Posted by Adam on August 9, 2001, at 11:24:16
In reply to Re: I may need help...., posted by michael on August 8, 2001, at 20:56:09
Hi, Michael,
Thanks for your kind words. For sleep, I'm going to try neurontin, but first I want to do a little experiment...I'm going to let myself clear of diphenhydramine and wait to see if my b.p. keeps doing the weird things it has been doing. If so, then the pheochromocytoma theory maybe looks more credible than my metabolism theory (both could be completely wrong). I have a feeling that neurontin could lower b.p. (GABAnergic drugs may do that), so I don't want to add another complicating variable until I've checked everything out.
As for the patch, I sure hope it gets approved sooner than later. I've kind of given up on waiting for it, though. As time passed, and I gain more experience with such issues (to some extent through my job), the behavior of the FDA becomes more and more mysterious and questionable. I no longer feel I can predict what they will decide, or how long it should take for them to reach a decision.
> Adam -
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> Sadly, not much to contribute on this one.... (with the possible exception of the thought of finding diphenhydramine tablets, or even capsules, that you could split into less than 25mg doses - I unfortunately need at least 50mg to hope for some help with sleep...)
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> I don't have as much time to spend "here" these days, but when I check in, I make a point of checking out your posts - because I appreciate so much what you've had to contribute in the past.
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> Just off the top of my head - which ain't much - maybe trying something besides diphendydramine for regulating your sleep cycles... if not low doses of clonazepam or lorazepam, perhaps exploring melatonin?
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> Don't know if that's a good idea or not...
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> In any case, hang in there - fwiw, you've been a source of hope, for me at least, with your accounts of your experiences with selegiline, both the patch & orally.
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> With any luck, you'll get through this some way (sorry I don't have more to offer on this one), and be able to try the patch again - with which you had such good results - in the next 9 to 12 months.
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> Fwiw, I'm going to keep trying whatever my pdoc will allow me to (seems quite (too) conservative), and hope I find something that works... but in the back of my mind, I have to admit that I'm looking forward to trying the patch, once it's "FDA Approved." It just sounds like you had such positive results, and "symptoms" similar to mine, that I'm hopefull...
>
> Anyway, sorry for rambling so long... count yourself luck that at least you have one doc that takes you seriously, and evaluates your ideas objectively. In my admittedly limited experience, I find that to be a luxury. If you don't blindly try SSRI after SSRI, you may just be perceived as "difficult."
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> Fwiw, if your pdoc becomes confrontational/difficult, at least you have your PCP to fall back on, and you can work from there...?
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> Once again, sorry for the ramble - good luck, & I too am keeping my fingers crossed for the patch...
>
> michael
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> > Hi, midlib,
> >
> > Yes, pheochromocytoma is the type of tumor my doctor was referring to. I have been reading of certain pseudopheochromocytomas, which, not suprisingly, are usually caused by some or other drug or interaction of drugs...
> >
> > So here's a little theory: My sleep drug of choice, diphenhydramine, inhibits cytochrome P4502D6. I've been convinced for quite a while that I may be deficient in that enzyme as it is, since I have such low tolerance for certain drugs. Maybe it's worth noting that a relatively small dose of diphenhydramine knocks me right on my butt as it is (25mg and I'm near-comatose...nice until the next morning when I can't see straight).
> >
> > Anyway, CYP2D6 is supposedly not important in the metabolism of selegiline, desmethylselegiline, or l-amphetamine, the latter couple being two of the three major metabilites of selegiline. However, in Clin Pharmacol Ther 1998 Oct.; 64(4):402-411, they mention that those with the 2D6 polymorphism (deficient in 2D6) had around half-again as much l-methampetamine floating around as normals (this result was quite statistically significant, though the n was small).
> >
> > l-methamphetamine doesn't do much to dopamine, but its ability to increase NE efflux is only 2-3x less than that of d-methamphetamine. If I'm taking a drug that inhibits 2D6 (with or without the deficiency), plus I'm using a non-selective MAOI (30mg selegiline/day), I could be boosting my levels of NE, via the putative increased half-life of l-meth., to give me a bit of hypertension chasing the peak in plasma levels of l-meth. Selegiline is very extensively and rapidly metabolized in the gut by CYP3A4, and the primary metabolite is l-meth. This happens in just a couple hours or so. So, if I take my first dose around 8 AM, the second around 2 PM, and I'm hypertensive in the early afternoon all the way until around midnight (which, it turns out, I was)...well, maybe that's the cause.
> >
> > Hmmm. Pseudopheochromocytoma caused by a drug interaction of diphenhydramine and selegiline (l-methampetamine)?
> >
> > As it is, I have some pretty bad anticholinergic symptoms when I take diphenhydramine (dry mouth esp.), so my doctor and I, for reasons unrelated to the above, thought low-dose neurontin might be a preferable sleep-aid, since that also may have a bit of an anxiolytic effect, which gawd knows I could use these days. I just got the new script today. Maybe I should look at the metabolism of neurontin before I fill it...
> >
> > Just as an aside, it was actually my pdoc (and another pdoc at McLean) who floored me with their near-immediate assumptions that my problems were psychosomatic. My pdoc actually probed rather deeply into my "encounter" with this other woman, who I confess I'm not thinking all that much about at the moment, one way or another, given my present concerns. She (my pdoc) was, and I'm not exaggerating, convinced in about five minutes, after I acknowledged I had developed a somewhat distressing crush on another woman (understandable, being rather involved with somebody as I am), that my symptoms were entirely psychosomatic. Throw in the parental abuse/abandonment issues...elementary, my dear. I predicted as much in my satire of an analyst above. I swear I am not making any of this up...in fact my great anxiety in the beginning was largely fueled by the anticipation of this hypothesis. It's just...so frustrating.
> >
> > Major disappointment, to say the least. Anyway, I dealt with it finally the way I often do with disputes: "With all due respect, I think you're wrong." Yes, I'm a pain in the ass, and I have the audacity to argue with medical specialists, which makes me an arrogant pain in the ass to boot. BUT, I have the "benfit" of having been me for some 31 years now, and psychosomatic illnesses, BDD or no BDD, ain't my bag. There's just no good reason to jump on that diagnosis, as far as I can see, and I refuse to until I've ruled out all else.
> >
> > > Hi Adam--
> > >
> > > I'm very sorry to read of your physical problems--hardly seems fair to get one big problem solved, only to be sandbagged with another, which threatens to unravel the solution to the first! Sorta seems like you're being toyed with.
> > >
> > > I believe that the name of the tumor you referred to is pheochromocytoma--easy to see why that didn't make it to long-term memory. The episodic nature of the cardiac symptoms you memtioned is characteristic of this type of tumor. If you're interested in reading more about this, a good place to start might be Medlineplus at:
> > >
> > > http://www.nlm.nih.gov/medlineplus/pheochromocytoma.html
> > >
> > > If these Sxs were solely due to selegilene, you'd think that your BP spikes (which, though measurable, still fall in the borderline area of hypertension) and runs of tachycardia would parallel the drug's serum concentration peaks.
> > >
> > > I wouldn't take seriously your doc's inclination toward psychogenic explanations. I believe that this is a common reaction of any non-pdoc to any unclear symptomology in a patient with a positive psych history. For example, many years ago I had a stroke paralyzing the left half of my body. The neurologist assigned to me (I didn't have a PCP then) announced to the students he was conducting on rounds that my paralysis was most probably psychosomatic, because I didn't have a severe headache or an abnormal EEG. I told him (and his minions) that I thought that this was, unfortunately, even less likely than the notion that he had either compassion or competence, and that he was fired. As you seem to have discovered from your prior medical encounters, sometimes, there are just no payoffs for putting up with fools.
> > >
> > > Hoping that fate gives you a break---medlib
poster:Adam
thread:69963
URL: http://www.dr-bob.org/babble/20010809/msgs/74331.html