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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by Squiggles on August 30, 2001, at 15:26:45
You must have your finger on the trigger.
OK - thanks - that's good practical advice;
question remains: is clonazepam as an
anticonvulsant different in its chemical
structure?Squiggles
Posted by SalArmy4me on August 30, 2001, at 15:31:03
In reply to But are they different?, posted by Squiggles on August 30, 2001, at 15:26:45
Maybe Cam can answer that.
> You must have your finger on the trigger.
> OK - thanks - that's good practical advice;
> question remains: is clonazepam as an
> anticonvulsant different in its chemical
> structure?
>
> Squiggles
Posted by Cam W. on August 30, 2001, at 17:04:49
In reply to But are they different?, posted by Squiggles on August 30, 2001, at 15:26:45
Squiggles - Surprizingly, there is a lot of debate on this question. Some researchers say that the only difference between benzodiazepines is in their pharmacokinetics (ie. absorption, distribution, metabolism, and excretion).
A major distinguishing feature between all benzos is their fat solubility; their ability to be taken up by fat cells and the ease with which they are released. The more fat soluble benzos are released slower, thus have longer half-lives.
Also, since all benzodiazpines bind to the same area in the GABA receptor complex, it is said that they should all have the same action. The differences seen in their actions is due to the ability of certain benzos to enter areas around specific brain structures; again relating to fat solubility (related to the polarity - ionized state - of the molecule). Stimulating GABA receptor complexes (thus slowing neuronal electrical transmission via sodium influx into nerve cells) by specific benzos in specific brain structures would cause different effects between the benzodiazepines.
To complicate things (if that is possible), one must also consider metabolism. There are (at least) 3 main ways benzodiazepines are metabolized (oxidation, glucuronide conjugation, and nitro-reduction). The metabolism mainly occurs in the cytochrome-P450 system of the liver. As we age, we are less able to oxidize or nitro-reduce, but conjugation reactions seem to remain at normal levels. So, when looking for a benzo for the elderly, the route of metabolism is a concern. Lectopam™ (bromazepam); Serax™ (oxazepam); and Restoril™ (temazepam) are probably the best for the elderly.
I hope that this is not too confusing. The are other minor differences, but these are the main ones (and my wife wants to use the computer). - Cam
Posted by Squiggles on August 30, 2001, at 17:28:21
In reply to Re: But are different benzos different? » Squiggles, posted by Cam W. on August 30, 2001, at 17:04:49
> Squiggles - Surprizingly, there is a lot of debate on this question. Some researchers say that the only difference between benzodiazepines is in their pharmacokinetics (ie. absorption, distribution, metabolism, and excretion).
>
> A major distinguishing feature between all benzos is their fat solubility; their ability to be taken up by fat cells and the ease with which they are released. The more fat soluble benzos are released slower, thus have longer half-lives.
>
> Also, since all benzodiazpines bind to the same area in the GABA receptor complex, it is said that they should all have the same action. The differences seen in their actions is due to the ability of certain benzos to enter areas around specific brain structures; again relating to fat solubility (related to the polarity - ionized state - of the molecule). Stimulating GABA receptor complexes (thus slowing neuronal electrical transmission via sodium influx into nerve cells) by specific benzos in specific brain structures would cause different effects between the benzodiazepines.
>
> To complicate things (if that is possible), one must also consider metabolism. There are (at least) 3 main ways benzodiazepines are metabolized (oxidation, glucuronide conjugation, and nitro-reduction). The metabolism mainly occurs in the cytochrome-P450 system of the liver. As we age, we are less able to oxidize or nitro-reduce, but conjugation reactions seem to remain at normal levels. So, when looking for a benzo for the elderly, the route of metabolism is a concern. Lectopam? (bromazepam); Serax? (oxazepam); and Restoril? (temazepam) are probably the best for the elderly.
>
> I hope that this is not too confusing. The are other minor differences, but these are the main ones (and my wife wants to use the computer). - CamThank you Cam
for taking the time to present the sides of this
controversy. Yes, I have heard all these arguments,
though I will not say I am familiar with pharmacokinetics;
and they all point to the "subjective" variance in responses.But I suppose, to repeat myself (sorry) what I am
asking is - did Roche make the drug clonazepam different,
in order to produce an anticonvulsant. How would they
justify the marketing of this drug thus if it is not
chemically distinct from the others?I can testify that the experience of withdrawing from
this drug is the mirror effect of not having a
convulsion or seizure, i.e. it felt like a seizure.But as this is common to all benzos it is hard
to tell if it is specific to clonazepam.Sorry to press the point - you need not pursue
it if it is of no interest.tx
Squiggles
Posted by Cam W. on August 30, 2001, at 17:48:32
In reply to Re: But are different benzos different?, posted by Squiggles on August 30, 2001, at 17:28:21
Squiggles - Sorry, sometimes I get bogged down in the science and miss the question.
Technically, a molecule is a molecule is a molecule. The Roche brand of clonazepam is the same molecule as the generic version. What does change is the binders and excipients; the stuff they put in to color the tablet and hold it together. Sometimes people can have an allergy to one of these; sometimes the generic product does dissolve as well as the brand name; sometimes the generic company only does minimal quality control.
The above are supposed to be controlled for by the government (at least in Canada), but I do here people say that the generic version of Valium is not as good (but I don't know why - some of it could be psychological). I have not heard of problems with clonazepam, though.
A way around the brand/generic problem, is to find an ultra-generic version of the drug. An ultra-generic company is one set up by the brand name company to sell a generic version of their product. In Canada, the biggest ultra-generic company is Alti-Med. Rivotril™ and Alti-Clonazepam™ come out of the same vat, but have different markings pressed into them. Therefore, they are essentially identical.
Hope that this answers your question. - Cam
Posted by Squiggles on August 30, 2001, at 17:53:36
In reply to Re: But are different benzos different? » Squiggles, posted by Cam W. on August 30, 2001, at 17:48:32
> Squiggles - Sorry, sometimes I get bogged down in the science and miss the question.
>
> Technically, a molecule is a molecule is a molecule. The Roche brand of clonazepam is the same molecule as the generic version. What does change is the binders and excipients; the stuff they put in to color the tablet and hold it together. Sometimes people can have an allergy to one of these; sometimes the generic product does dissolve as well as the brand name; sometimes the generic company only does minimal quality control.
>
> The above are supposed to be controlled for by the government (at least in Canada), but I do here people say that the generic version of Valium is not as good (but I don't know why - some of it could be psychological). I have not heard of problems with clonazepam, though.
>
> A way around the brand/generic problem, is to find an ultra-generic version of the drug. An ultra-generic company is one set up by the brand name company to sell a generic version of their product. In Canada, the biggest ultra-generic company is Alti-Med. Rivotril? and Alti-Clonazepam? come out of the same vat, but have different markings pressed into them. Therefore, they are essentially identical.
>
> Hope that this answers your question. - CamThanks Cam,
I guess it's the binders or something - I doubt
it's the colour or filler - believe it or not
I looked it up and it's magnesium powder but
not enough to make a difference.Sigh
Thank you for your expertise.
Squiggles
Posted by Cam W. on August 30, 2001, at 19:40:29
In reply to Re: Roche calls it an anticonvulsant?, posted by Squiggles on August 30, 2001, at 17:53:36
Squiggles - All benzodiazepines are anticonvulsants, to some extent, especially the fat soluble, long-acting ones like diazepam (Valium™) and clonazepam (Rivotril™/Klonopin™).
The neurotransmitter GABA (gamma-amino butyric acid) is an "inhibitory neurotransmitter". It inhibits the release of other neurotransmitters (serotonin, dopamine, norepinephrine), thus slowing electrical transmission in nerve cells. The slowing of nerve cell conduction is calming, and thus stops the spontaneous firing of nerve cells, seen in convulsions.
Benzodiazepines facillitates the binding of GABA to the GABA receptor complex (causes a conformational change in the GABA receptor complex, so that GABA binds to it more readily).
- Cam
Posted by paxvox on August 30, 2001, at 19:58:20
In reply to Re: Roche calls it an anticonvulsant? » Squiggles, posted by Cam W. on August 30, 2001, at 19:40:29
Cam, Cam knows the stuff! You all need to pay attention when you see a Cam W next to a post.
PAX
Posted by Squiggles on August 30, 2001, at 20:05:20
In reply to Re: Roche calls it an anticonvulsant? » Cam W., posted by paxvox on August 30, 2001, at 19:58:20
> Cam, Cam knows the stuff! You all need to pay attention when you see a Cam W next to a post.
>
> PAX
Pax,He sounds eminently brilliant. Is he
a doctor or something?Squiggles
Posted by Cam W. on August 30, 2001, at 20:49:56
In reply to Re: Roche calls it an anticonvulsant?, posted by Squiggles on August 30, 2001, at 20:05:20
Please guys, I'll get a big head. Then I'll have to buy the economy size Vasoline to grease my head, so that it will fit through the door. This stuff is,...er was, my job, until recently. What can I say, "drugs are my life". - Cam (BSc Pharmacy).
Posted by Squiggles on August 30, 2001, at 21:02:33
In reply to Re: Roche calls it an anticonvulsant?, posted by Cam W. on August 30, 2001, at 20:49:56
> Please guys, I'll get a big head. Then I'll have to buy the economy size Vasoline to grease my head, so that it will fit through the door. This stuff is,...er was, my job, until recently. What can I say, "drugs are my life". - Cam (BSc Pharmacy).
LOL - Yup - Drugs are the answer.Squiggles
Posted by Tony P on August 31, 2001, at 1:29:19
In reply to Re: Roche calls it an anticonvulsant?, posted by Squiggles on August 30, 2001, at 21:02:33
> > [snip]. What can I say, "drugs are my life". - Cam (BSc Pharmacy).
>
>
> LOL - Yup - Drugs are the answer.
>
> SquigglesOr, as we say in certain mutual support groups:
"Sought through prayer and medication to improve our conscious contact...."
Tony
Posted by Tony P on August 31, 2001, at 1:52:37
In reply to Re: Roche calls it an anticonvulsant? » Squiggles, posted by Cam W. on August 30, 2001, at 19:40:29
Despite my previous humorous (I hope) comment, I have an immediate and serious interest in this. I'm on a reasonably low dose of clonazepam right now. I have however been hooked on short-acting benzodiazepines in the past, most recently about 10 years ago.
I have now been taking low doses of Clonazepam (.5-1.5 mg. per day) off and on for about 3 months, and am currently on a (hopefully) temporary regime of .5 prn in the daytime and .5-1.0 mg at night, for agitation and insomnia while I adjust to Welbutrin (day 7 today and things are going really well). A side benefit is presumably some seizure protection - I'm not high risk, but did have a couple of seizures 25 years ago withdrawing from valium & alcohol, partly also precipitated I'm convinvced by the Chlorpromazine my pdoc prescribed at the time, not knowing that is a fairly common exacerbating factor in withdrawal seizures.
Returning to the present day, I don't want to stop the clonazepam, which is serving a useful pupose, and I am sticking to the Dr's limits or less, but I'm worried: Am I setting myself up for an unpleasant withdrwal at this dosage and time frame - maybe a few more weeks?
Tony P
> Squiggles - All benzodiazepines are anticonvulsants, to some extent, especially the fat soluble, long-acting ones like diazepam (Valium™) and clonazepam (Rivotril™/Klonopin™).
>
> The neurotransmitter GABA (gamma-amino butyric acid) is an "inhibitory neurotransmitter". It inhibits the release of other neurotransmitters (serotonin, dopamine, norepinephrine), thus slowing electrical transmission in nerve cells. The slowing of nerve cell conduction is calming, and thus stops the spontaneous firing of nerve cells, seen in convulsions.
>
> Benzodiazepines facillitates the binding of GABA to the GABA receptor complex (causes a conformational change in the GABA receptor complex, so that GABA binds to it more readily).
>
> - Cam
Posted by Cam W. on August 31, 2001, at 2:19:05
In reply to Re: Roche calls it an anticonvulsant? » Cam W., posted by Tony P on August 31, 2001, at 1:52:37
Tony - You will have to taper the dose of clonazepam when you (&/or your doc) do decide to stop taking it (ie. when the initial start-up side effects of the Wellbutrin begin to wane, and the potential antianxiety action of Wellbutrin kicks in). The half-life of clonazepam is fairly long, so I doubt that you will have to go diazepam (Valium™) when you are tapering.
Manufacturers recommend that if benzos are used for only 2 weeks, a tapering of the dosage should be done, to avoid any unpleasant withdrawl symptoms.
I would hazard a guess that the chlorpromazine was a major factor in lowering your seizure threshold, and the alcohol and Valium withdrawl triggered the seizures. I sincerely doubt that weaning from the clonazepam would cause Wellbutrin-induced seizures, but a very slight risk is still there.
You are taking a relatively low daily dose of clonazepam, as well, which also makes it easier to stop. If the clonazepam is being used judiciously, as you are saying (ie. not increasing the dosage &/or mixing it with alcohol, other anything else which may lower seizure threshold) you should have little problem weaning from the drug when the time comes.
I would recommend that the longer you stay on the clonazepam, the longer the weaning process should be. Have your doc follow you closer than normal during the weaning process. An objective eye on the situation is always useful.
I hope that this answers your questions. - Cam
Posted by Tony P on September 1, 2001, at 1:27:05
In reply to Re: Roche calls it an anticonvulsant? » Tony P, posted by Cam W. on August 31, 2001, at 2:19:05
Thanks, Cam, that is very helpful.
I stepped the Wellbutrin up to 150 2xdaily today, according to plan. The worst of the anxiety side effects at the first level have subsided quite quickly, so I would not have anticipated staying on the clonazepam much more than a week or two, except that I have been having considerable sleep problems for months, which the Serzone I was taking was no longer helping. So I may be on it a month or so. I will talk to my MD about tapering at our next appt.
He has also given me Zopiclone (7.5) to help with the insomnia, so I have two strings to my bow there. Lately, and esp. with the WB, I have trouble both not falling asleep and waking up in the middle of the night. I am hoping that as I get more healthy generally - with the help of the extra energy from the Wellbutrin - and detox from the OTCs I was self-medicating with, the sleep problems will at least improve.
Tony
> Tony - You will have to taper the dose of clonazepam when you (&/or your doc) do decide to stop taking it (ie. when the initial start-up side effects of the Wellbutrin begin to wane, and the potential antianxiety action of Wellbutrin kicks in). The half-life of clonazepam is fairly long, so I doubt that you will have to go diazepam (Valium™) when you are tapering.
>
> Manufacturers recommend that if benzos are used for only 2 weeks, a tapering of the dosage should be done, to avoid any unpleasant withdrawl symptoms.
>
> I would hazard a guess that the chlorpromazine was a major factor in lowering your seizure threshold, and the alcohol and Valium withdrawl triggered the seizures. I sincerely doubt that weaning from the clonazepam would cause Wellbutrin-induced seizures, but a very slight risk is still there.
>
> You are taking a relatively low daily dose of clonazepam, as well, which also makes it easier to stop. If the clonazepam is being used judiciously, as you are saying (ie. not increasing the dosage &/or mixing it with alcohol, other anything else which may lower seizure threshold) you should have little problem weaning from the drug when the time comes.
>
> I would recommend that the longer you stay on the clonazepam, the longer the weaning process should be. Have your doc follow you closer than normal during the weaning process. An objective eye on the situation is always useful.
>
> I hope that this answers your questions. - Cam
This is the end of the thread.
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