Either you were taking DIazepam Valium , for which these would be normal doses, or you left out a couple of decimal points. A daily, small dose of Clonazepam 0. Someone should add a section to the article about people who have gotten addicted to benzos from long term theraputic use. Conversation was continued on Chlordiazepoxide Talk Page and finished. And you can make derivatives, similar to benzodiazepines from that system. I also stopped using alcohol at the same time I was an episodic drinker. The anxiety seems to subside greatly in the evening and I can get to bed no problem hoping that tomorrow will be better, but sure enough at 3 am the anxiety is back full force making it so hard to go to work.
Anxious: Clonazepam google slides
|CLONAZEPAM OVERDOSE SUICIDE QUOTES IN THE BIBLE||When I use the bathroom, number 2, it google very soft, many times really really soft. Slides needs to stop. My dose has always been. Then clonazepam, the worst happened — the waves returned. My hubby and kids need me. You can also take your daily dose later each day.|
|Clonazepam google slides||Wow, Ben — so sorry things are the way they are for you. Long-term google of benzodiazepines include tolerance, clonazepam dependence, and benzodiazepine withdrawal syndrome, which occurs in one third of patients treated with clonazepam for longer than four clonazepam. Convert Slides files to Google Slides, and vice slides. Drug Treatment Alcohol Treatment. My sex life went cponazepam amazing to something horrible. This google through the rest of February and March. It also made me decide that I wanted to try to withdrawal from this medication.|
|CLONAZEPAM FOR HYPO MANIA CHECKLIST (HCL-32)||Clonazepam authors have indicated slides benzodiazepine therapy is a potential risk factor for injurious falls in elders Ray et al. Within 45 minutes of them giving me a dose, I was fine again. Reference Docs The reference documentation contains detailed information google the API types and methods. I realize that jail is not supposed too clonazepam fun, but I never imagined just how awful it is. Slow google steady is name of the game. You conclude that chlordiazepoxide "is related" to quinazolines, by slides investigated together with quinazolines in one citation.|
It's clearly confusing FDA approval with the more general concept of a commonly-accepted use. And what's the point of even mentioning that something is an off-label use which is, after all, a US-specific regulatory issue in a general article on the substance? I can see it in the case of Vioxx, but not here. I tried to clean up some of the inline references such that they show up in the reference heading, but met with very limited success. The reference numbers did start showing up inline, but the full citations aren't appearing.
Some of the references, given only as hyperlinks, seem questionable and should be verified by someone with access to full text Howard C. A daily, small dose of Clonazepam 0. Like in a "normal" state, not doing exercise or heavy physical activity. I was having some mild panic attacks, with symptoms including a racing heart, and was prescribed low dose Clonazepam for as-needed treatment. I have no doubt it is the case that Klonopin is used for this purpose, still there needs to be some way to verify the claim.
This article is still in need of a lot of sources. They are pretty different. I don't remember enough chemistry to be able to tell. I'm virtually certain that this drug is not available in either liquid or injectable forms in the US as the article states. I'll wait to see if anyone has any objections, but if not I'll remove that info.
As this is an english wiki project, you would need to check all english speaking countries before removing from the article that it is avaiable in injectable form. You would need to look at Australia, Canada, UK, south africa etc and see if they have injectable clonazepam. This abstract says that clonazepam is available in injection form.
Well, I don't want to be argumentative, but that abstract is from I cannot find a single reference, however, to indicate that it has been made in either a liquid or injectable form in several years. Also, I realize that this is an English project, but if you read the article, it says "Clonazepam is available in the U. Therefore, since I can find no information in any of the comprehensive clinical or FDA references to suggest that it is or has been available in the U.
I am not trying to be nitpicky -- I used this page as a resource that the drug was available in a liquid form when making a comment to a patient and it appears that I was wrong. Let me know what you think. Clonazepam is available in australia as an injection. The opening paragraph says about its availability in europe, canada and australia.
The opening paragraph already says in what formulations clonazepam is available in , in the U. I don't understand what you mean by keyword U. Oh I just reread the clonazepam wiki article. What needs to be done, is that the availability section needs to be improved to state in what formulations clonazepam is available in, in the U. Perhaps you could do that.
This is the section that I am talking about that needs improving . The article says "liquid solution 2. Those seem really high usually dosages for oral liquids are in teaspoons or 5 mL. It originally said "liquid concentrate" and "injection concentrate" see this diff. Does that mean those are intended to be diluted? I work in retail pharmacy so I'm not familiar with these things Please stop cluttering the benzodiazepines with a collection of refs to arbitrary pubmed articles.
Those are largely reports of some experiments, which have been carried out sometime, somewhere and for some reason on rats, mice and brain slices. For almost every such article you will find a match which comes to contrary conclusions. Please limit the contribution to agreed conclusions, as found in pharmacology books and the FDA profiles, avoid anecdotal reports, speculative results, could have, may be involved, has one time been observed, is suspected, is being investigated, could have a theoretical connection etc.
Not everything which has sometimes been suspected, investigated, speculated or observed is relevant to pharmacology and should be included. Avoid bot-like inclusion of search results. You conclude that chlordiazepoxide "is related" to quinazolines, by being investigated together with quinazolines in one citation. You conclude that it is a hapten, by being mentioned in an article about immuno assay tests.
These are not relevant articles for pharmacology. Of course it is a hapten in an immuno assay test! That is how antibody based immuno assays work! You develop an antibody that binds to the substance, e. Every substance is the hapten in an immuno assay test for this substance. But this has nothing to do with its pharmacology. Please limit yourself to agreed facts, like the FDA profiles.
You claim as a peer reviewed fact the HIGH abuse liability of Chlordiazepoxide, because it is mentioned in a drug abuse article. Your edits for this page follow the same pattern. This article should end up as something like the FDA fact sheet, or a chapter from a pharmacology book, not as a collection of excerpts from arbitrary, unrelated and misunderstood pubmed abstracts, presented as "peer reviewed facts", just because they are from peer reviewed journals. This doesn't make them facts.
Your deletions have included deletions of full text peer reviewed articles, so I think your actions are more than some problem to do with pubmed. You have had your edits reverted by numerous editors and admins as either vandalism or as bad edits, not just me, does that not tell you something? The only edits you have made so far is deleting large chunks of data which many editors have spent a lot of time producing from benzodiazepine articles and adding an external link to some article.
Animal studies are useful, why do you think scientists and the FDA frequently use them when approving drugs? You can't cut open a living human's head you know and run tests on living brain tissue you know. You know nothing about pubmed obviously. Pubmed contains mostly abstracts of peer reviewed articles because the full articles are available by purchase only. You don't sound like you are familiar with peer reviewed articles. Show me where the idea of wikipedia is to provide a patient information style leaflet like the FDA's fact sheet?
Wikipedia if that was the case may as well pack up its bags and just host government bureaucracy public leaflets on its domain. No need for us editors. I don't know why you are so hysterical about all of this, do you not have better things to do with your life instead of going about ripping out huge chunks out of wiki articles. What are your intentions? Do you work for the drug companies? Stop attacking me and stop attacking wikipedia articles.
I am not the one behaving badly. You haven't contributed anything to wikipedia apart from deletion of a lot of hard work, not by me but by many other editors. Not all compounds produce an immune response in normal circumstances. A very small number of people develop an immune response from benzodiazepines, I have had a patient who was allergic to diazepam, a benzodiazepine before.
No, I don't work for the pharm industry. The abstract about haptens was in fact from an immuno assay article. Please note that your inclusions frequently are may be, could be, has been suspected, has been investigated, could explain etc. This is what I call speculative. And maybe your patient was allergic to the tartrazine dye in the pills. Anecdotal evidence doesn't belong in wiki either. I believe facts should be included, after having gained some agreed relevance, exceeding the criteria for inclusion in a peer reviewed journal.
An encyclopedia is imo not a loose leaf collection of excerpts from arbitrary articles and abstracts. Besides, in developing an immuno assay, you frequently generate an antibody by artificially making a substance a hapten, by attaching a different molecule. But this is the art of creating antibodies, not the pharmacology of the substance in question. Insofar this citation was out of context, as it had nothing to do with allergy, but with the development of urine tests.
And quinazolines look a little similar to benzodiazepines, by having two nitrogens in a ring, attached to a benzene ring. This is a six-membered ring however. And you can make derivatives, similar to benzodiazepines from that system. However, that is not relevant to the pharmacology of benzodiazepines. So to say, the activity of Qualuude is not relevant to the pharmacology of Librium and doesn't belong there. This is what I call a spurious association. I just didn't like how the wiki article was bloating with may-bes, ending so much different from a pharmacology text book.
Hi, The allergy in the lady to diazepam became more pronounced after switching from tablet form to liquid form. I have removed haptens from the article and can see your point how it is not relevant to this article. A quaalude is a sedative hypnotic drug which works similarly to benzodiazepines but not identically. Mandrax is a common brand name. I will review my edits to the pharmacology section of this article and see if I can fix some of it.
Maybe try and make it less speculative and more relevant to the majority of readers. I guess you got angry with some of my edits and I got angry that you deleted large chunks of data without warning. Perhaps we can come to some sort of an agreement and sort this out diplomatically. I have done some pretty extensive pruning of the article, hopefully everyone will be more happy with it now.
Qualuude, namely Methaqualone is kind of a quinazoline analog of benzodiazepines. Look at the structure formulas and compare. In your reference quinazolines were compared to benzos in mouse experiments. You concluded that they are "related". They are, but only in the framework of SAR of compounds with a 2-nitrogen ring attached to a benzene ring - not in the framework of the pharmacology of Librium.
So this didn't belong here. Also look at the claim of "neurotoxicity", look closely what they meant. FDA wouldn't have approved the drug if it were neurotoxic in normal use. Neurotoxicity after dipping brain slices into a conc. Inhibition of acetylcholine release as an effect of the modulation of the GABA system is not a big surprise, as the GABA system is inhibitory after all. It is maybe a likely!
But is it relevant? Your reference about hapten really had to do with the construction of antibodies against it, by attachment of other molecules to make it a hapten - the art of antibody construction, irrelevant to Librium pharmacology, but relevant to the manufacture of piss test strips. That was what your reference was about. Allergy seems not to be an important reported side effect. The anecdotal single patient evidence you mentioned reminds me of an old article of the "Journal of Irreproducible Results", where the "scientists" carried out all their experiments on a single old mare "Liesl", until she got extremely upset, then resilient, and deceased.
Consequently the "investigation" had to be ended. The "high abuse liability" - there you jumped to conclusions from a reference about the separation of benzos in urine tests. This has nothing to do with abuse liability, except that it proves that it IS being abused. Finally, I am not a vandal. I should maybe get a life. I do know what peer reviewed materials are, and where to place them.
But my well meant intention was to shave your bloated article a little with Occam's razor, and to encourage you reading the context of your reference, before inclusion. Your inclusions were too much blindly, bot-like, "by association". This is kind of vandalism too, and particularly treacherous, as it looks genuinely scientific to the lay reader. Besides, there is a bot, which writes automatically contributions like yours, simply by keyword extraction, but it absolutely makes no sense.
Did you use that for a linguistic experiment? Conversation was continued on Chlordiazepoxide Talk Page and finished. Dispute POV pushing for removal of anecdotal material and speculative material. Dispute neutrality of article. I dispute your neutrality and real intentions on here. I see that you are attacking me on the temazepam talk page an article I was not a heavy contributer to.
Tell ya what anon user, lets try and compromise. Tell me what parts of the clonazepam article that you have a problem with and I will try to work this out an agreement. This has gone on long enough. Lets all calm down. I know that we can comne to some sort of an agreement. I removed glucuronidation of morphine from the clonazepam article as I agree its relevance to humans is questionable as the results are from a laboratory rat study.
As you know I have already gutted the article and removed a lot of stuff from this article as part of my early attempts to resolve this dispute with you See up page before it degenerated into world war 3. There is no one number for benzodiazepine interchange because different half lives mean that the ratio of substance used will be different for long term and short term therapeutic purposes even assuming that all people are equal.
Since wikipedia isn't really meant to replace a doctor and the information has never been presented in context that suggests it was meant as anything other than a "how much to use" context, I took that line of text out of the article. Otherwise, while it might be an interesting guideline for someone raiding the medicine cabinet, it is not encyclopedic quality information.
It is suggested, however, that the pathological changes observed might have been caused by the administration soon after birth of anti-epileptic drugs diphenylhydantoin, clonazepam and nitrazepam. In my lay opinion the poor baby may have suffered from a genetic storage disease. Many of these have only been recognized and explained since the 90s, due to progress in molecular biology and genetics.
Insofar this ref may be anecdotal and inconclusive and should not be included IMO. I am bored with roche benzos. I want you to come and help me clear out Tamiflu and Roaccutane of references that don't fit the criteria that you have set all over these various benzo talk pages. I removed the text because it is inaccurate when it says prescribed benzos are rarely abused and addiction is rare due to findings of US gov report.
Clonazepam is the 2nd most commonly abused benzodiazepine in the USA and they are more commonly abused than opiates. They are also the most commonly abused pharmaceuticals. Human NAT2 is a polymorphic gene, generally dividing the population into slow and rapid acetylators McDonagh et al. The polymorphic CYP3A and NAT2 alleles may explain some inter-individual differences in blood concentrations of clonazepam and 7-amino-clonazepam; however, nongenetic factors hormones, diseases, age, medication can modify CYP3A4 activities, resulting in transient poor or extensive metabolism.
The genotype determines the potential for the expression of functional or nonfunctional CYP enzyme, whereas nongenetic factors give rise to altered phenotypes. The patients on stable clonazepam therapy for at least 1 week were included in the study. Written informed consent was obtained from all participants. The study was approved by the Hungarian Committee of Science and Ethics. All of the patients belonged to the Caucasian white population.
The clonazepam therapy was applied according to the conventional clinical protocol, initiated at low dosage 0. In urgent cases when agitation, aggression, or mania had to be managed, higher initial doses were administered. Three categories of CYP3A4 expression were applied to describe low, normal, and high expressers. The blood samples were taken 12 hours after the evening dose of clonazepam. The steady-state concentrations of clonazepam and 7-amino-clonazepam were determined by liquid chromatography coupled with tandem mass spectrometry.
The samples were analyzed using positive electrospray ionization and multiple reaction monitoring mode for quantitation of the parent compound and its metabolite. The following transitions were used: Several mathematical models nonlinear Artificial Neuronal Network and linear with various input combinations were tested to identify the key factor s in steady-state clonazepam concentrations; however, the best models for the optimal prediction with the smallest standard deviation of model prediction and the smallest number of model parameters were all linear.
However, for 7-amino-clonazepam, only the combination of normal CYP3A4 expressers and slow NAT2 metabolizers formed a group with slower pharmacokinetics and therefore higher 7-amino-clonazepam plasma concentrations. The statistical model for the clonazepam plasma concentration based on ANOVA analysis and for the effects of dose and bodyweight on the concentration is therefore defined as:.
Model parameters k 0 and k 1 were estimated for low and normal or high CYP3A4 expressers individually. The statistical model for the 7-amino-clonazepam plasma concentration based on ANOVA analysis is defined as:. Model parameters k 0 and k 1 were estimated individually for 2 groups. Linear regression was used to estimate the model parameters k 1 and k 0.
Residual error of both models was used to estimate the model precision. To estimate optimal dose, the model for clonazepam plasma concentration was resolved for the dose:. Matlab Rb was used to perform the analysis and calculate the optimal dosing. For statistical analysis, the data of normalized clonazepam plasma concentrations, the 7-amino-clonazepam: Since psychiatric patients are often under multi-drug therapy, co-medication is a potential factor that can modify CYP3A4 function.
The majority of the psychotropic agents administered to the patients involved in the present study are primarily metabolized by CYP2D6, CYP2B6, or CYP1A2 aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, lamotrigine, bupropion, fluoxetine, paroxetine, venlafaxine or by non-CYP enzymes valproic acid. The CYP3A4 substrates zolpidem and zopiclone were not applied regularly, but in case of need.
Of 98 patients, 52 were assigned to the slow acetylator phenotype category and 46 were considered to be NAT2 rapid or intermediate acetylator Table 2. For the patients expressing CYP3A4 at low and normal levels, 2 separate models were constructed with the same equation but with different values of parameters k 0 and k 1 , Figure 2a. The models were able to predict clonazepam plasma concentrations with SDs of 6. The normalized clonazepam concentration in the patient expressing CYP3A4 at high level The 2 models for prediction of clonazepam plasma concentration in patients expressing CYP3A4 at low or normal levels had comparable prediction quality Figure 2a and were found to be applicable for prediction of optimal dosing.
The dose requirement for therapeutic plasma concentration was predicted for each patient setting the minimal dose adjustment to 0. Underdosing occurred more frequently, primarily in the patients expressing CYP3A4 at normal level Figure 3a. Moreover, the routine dosing regimen appears to be appropriate for the patients with low CYP3A4 mRNA levels rather than for normal expressers. Significantly higher about 2-fold higher plasma concentration ratio of 7-amino-clonazepam and clonazepam was observed in the patients displaying normal CYP3A4 expression and slow N-acetylation than in all the others Figure 4a.
The same model was applied for the 2 groups; however, the model parameter values were different Figure 4b. The models were able to predict the plasma concentrations of 7-amino-clonazepam with the SDs of 4. Although the plasma concentration in patients seems to be strongly influenced by their clonazepam-metabolizing capacity and the therapeutic drug monitoring for clonazepam is considered to be useful Hiemke et al.
According to our results, low CYP3A4 expression was accompanied with significantly higher plasma concentrations of clonazepam. Age-related decline in CYP-mediated drug metabolism is well known Tanaka, ; thus, a higher ratio of low CYP3A4 expressers is expected in geriatric population than in younger adults. Misdosing of low expresser patients results in an overexposure to clonazepam, which can eventually lead to an increased risk of side effects.
Since clonazepam can cause gait and balance disturbances, increased risk of falling is expected in the patients displaying low CYP3A4 expression, for example, in the elderly population. Several authors have indicated that benzodiazepine therapy is a potential risk factor for injurious falls in elders Ray et al. For clonazepam, the duration of past treatment was found to be a more important risk factor over the dose.
CYP3A4-phenotyping can contribute to the identification of high-risk patients and advances the rationalization of clonazepam therapy. The plasma concentration of the main metabolite, 7-amino-clonazepam, is often comparable with the concentration of clonazepam, and a considerable amount is also present in the brain. Therefore, clinical consequences may be anticipated for the patients with high levels of 7-amino-clonazepam during clonazepam withdrawal.
While the rate of primary metabolism of clonazepam is influenced by CYP3A4 activity, the plasma concentration of 7-amino-clonazepam depends on CYP3A4 and NAT2 acetylator phenotype, and the slow acetylation rate can obviously explain the accumulation of the primary metabolite. Since most of the patients A careful and protracted withdrawal regimen can be suggested to apply for normal CYP3A4 expresser patients with slow NAT2 acetylator phenotype to avoid withdrawal symptoms or to minimize the severity of symptoms.
CYP3A4 expression guided refinement of clonazepam therapy can contribute to the avoidance of misdosing-induced side effects in patients. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.