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N&PD Moderators: Skorpio
What is the interaction between phenelzine and carbamazapine?
- Thread starter Middleway
- Start date
MagickalKat777
Bluelight Crew
This is most likely because phenelzine is an MAOI. MAOIs can increase blood levels of carbamazepine, which could be dangerous.
vanboy5
Bluelighter
Additionally, phenelzine and CBZ agonise similarly on GABA receptors... which leads me to believe in a possible result of neurotoxicity of some sort... sorry if this wasn't too helpful...
P A
Bluelighter
There were theoretical concerns about hepatic interaction due to phenelzine's hydrazine moiety. But that was quite a long while ago, and I sincerely doubt that it's of any significance.
http://www.ncbi.nlm.nih.gov/pubmed/7559374
http://ajp.psychiatryonline.org/cgi/reprint/147/3/367a.pdfMudeltakappa
Bluelighter
- Joined
- Oct 21, 2010
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- 84
Eh?
Phenelzine is a GABA-Transaminase Inhibitor, it doesn't have any direct effect on GABA receptors. And why would GABAergic + GABAergic = neurotoxicity?
Why would MAOIs increase blood levels of carbamazepine? Carbamazepine is not metabolized by MAO.
I believe PA has it right here... the concern is (was) hepatoxicity.Last edited:
MagickalKat777
Bluelight Crew
Well the literature for Tegretol says not to take it within 14 days of stopping an MAO inhibitor...
negrogesic
Bluelight Crew
Do at least some better research.......the contraindication here is rather clear. In some cases, it is not.
Tramadol for example, has all sorts of odd interactions, but has one very clear and simple one: Do not take tramadol with a serotonergic drugs (with some exceptions; mirtazapine, a strong anti-histamine and serotonin antagonist-inverse). It has virtually NO affinity for the SERT; in other words, it is not a re-uptake inhibitor of serotonin and can be taken with tramadol without risk of causing a hypertensive crisis.
Mirtazapine is honestly not a great anti-depressant, but its a WONDERFUL anti-histamine (the Ki for H1 is something like 1.5nM, very powerful) and the most potent appetite stimulant (also a very good 5-HT3 antagonist) I've come across, especially in concert with long acting opioids. It is also a very safe and powerful anti-emetic (I prefer it to the supposed first-line ondansetron), hypnotic, but not a great anxiolytic, and yes there is some definite dysphoria when during the first two weeks of treatment. I take 90mg a day (one dose, night) for appetite enhancing purposes and its H1 antagonism, but no I am not suffering from clinical depression.Mudeltakappa
Bluelighter
- Joined
- Oct 21, 2010
- Messages
- 84
Right, well, with phenelzine specifically its a hepatoxicity concern, as stated above. I don't know why all MAOIs would be contraindicated. Perhaps they do raise blood levels, I'm just saying I don't see the mechanism by which that would occur.
P A
Bluelighter
And the risk of combining of an anticonvulsant with an MAOI is...?
Carbamazepine/=tramadol. However, I assume that due to your atrocious reading skills, you were unable to differentiate the word Tegretol from tramadol. Congratulations, you look like a moron.
Aside from containing nothing but poorly transliterated content from the pertinent Wikipedia article on mirtazapine, that hearty accolade for Remeron had absolutely no relevance to the question asked nor, for that matter, anything else in this thread.
negrogesic
Bluelight Crew
I was well aware that I went off on a tangent, your right, I must be a more, I must have mistaken carbamazapine for its super close chemical cousin tramadol. You are obviously far smarter than I, and sound like a very large man. Its funny how I never hear such criticisms when people see me in person, my glare is enough to let them know of their potential fate. My physical size backs it up. But yes, obviously, I am a moron, and you, the arm-chair internet nerd, know and have experienced far more than a simple man such as myself.
How many people have you witnessed die from drug interactions? Are you a QME, and how many have you done? How many coroners incorrect toxicological finding's have you challenged and reversed? In one case, the M.E. (in his toxicological findings) cited Trazodone as a "narcotic analgesic" and ruled it to be an overdose. The young man died from a drug interaction.
This is the actual findings, male, 23 years old. Found deceased.
Below is a fragment of MY arguments after reviewing the deceased in respect to the suspicious internal abnormalities:
It's people like you who I hate treating, I let the other residents deal with them........
negrogesic
Bluelight Crew
Waste my fucking time, jesus.....
P A
Bluelighter
....woah. Negrogesic, I hate to ask such a banal question - especially on Bluelight for that matter - but uh...are you, like, high or something?
Carbamazepine bears no structural nor mechanistic relationship to tramadol. This not only makes you twice as wrong as you were before, it makes you look all the more idiotic. Or were you feebly attempting sarcasm? I honestly can't tell.
Mother of all that is fuck. You are one hefty, self-righteous douche. What could any of that simpering drivel have to do with the fact that you were thoroughly, embarrassingly wrong about such a simple topic as a drug-drug interaction? As mentioned above, it was your piss-poor skim-style reading and arrogant, wrongheaded criticism ["Do at least some better research.......the contraindication here is rather clear"] that landed you in a vat of steaming idiocy. And so within it you continue to flounder. Was your harrowing account of that man's overdose simply intended to disturb and shock me? Or perhaps to persuade me of something? I can promise you that it did neither, largely due to the fact that it had no relevance to anything discussed in this thread. It was a complete non sequitur. The OP asked a straightforward question in a single sentence that you seemingly have yet to actually read. Apropos:
The prompt raised an issue of ambiguity, as there doesn't appear to be any readily accessible explanation for why exactly Nardil and Tegretol are commonly listed as contraindicated, nor any well-known biochemical mechanism by which this combination could confer harm. Some people answered by providing feedback, some of it sensible and educational in nature. You promptly burst into the thread, let everyone know how stupid they were [Do at least some better research.......the contraindication here is rather clear], then rambled on about two completely unrelated substances - tramadol and mirtazapine, without even addressing the OP's question. Then, after being told off, you threw a little pissyfit and gave me what I suppose you thought was a profound wake-up call in the from of equally irrelevant rhetorical questions and a similarly discontiguous (and revolting) review of a unfortunate overdose. Thank you for that, though I confess that I reamin unclear what your fucking point could have been. If there even was one, that is.
So no, I may not be an EMT, nor a medical professional of any kind, but none of that changes the fact that you're still a total fucking moron. And still wrong. Furthermore, if I understand your hysterical post correctly, you appear to be some kind of practitioner - perhaps even a doctor. This is worrying to me. The dumb mistake that you made in conflating two completely different drugs (tramadol and carbamazepine...wtf?) in the context of a casual discussion, when coupled with the brash manner in which you responded to what you wrongly assumed was our error, leads to me to wonder whether I would ever want my life in the hands of someone as imbecilic as you. I sincerely hope to good fucking christ himself that you're just some obnoxious internet toughguy impersonating a medical professional in a ludicrous attempt to make a misplaced point, or simply not typical of others in your profession; because if I or anyone I love ended up in the care of someone as easily confounded (and obnoxiously brutish) as yourself, I would be seriously concerned for the prognosis.
Translation: "I'm too butthurt and mortified by the fact that I was shown up on teh intarwebz to admit that I was wrong, or am too oblivious to even realize how I was wrong in the first place. Now I'll just puff out my chest and let everyone know that I'm so much kewler and wiser than thou in the ways of the world. " And in the form of dull sarcasm, no less. Yawn.
negrogesic
Bluelight Crew
I dictate on my phone, and the voice recognition is good but not great. No, I'm not high, but I am by nature a very hyperactive person. My sarcasm was more than clear. For you to even think I actually believed that there was a chemical similarity between those compounds demonstrates some rather faulty logic/reasoning on your part, and an excess of time.
Those who know me here permit me to ramble on, even if I do go a bit off-topic. The bottom line, for the site in general, is harm reduction and education; I was using the tragic but preventable tramadol related death as an example of the perils associated with drug interactions (which, like clinical pharmacology, is not stressed enough in american medical schools). My c-pharm textbooks are full of errors and ideas that are decades old (which I've marked and sent to the editors for review/revision), and even the instructors are ignorant to what one would think is general knowledge.
Have I suffered from drug addiction? Certainly and rather notoriously; opioids. Fortunately, I never truly abused nor cared much for cocaine, amphetamines or alcohol; unlike opioids (for the most part) severe addictions to these drugs often leads to irreversible and marked cognitive impairment and the corresponding decrease in functioning.
Perhaps my example was long winded, but again, it was to demonstrate a point. KNOW your drug interactions, do not rely on a single source, and do the necessary research like the rest of us. If there is something that is beyond ones comprehension, then yes, ask in an appropriate forum. But do not post, "does X interact with Y" without your own due diligence, - or at least, not in this forum. This sub-forum is geared for advanced drug discussion, and this question would be better suited for the Basic Drug forum, which is now more advanced than OD. Unfortunately OD has devolved into a sort of social forum; in its inception this Advanced discussion forum didn't exist, but both Phreex and I did our best to field questions of an advanced nature (OD is what made this site blow up in terms of traffic). It was thankless, but I do not work in medicine for the money or gratitude. I do so at great expense, but thankfully it is one I can easily afford due, in part, to my business education and my unusual success in technical derivative trading. I do not want to do this as a career; I have too many other interests, and plan to retire very early, so I can spend time with my future wife and children, and do what I love (compose music, fly small aircraft, tinker around with my own humble laboratory and help those in need). Honestly, I prefer veterinary medicine, because of my love for other animals and their unspoken gratitude .
Medicine is simply a personal detour for me; a quest for knowledge only experience can reveal.
I wish we still had a Medical Q&A (we used to have one), I don't have the MCB/ O-chem mastery of the other members still remaining, but I can offer solid, wide-spectrum and experienced medical advice. I realize that there are liability issues, but I believe the need is there.
I am not a vindictive man, but how long would you like to be a member at this site? Spewing hate is certainly grounds for a permanent ban, so watch your words. There is no room for that on this site. Phreex and I built OD, were rather strict about removing those defamed the site and their fellow members. We also built an elite underground version (no longer in existence, aside from the advanced version), and called for the creation of this sub- forum. I hate to see it devolve, but so are the nature of things...
Again, dictated, not typed.
amanitadine
Bluelighter
Wow. Im am just thoroughly...confused. Is there some sort of collective insanity at work here? Just between reading through this thread and the "fluoride in my ssri" thread, negro has gone from being accepted into med school to practicing overnight! And courtesy of any sort has vanished ...threads are getting overran with verging on hysterical bashing, and it seems people are not even reading the posts to which they are responding. Wha????
Wait, is this just business as usual, and I'm seeing the world as it actually is for the first time? Heaven help us.
P A
Bluelighter
That's all good and fine, but that message was never made explicit until just now. Your first post wasn't addressed directly to the OP, and so was understandably mistaken as pompous derision for everyone else in the thread. It was that lack of clarity, not vitriol, that provoked my reaction. Your second post was equally nebulous and self-important, if not more so.
Also, to reiterate for the third time - the inclusion of
within your post's preface was the key impetus for my response, as this confident declaration is patently false. This was my primary contention in the first place, and remains as vehement as ever. Carbamzepine does not detrimentally interact with phenelzine. The contraindication here is not clear because the contraindication does not appear to exist outside of old textbooks and poor internet sources. You still haven't responded in the way of clarifying the aforementioned particular sentence, which forms the crux of the actual disagreement that you've determinedly persisted in neglecting to address.
Or your incredibly poor rhetorical writing skills. I mentioned that there was a possibility that you were being dully sarcastic, but your cryptic sentences precluded clarity. And how could my posting possibly indicate an "excess of time?"
The issue here never had anything to do with rambling, which is perfectly acceptable when kept coherent and within the bounds of relevant thread topics. But the latter condition wasn't fulfilled. Your entire first post in this thread was a complete non sequitur. When read verbatim, it consists of a condescending jeer (seemingly directed at everyone), a false dictum [the contraindication here is rather clear] followed by an unwarranted aside lauding Remeron as a reliable sedative and orexigenic. It contributed nothing to the thread, and contained a generalized affront that could easily have been interpreted as a sweeping criticism of everyone here. As a member of the "Bluelight Crew," one would think you'd have more regard for common posting practice and basic netiquette.
And yet again, the point has managed soar over your head with the deafening roar of a 747 jet aeroplane. Though I ventured this explanation in my last post, it's now clear to me that you truly did not read the original post, at least not with any sound comprehension. For your enlightenment, here it is:
The OP wasn't asking "lol I has dugrz can I taek??? rspnd pl0x," nor "does X interact with Y." S/he was inquiring as to why exactly the drugs in question were contraindicated, since there doesn't appear to be any overt explanation for the alarming proscription as stated on websites like drugs.com or book sources like my PDR. The ensuing discussion involved the examination of either plausible mechanistic explanations or literary citations indicating the putative reasons these two drugs could not be safely coadministered.
To repeat (in case your reading skills fail you again) the question was why and not whether the two drugs were contraindicated. The specialized knowledge base needed to adequately address the inquiry makes this an advanced topic, not a basic one. Therefore, this is the appropriate subforum for Middleway's question. In summary, no matter how many ways one twists your cryptic first post, it is invariably irrelevant and wrong.
That is all.
Oh noes, now a threat? And all that moral fingerwagging coming from a guy who referred to me as an 'armchair nerd.' Give me a fucking break.Mudeltakappa
Bluelighter
- Joined
- Oct 21, 2010
- Messages
- 84
I don't like all the namecalling and negativity going on here, but I'll just say that I agree with PA in the sense that necrogesic's reply was irrelevant and made no real sense in the context of the original post. Moving on....
P A
Bluelighter
Word. Case closed. Anyone dredge up anything else? I'm seriously interested in this one. Just about everywhere I've checked, CBZ is either listed as absolutely contraindicated with PLZ or goes completely unmentioned [and vice versa in the case of PLZ]. Nothing in between. This is either a serious medical error of commission or omission, and I'm curious to find out which.Last edited:
negrogesic
Bluelight Crew
I agree this has approached the absurd.........................
Oh, and I was acceptaced to various med schools many years ago, I did not reeply. I asked the same schools if the offer was still good; they made me retake the MCAT to show that my old 40+ school was not a outlier. I am a .iicensed PA in Vet-med, so they "fast-tracked" me. If you guys think I am fucked up, you should meet my peers....
MagickalKat777
Bluelight Crew
Wow, this thread has been thoroughly derailed. Here is an attempt at bringing the focus back to the topic at hand.
I found a paper that might bear some explanation - here is a quote from that paper.
"SIR: Carbamazepine is becoming increasingly popular as a
prophylactic and therapeutic agent in the management of affective
disorders ( 1). As its use increases, it is likely that it will
be used in combination with a variety of psychotropic agents,
including tricyclics, phenothiazines, lithium, and monoamine
oxidase inhibitors (MAOIs), and it is imperative that clinicians
know whether or not such combinations are safe. There have
been a few reports of a marked rise in carbamazepine levels,
with toxicity, as a result of the combined usc of carbamazepine
and isoniazid, which is an MAOI (2, 3). The possibility that this
interaction may occur with all MAOIs was negated by Joffe et
al. (4), who observed no interaction between carbamazepinc
and tranylcypromine (which belongs to the nonhydrazine
group of MAOIs) in their patient. However, there are no reports
to indicate whether this property is shared by others in the
hydrazine group of MAOIs, which includes isocarboxazid and
phenelzine, or is unique to isoniazid. We report here a patient
who was treated with a combination of carbamazepine and
phenelzine without induction of toxic blood levels or serious
adverse effects."
http://ajp.psychiatryonline.org/cgi/reprint/147/3/367a.pdf
So it would appear that that the combination being contraindicated was indeed born through an MAOI interaction as I posted earlier in the thread, though the interaction was specific to THAT particular MAOI, not all MAOIs in general.
This quote is particularly interesting and basically seems to further reinforce that idea:
"Nonetheless, because there is some evidence to suggest
that both the hydrazine and nonhydrazine groups of MAOIs
cause hepatic microsomal enzyme inhibition, which is the
principal route of carbamazepine metabolism (5), further
study of the potential pharmacokinetic interaction between
carbamazepine and MAOIs is needed before any firm conclusions
are drawn."
It seems to me that there simply wasn't enough research done on the subject so in the end, they just lazily stamped a drug interaction for all MAOIs and CBZ.Mudeltakappa
Bluelighter
- Joined
- Oct 21, 2010
- Messages
- 84
Nice find. Thanks for shedding some light.
