Posted by Ktemene on January 12, 2005, at 20:41:22
In reply to Re: My friend w/ PD had hypertensive crisis- selegili » King Vultan, posted by KaraS on January 11, 2005, at 13:47:24
> > > My friend takes selegiline for Parkinson's Disease. She usually takes 10 mg. a day but recently her doctor told her she could take 15 mg. Unfortunately he never told her anything about the diet or the risk of hypertensive crisis. We were talking on the phone tonight and I mentioned that I'm considering an MAOI and we discussed the risk of hypertensive crises. She said that sounded like what happened to her the other night. She had just thought that it was a horrible migraine. She had eaten cheddar cheese earlier in the day. Since she didn't know what was happening to her, she didn't go to an emergency room or take anything to lower her blood pressure. If we hadn't spoken, who knows how many times this might have happened to her.
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> > > She had bought a big hunk of cheddar cheese and would definitely have eaten it again. I'm just so angry that she had to go through that and that her ignorant doctor didn't warn her. This is one of the major PD medications and he doesn't know enough to warn his patients about the MAOI diet?
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> > The tyramine potentiation studies I've seen suggest that even 20 mg selegiline is much less problematic than 60 mg Nardil or 20 mg Parnate. I'm a little surprised she had this much of a reaction, but tyramine sensitivity does vary widely among individuals. As I recall, the Parnate study I saw suggested one person may require only 2-3 mg tyramine to boost their BP 30 mm Hg while on 20 mg Parnate, while another person taking the same amount of Parnate might need to ingest 10 times that amount of tyramine (20-30 mg) to experience the same effect.
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> > Cheddar cheese is just chock full of tyramine, and eating large amounts of it can sometimes cause headaches and other problems even in people who are not on MAOIs. However, even on 10 mg selegiline, I think it makes sense to limit one's intake of extremely tyramine rich foods like this one (I would not recommend entering a sauerkraut eating contest, either).
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> There is definitely a lot of individual variation. She never did have any problems at 10 mg. It was only going up to 15 that seemed to cause her problems. Yet I've heard of others who have had problems at only 5 mg. of selegiline (if one post here at PB was accurate). It's important to know which type you are and to take into account which medication you're on and the amount you're taking. Of course it's best to have your doctor tell you about the risks to begin with!!!
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> KHi Kara,
I was sorry to hear about your friend, and shocked that her doctor was so careless. To my mind it would be great if some civic-minded person were to take her doctor into a sound-proofed room and kick him in the behind until his nose bleeds. Has your friend had her blood pressure checked lately? It crossed my mind that a doctor that careless might well be careless about keeping track of general non-Parkinson's health conditions that might effect how she reacts to medicines. If your friend has high blood pressure already, she might be more sensitive to even a small tyramine-induced spike in blood pressure. But then she could have perfectly normal blood pressure and just have the bad luck of being unusually sensitive, since, as you say, there is a lot of individual variation. I looked up one of Adam's posts about it (and copied it below); that may be the post you mentioned about sensitivity even at 5mg Selegiline. Speaking of kicking people in the behind, I wish somebody would give Adam an ...ahem...fundamental incentive... to drop us a line!
Ktemene
Re: Report of success: Selegiline: alernate MAOIPosted by Adam on March 17, 2001, at 22:24:14
http://www.dr-bob.org/babble/20010310/msgs/56813.htmlIn reply to Re: Report of success: Selegiline: alernate MAOI, posted by Mr. Scott on March 16, 2001, at 17:14:17
> Do you think there is a "SAFE" dosage to take selegeline WITH an SSRI?In theory, there shouldn't be a problem with doses where there is no inhibition of MAO-A, which one would think is 10mg or lower. From what I've read, there is complete or near-complete inhibition of MAO-B at doses around 5mg/day, and once you are up in the 10mg/day range, you've got complete inhibition of MAO-B, and a small amount of inhibition of MAO-A. You have to be mindful of the fact that the "specificity" of selegiline is really just a differential affinity for each isoform of MAO. Most dose-response curves for drugs are typically "sigmoidal", or S-shaped (and can be fit "parametrically" pretty well, in most cases, to the "Hill equation", though there are usually better models for specific drugs). You have a long range on the low and high ends of the curve where there is little or no added effect for an increase in dose, and then somewhere in between the effect shoots up, and in this dose range, you get a near linear increase of effect per increase in dose. So you want to know, what's the real EC50 (the dose where 50% of inhibition occurs) for MAO-A? That dose is one you want to stay away from, because anything close to that (within about a log or half a log), or much higher, could give you a pretty significant inhibition of MAO-A. The trouble is, I'm not sure if the answer to that is known. If someone has done a dose response curve for MAO-A in people, I'm not aware of it, and there's little real information for someone to work with to inform such a decision (to augment an SSRI with selegiline or visa versa), if there is no such info. And, unfortunately, that value (EC50 for MAO-A) could vary quite a lot from person to person, perhaps because they are taking a drug that inhibits selegiline metabolism, or they are deficient in a drug-metabolizing enzyme (neither of which may be easy to ascertain).
I was once under the impression that, at 5mg/day selegiline, one should have no problem taking an SSRI concurrently, and you would still see complete or near-complete inhibition of MAO-B. I've revised my thinking, especially since I've been experimenting with small-molecule drugs a lot a work, and seen some of the variation that can occur in dosing, even among inbred animals. It may be entirely possible (and I know some people do it, as there are a few papers from Europe describing the practice) to take low-dose selegiline and an SSRI concurrently, and suffer no ill effects. However, there may be real risk, which is impossible, as far as I can see, to assess beforehand, of serotonin syndrome, which, as we all know, could be deadly. Given even remote odds, I seriously doubt you will find a physician on American soil who would go along with the experiment. Maybe I'm wrong, but, given the risks, I don't think this is a viable approach, for both health and legal reasons.
poster:Ktemene
thread:440536
URL: http://www.dr-bob.org/babble/20050108/msgs/441355.html