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Thread: Mechanisms Behind Paradoxical Reactions/Effects?

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    Mechanisms Behind Paradoxical Reactions/Effects? 
    #1
    I have been interested in this for quite some time after having my own personal experiences with PR's, but have never found an explanation to how drugs go wrong.
    For some examples what are the possible pharmological actions behind the following:

    Benzos causing excitability, insomnia, rage, convulsions, and rage;
    Sedative antihistamines causing hyperactivity and insomnia;
    Opiates causing hyperactivity and insomnia;
    and other "sedative" drugs such as trazodone, amitryptaline, gabapentin, and phenobarbital causing similar reactions.

    So how or why do these types of reactions happen? In addition to the sedatives mentioned above I'm interested in any other PR info on any other drugs anyone might have. Thanks.
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    #3
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    Quote Originally Posted by Regenesis2 View Post
    Sedative antihistamines causing hyperactivity and insomnia
    Whenever any drug is studied on humans, all adverse reactions must be reported. To report only the ones you expect to see would be bad science.

    What happens is that long-acting sedatives dicky with circadian rhythms. Eventually people will have difficulty falling asleep because they have slept too much. This gets reported, and thus all long acting sedatives will be said to potentially cause both somnolence and insomnia.

    Paradoxical reactions to short-acting benzos are due to very complex neurological processes I think. Possibly not well understood yet.
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    #4
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    There was a very famous case with triazolam, in which a elderly man murdered his wife in a rather gruesome fashion, and had no recollection of doing so.....

    Paradoxical reactions are seen most often with potent benzos such as triazolam, clonazepam, however can also occur with essentially any benzo (or any drug for that matter). I have seen rather strange reactions to IV midazolam, but oddly, not so much with IV/IM lorazepam. Paradoxical reaction is somewhat of a vague term, because it also seems to encompass bizarre behavior. Some of the more interesting and extremely bizzare behavioral side-effects occur with drugs like varenicline (chantix, yikes) and pramipexole (and similar RLS drugs). In the dispensing pamphlet for pramipexole it lists "compulsive gambling" as a side-effect. I suppose its not funny, but I think 'compulsive gambling' is a pretty hilarious side-effect........

    I have seen paradoxical reactions to lethal doses of pentobarbital (I used to work in veterinary medicine....euthanasia was virtually a daily procedure), but interestingly, I have yet to see a "true" paradoxical reaction to propofol. It has been reported, but I have not come across a case personally.......

    Also, I have yet to come across a paradoxical reaction (in humans) when using volatile vapors (generally sevoflurane, isoflurane is still used, but sevoflurane is far more prevalent). I have used halothane extensively in veterinary medicine, but never with humans (aside from playing around with it myself......wasn't fun).....
    Last edited by negrogesic; 01-03-2011 at 21:23.
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    #5
    I personally have paradoxical reactions to some meds first off opiates usually cause sedation in people but when i take a low dose say 10mg hydrocodone its almost as stimulating as 30mg adderall but if i take a 30mg adderall i can go to sleep on it(i have true add).Also benzos at low doses are like normal reactions say 1mg alprazolam but if i take like 2bars(4mg)i totally lose it and become almost violent.
    the problem with me is like alcohol when i am on xanax i get really confused to the point that i can forget where i am and then i end up getting mad and frustrated at everything around me. and the anger last about 24 hours afterwards.
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    #6
    Quote Originally Posted by negrogesic View Post
    There was a very famous case with triazolam, in which a elderly man murdered his wife in a rather gruesome fashion, and had no recollection of doing so.....



    I have seen paradoxical reactions to lethal doses of pentobarbital (I used to work in veterinary medicine....euthanasia was virtually a daily procedure), but interestingly, I have yet to see a "true" paradoxical reaction to propofol. It has been reported, but I have not come across a case personally.......

    Also, I have yet to come across a paradoxical reaction (in humans) when using volatile vapors (generally sevoflurane, isoflurane is still used, but sevoflurane is far more prevalent). I have used halothane extensively in veterinary medicine, but never with humans (aside from playing around with it myself......wasn't fun).....
    this reminds me speaking of propofol last year i had an upper and lower gi scope.
    the doctor told me he would be using propofol for sedation i guess.
    ALL i remember is him saying he was putting it in the iv next thing i know i wake up like wtf just happend and felt great but the doctor said when he gave it to me i started going crazy with panic and they had to increase the dose.so i might have hade a reaction to it.
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    #7
    ... -What happens is that long-acting sedatives dicky with circadian rhythms

    Although this is a valid concern and a good reason not to take these things so much, this is not what I was refering to. Sedative antihistamines like diph and hydroxyzine can make people instantaneously stimulated as opposed to causing instant drowsiness and sedation. I would compare the feeling to a 'meth-like' effect, though without enjoyable dopamine properties.

    also thanks negrogesic and psykeith for your responses. The articles on the dr. Hall site are really good. I've heard of people getting sedation from ritalin before too.

    Also on opiates I have read that thebaine is considered stimulating, but I can get stimulated from codeine and morphine too. I have also read that opiates increase effects of dopamine so that can explain the stimulation. When I do get stimulated from opiates, which does not always occur, it is very mild and usually I can sleep on them but get those instant intense and long lasting dreams.

    The PRs I got were from low doses of diazepam. I have a thought that maybe the drug lands on the receptor site and causes an 'inverse agonist' response. When i had them that is what the effect was like, as if I took an inverse agonist and the chloride channel was completely shut. I don't consider depression or behavior induced by lack of inhibition to be a PR based on my experience. My PRs were like being possesed and the altered function of the brain produced some really bizarre "seizure aura' like effects too. Considering the reduction in serotonin, norepinephrine, and dopamine caused by benzos, depression should and usually is considered a normal side effect of use. "Acting out" on benzos too is a different side effect and would likely occur for those who do the same during alcohol use, which I never do, I handle myself fine on alcohol minus the dizziness and vomiting.

    But, the sedative antihistamines still remain a total mystery and I cannot make any pharmological sense from it. Not even a guess.
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