47
So can you increase your level of CYP2D6?
I do not react to any anti depressant, actually I do not get any real benefit from anything that I put in my mouth (including food), except pain killers, and that is only for a short time.
Posted by Larry Hoover on July 22, 2008, at 8:21:34
In reply to Re:, posted by maree on July 22, 2008, at 0:34:25
> So can you increase your level of CYP2D6?
No, this enzyme is not inducible. What your genes gave you is all you have, and that amount can be effectively reduced by any inhibitors or substrates.
> I do not react to any anti depressant, actually I do not get any real benefit from anything that I put in my mouth (including food), except pain killers, and that is only for a short time.
Rather than having low enzyme levels, you may have what are called super-metabolizing enzymes. These enzymes process chemicals at many times the "normal" rate. I put the word in quotation marks because super-metabolizers are normal. They just differ from the population mean (called the norm). It might be worth having enzyme function testing performed, if the expense is not an obstacle.
Lar
Posted by Crotale on July 25, 2008, at 23:04:39
In reply to Re: 2D6 » maree, posted by Larry Hoover on July 22, 2008, at 8:21:34
I agree with Larry about this -- I don't think your problem is due to enzyme inhibition or induction from any of the meds you're on. This is definitely something you should tslk to s doc about, and emphasize how serious it is.
-Crotale
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