Posted by Larry Hoover on March 4, 2005, at 10:21:40
In reply to Re: Drug interactions q. » Larry Hoover, posted by banga on March 2, 2005, at 15:35:37
> Thank you Larry for laying it out so clearly!
You're very welcome.
> I recently added 100 mg of Luvox to :
> 75 mg desipramine
> 5mg Abilify
> 30mg Adderall
>
> And within a day noticed orthostatic hypotension--knew the Luvox may be upping the desipramine; BUT also the next day felt very spacey and my tongue felt odd--sensations that I had had when I had once tried a higher Abilify dosage. So I suspected there must be an interaction RE Luvox and Abilify too. Thanks for the confirmation.
>
> SO I am now going to try 2.5mg Abilify and 75mg desipramine and only 50mg Luvox--all three then will have lengthened half-lives. Figures the three drugs that seem logical for me should interact...
> I wasnt sure if I can assume the Luvox itself will be raised in my system too...50mg is a pretty small dose, didn't know if I could even hope for benefit.
>
> Good news is that other than spaciness the combo seems to be doing good things!Now that you're feeling comfortable, I'm going to raise another factor that I purposely did not discuss before. One bit at a time.....
One of the other possible issues with respect to interactions at liver enzymes involves active metabolites. The way I described things up until now, I was only speaking in terms of the parent drug, which was assumed to be responsible for all effects. That is often not the case.
When a monotherapy comes to equilibrium in the body (generally after the passage of five half-life periods at a set dose), there is a balance of active parent to metabolite concentrations. If one (or more) of those metabolites exerts its own effects, then the ratio of active parent:active metabolite concentrations is part of the total drug effect.
Whenever a new substance/drug is introduced to a monotherapy system, and that substance affects enzyme activity, then the ratios of parent:metabolite are shifted as well. That can change the "balance" of effects, often increasing side-effects from the parent drug, or inhibiting beneficial effects of active metabolites (that would be the result of competition, or enzyme inhibition). Those relative effects are inverted if an enzyme is *induced* (up-regulated) by the new substance.
I just throw these ideas in for a more complete understanding of what may happen with combinations of drugs. In the end, it's only fair to say that an individual will likely have to experiment with doseages, to find the most comfortable new balance point.
Lar
poster:Larry Hoover
thread:465379
URL: http://www.dr-bob.org/babble/20050304/msgs/466418.html