Posted by Adam on August 9, 2001, at 20:43:37
In reply to Babble Brainiacs, please read (Elzbth, I humbly..., posted by Adam on August 8, 2001, at 21:24:22
Medlib (and any others who wish to discuss),
Hi. I really don't know what's at the clinician's disposal as far as testing for plasma levels of various drugs. From what you are telling me (you seem quite informed on these issues), doing what I would have liked to (as described in my post below) would perhaps be impossible, or at best prohibitively expensive. However, I think it should be fairly straightforward to get a urine test for methamphetamine, right? I mean, if the Army recruiter can do it, why couldn't my doctor? Say, as I'm tapering, I wait at, say, 10mg b.i.d. until I'm assured a steady-state level of l-meth. Then, after I wash out, and begin titrating back up, with grapefruit juice, of course (I would hope to get to that dose at least, the same as I was taking/day on the patch), I could wait an appropriate amount of time, and check on l-meth levels again. If they are radically different, then I could take that as pretty good evidence my hypothesis is correct, no?
I know, in the end, that my perception of benefit is all that _really_ matters, but I'd like to have more information, or some indicator that the idea "really works". I might hope to follow up maybe six months later with another urine test, and if things are the same, I would be somewhat assured the strategy has long-term benefit.
Of course, I would have to be careful about other medications I took. Since I rarely take any medicine at all, that shouldn't be too tough. Hopefully before I'm old and grey, and taking 16 different medications, the patch will be available for depression.
> OK, so I'm reaching a little here. Bear with me...
>
> I've been doing a fair amount of reading and reviewing in an attempt to get to the bottom of some weird physical symptoms that I've had. In the mean time, I've been experiencing some new issues, specifically my b.p. has been spiking, almost like clockwork, for the past few days. I just took it: Approx 160/95. This is quite high for me. Not only did I not eat any questionable foods today, I haven't eaten anything since 11:00 AM this morning, and that was an apple. For breakfast I had a bowl of Rice Chex and a bagel.
>
> To deal with some dreadful sleep problemss, I've been self-medicating with diphenhydramine. I've taken one every night for around ten days or so. I think this may, at least in part, have something to do with this apparently spontaneous hypertension I've been experiencing lately. Benedryl, according to some reports, inhibits CYP2D6. 2D6 metabolizes l-methamphetamine. l-methamphetamine ups NE. More l-meth, more NE, and, on an MAOI, that means hypertension.
>
> So that's the theory, in a nutshell. Nuts?
>
> Well, I'm going to dump diphenhydramine right now and switch, after a few days of b.p. monitoring, to neurontin. Let's see how it goes.
>
> But all this wondering about selegiline metabolism, esp. first-pass metabolism, has brought me to another nutty idea. Here it is:
>
> Transdermal selegiline works as an antidepressant even at the low dose of 20mg/day. The reason for this is that avoidance of first-pass metabolism increases the bioavailablity of the parent compound, which, in turn, decreases the levels of metabolites from what is found using oral delivery. This also means robust non-specific MAO inhibition at a lower dose than one can achieve by oral delivery, obviously.
>
> First-pass metabolism of selegiline is significant in the gut. Specifically, intestinal epithelium has losts of CYP3A4 in it. This is the enzyme that is largely responsible for the conversion of l-selegiline into l-methamphetamine. This conversion also occurs in the liver (same enzyme, diff. place), but the major locus is the gut.
>
> So, avoid CYP3A4 in the gut, and you get more selegiline and less pesky l-amphetimine, which is, in all likelyhood, not my friend for a variety of reasons. What if you inhibit CYP3A4 in the gut?
>
> There are two pretty easy ways to do this: Take some ketoconazole (anti-fungal), or pound grapefruit juice (bergamottin, and perhaps others). It turns out grapfruit juice has this other nifty property: It inhibits the action of P-glycoprotein, which is responsible for, among other things, drug resistance in cancers. P-glycoprotein does its job by booting drugs out of a cell as quickly as they come in, preventing them from working. I guess the P-glycoprotein inhibitors are likely to be furancoumarin derivatives, and maybe some others. Anyway, grapefruit juice might have two means of increasing bioavailability: It inhibits metabolism, and drug exclusion, at the same time.
>
> SO, why not measure how much l-deprenyl and l-methamphetamine are in my blood at the 30mg/day dose. This can be done easily enough with the right tools, though I don't know how I would go about getting such data outside of a research setting. Say I could: I then taper off selegiline until the blood levels of l-dep. and l-meth. are significantly/completely reduced. Then I start again taking selegiline, maybe at 5mg/day b.i.d., but I wash eash dose down with a great big glass of grapefruit juice. After a few days of this, I get the plasma levels taken again. I titrate until I reach or exceed the blood level of l-dep. I have now. Theoretically, the l-meth. levels should be significantly lower than they are now.
>
> OK, is this just totally stupid and completely impractical? Are they going to put me in restraints just for having the temerity to seriously suggest such an idea? Is it even remotely possible that a physician this side of Neptune would go along with such a goofy plan? I figure if I'm tapering off of selegiline anyway, to rule out or in the possiblilty that my symptoms are due to a pheochromocytoma, why not get back on it with a twist, so to speak?
>
> Be honest, I can take it. I'm always willing to try something different, if it makes sense. I'm not always sure what makes sense, though.
>
> Thanks, in advance.
poster:Adam
thread:74266
URL: http://www.dr-bob.org/babble/20010809/msgs/74383.html