Posted by PaulB on July 1, 2001, at 20:30:38
In reply to Re: Benzodiazepine Tolerance » rmshed, posted by Elizabeth on June 30, 2001, at 1:49:00
> > Paul: My experience with benzodiazepines has been fairly text book. I maxed out several years ago taking 4mg of Xanax per day. That was considered a theraputic dose for me. It was hard to taper down to 2.25 mg per day that I am on now.
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> I guess I'm confused. *My* textbooks all say that panic and anxiety patients *don't*, as a rule, develop tolerance to benzos. But it sounds like you kept needing ever-increasing doses. Or am I reading you wrong?
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> > I read in a book called "Anxiety and Phobia Handbook" that the tolerance may be down in the liver.
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> I'm not convinced. Tolerance is usually thought to be centrally mediated, a result of receptor down-regulation. Also, people who are tolerant to, say, Xanax, don't have cross-tolerance to other drugs whose metabolism is mediated by the same enzymes.
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> > I have a very low level of GABA production and that it also takes awhile for the brain to produce more GABA.
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> Xanax doesn't increase the amount of GABA; it makes GABA more effective at what it does.
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> > Although most of this is way over my head, I know understand about the need to increase benzodiazepines.
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> Most anxiety patients don't need to increase their dose, actually. I never experimented with long-term round-the-clock benzo use, myself (the closest I've come was taking Klonopin for a month at 4 mg/day and taking Xanax about once or twice a week for six months or more).
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> > If I had it to do all over again, I would try to find another drug that works with anxiety and panic disorder, my body is dependent on benzodiazepines.
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> Dependence (the experience of withdrawal symptoms upon discontinuing benzos) is a normal response. It's not the same as tolerance, though.
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> -elizabethpaulB writes
I think there are elements of tolerance down in the liver and the the CNS. This was mentioned in my former post but to continue this thread I think Elizabeth and Rmshed's theories on the decreasing effectiveness of the benzodiazepines are correct. There are two mechanisms via which the pams can cause tolerance. Benzodiazepines cannot be metabolised in the liver if the enzyme that metabolises them has been inhibited by the drug(Tolerance 1). The drug however will build up in the liver, druft into the blood stream and into the brain. After a while and continuous exposure to the drug in the brain receptor sesitivity and number will inevitably decrease(Tolerance 2)
poster:PaulB
thread:68279
URL: http://www.dr-bob.org/babble/20010701/msgs/68661.html