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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Lightshifter on March 24, 2004, at 20:37:33
I emailed this to Dr. Bob but I guess he can no longer get to reply to these directly. If anyone has any credible information on what happens when 2 drugs are given at the same time when they are both metabolized by the same enzyme (2d6) I'd appreciate a response... (Strattera and Nortryptaline are the 2 drugs being used at same time.)
Dear Dr. Bob,
I've been trying to get an answer to a question regarding the metabolizing of multiple drugs by the CYP450-2D6 enzyme.
Can you tell me if drug metabolism is decreased when multiple drugs are used that are metabolized by the same enzyme (2D6)? I have a friend who has been prescribed multiple drugs which are metabolized by it and was wondering if that may be reducing the metabolization and therefore the effectiveness of the drugs due to them competing for the same metabolizer.
I'd appreciate any help you might be able to provide and if you know of any links where this may be discussed I'd love to review the information.
Thanks For Your Help,
Dan Hunt
Posted by zeugma on March 24, 2004, at 20:58:59
In reply to Concurrent use of 2 Drugs Metabolized by 2d6 Enzym, posted by Lightshifter on March 24, 2004, at 20:37:33
Hello,
I take Strattera and nortriptyline concurrently and have not noticed any loss of efficacy due to the combination. On the Strattera PI sheet it says that no dosage adjustment is necessary for drugs metabolized by the CYP-2D6 pathway. Has your friend noticed any problems arising from the combination?
Posted by King Vultan on March 25, 2004, at 7:52:14
In reply to Concurrent use of 2 Drugs Metabolized by 2d6 Enzym, posted by Lightshifter on March 24, 2004, at 20:37:33
> I emailed this to Dr. Bob but I guess he can no longer get to reply to these directly. If anyone has any credible information on what happens when 2 drugs are given at the same time when they are both metabolized by the same enzyme (2d6) I'd appreciate a response... (Strattera and Nortryptaline are the 2 drugs being used at same time.)
>
> Dear Dr. Bob,
>
> I've been trying to get an answer to a question regarding the metabolizing of multiple drugs by the CYP450-2D6 enzyme.
>
> Can you tell me if drug metabolism is decreased when multiple drugs are used that are metabolized by the same enzyme (2D6)? I have a friend who has been prescribed multiple drugs which are metabolized by it and was wondering if that may be reducing the metabolization and therefore the effectiveness of the drugs due to them competing for the same metabolizer.
>
> I'd appreciate any help you might be able to provide and if you know of any links where this may be discussed I'd love to review the information.
>
> Thanks For Your Help,
>
> Dan Hunt
>
>No, the problem generally winds up being just the opposite in this type of situation, as it is common for the older antidepressants to inhibit the 2D6 enzyme. When this happens, the enzyme becomes tied up with one drug and is unable to properly metabolize the other. However, rather than reduce the effectiveness of the other drug, the strength winds up being magnified, as the drug stays in the bloodstream longer than normal, has a higher peak plasma level, and a higher sustained blood plasma level.
It may help to clarify what's going on by pointing out that in most cases, the metabolism in the liver is not necessary for these drugs to function. Rather, metabolism by mechanisms such as the CYP-450 enzyme system is what allows the body to get rid of the drugs, usually by hydroxylating them to increase their water solubility and allowing the kidneys to excrete them. A drug such as nortriptyline does not need to be metabolized into another form to be effective, but once it is acted on by the CYP-450 enzyme system, being metabolized to 10-hydroxy-nortriptyline, for instance, it is removed from the body in fairly short order.
That be said, you are correct that both Strattera and nortriptyline are 2D6 substrates, but only nortriptyline is a 2D6 inhibitor. The secondary amine tricyclics are only weak to moderate inhibitors, however, so I would not expect this to be a giant problem, the Strattera blood plasma levels probably going up moderately. More serious are problems involving the reverse, where a tricyclic is combined with a strong 2D6 inhibitor such as Prozac or Paxil. In those cases, levels of the tricyclic can rise to dangerous levels, as these drugs are cardiotoxic and lethal in overdose.
Todd
Posted by Ame Sans Vie on March 25, 2004, at 9:03:24
In reply to Re: Concurrent use of 2 Drugs Metabolized by 2d6 Enzym » Lightshifter, posted by King Vultan on March 25, 2004, at 7:52:14
What King Vultan said is right on. I just also wanted to point out the fact that 2D6 is unique in that it is *uninducible*. No known drugs or foods speed up its processes -- certainly not the case for 1A2, 2C19, 3A4, and the rest.
Also, about inhibitors of 2D6 causing reduced efficacy of some drugs, this *does* happen in a few cases. Codeine, hydrocodone, oxycodone, and tramadol, for example, will not be (as) effective when administered with a 2D6-inhibitor. They all rely on this enzyme to convert to their prodrug forms -- morphine, hydromorphone, oxymorphone, and o-desmethyltramadol respectively.
Posted by Sad Panda on March 25, 2004, at 10:04:17
In reply to Re: Concurrent use of 2 Drugs Metabolized by 2d6 Enzym, posted by Ame Sans Vie on March 25, 2004, at 9:03:24
> Also, about inhibitors of 2D6 causing reduced efficacy of some drugs, this *does* happen in a few cases. Codeine, hydrocodone, oxycodone, and tramadol, for example, will not be (as) effective when administered with a 2D6-inhibitor. They all rely on this enzyme to convert to their prodrug forms -- morphine, hydromorphone, oxymorphone, and o-desmethyltramadol respectively.
>
>Wouldn't this just mean that the onset of effects is slower from these drugs?
Cheers,
Panda.
Posted by KimberlyDi on March 25, 2004, at 11:36:09
In reply to Re: Concurrent use of 2 Drugs Metabolized by 2d6 Enzym » Lightshifter, posted by King Vultan on March 25, 2004, at 7:52:14
Along these lines of thought... increasing or decreasing effectiveness... I went to the emergency clinic for a deep cut on my foot over the weekend. Without asking what medications I was currently taking, they prescribed me Darvocet-N 100mg for the pain. I am on generic Tegretol 200mg x 2, Imipramine 100mg x 1, and Trazadone 100mg x 1. I don't know if I can believe everything that I read on the internet, but is this combination really that bad? I've cut out my meds until my foot is better but I'm feeling the loss of my meds and would rather take them.
Thanks, Kim
Posted by Sad Panda on March 25, 2004, at 13:10:13
In reply to Concurrent use of Darvocet-N with Tegretol, etc., posted by KimberlyDi on March 25, 2004, at 11:36:09
> Along these lines of thought... increasing or decreasing effectiveness... I went to the emergency clinic for a deep cut on my foot over the weekend. Without asking what medications I was currently taking, they prescribed me Darvocet-N 100mg for the pain. I am on generic Tegretol 200mg x 2, Imipramine 100mg x 1, and Trazadone 100mg x 1. I don't know if I can believe everything that I read on the internet, but is this combination really that bad? I've cut out my meds until my foot is better but I'm feeling the loss of my meds and would rather take them.
>
> Thanks, Kim
>Darvocet contains Propoxyphene. Imipramine + Propoxyphene = the possibility of serotonin syndrome. Can you get your doc to give you something that isn't a serotonin reuptake inhibitor? Oxycodone would be good, Percocet or Percodan.
Cheers,
Panda.
Posted by jane d on March 26, 2004, at 12:35:59
In reply to Concurrent use of 2 Drugs Metabolized by 2d6 Enzym, posted by Lightshifter on March 24, 2004, at 20:37:33
http://medicine.iupui.edu/flockhart/
for a list of interactions and footnotes. This site will also create pub med queries on specific drugs. The site has added a lot since I last looked at it.http://www.acnp.org/G4/GN401000086/Default.htm This has an explanation of how it works.
I'm not sure that it's possible to get anyone to say that drug 1 is actually interacting to a significant degree with drug 2 in a specific person since there will always be other substances involved and since people differ in the amount of these enzymes they start with. Certainly many of the predicted interactions don't always occur. I've taken prozac and codeine for instance (with fingers crossed I'll admit) and had no problem.
Jane
This is the end of the thread.
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