I don't have the full time I need to answer this, I'll come back to this but basically in short, the saliva reference was to break down the sublingual formulations of alprazolam, lorazepam, clonazepam, etc.
I don't think that benzodiazepines require saliva to be metabolized.
It's a very interesting discussion, you should post up links to the studies your talking about. The study I'm looking at shows ORAL alprazolam tablets reaching faster peak plasma and higher peak plasma concentrations, the study claims that the two ROA's are therapeutically equivalent. which is a decent contributing factor behind my hypothesis.
Thirteen healthy volunteers received 1 mg of alprazolam, as the commercially available oral tablet, by sublingual and oral routes on two occasions in random sequence. Plasma alprazolam concentrations during 48 hours after each dose were measured by electron-capture gas-liquid chromatography. The peak plasma concentration after sublingual dosage was higher than after oral administration (17.3 vs. 14.9 ng/ml), and the time of peak concentration following sublingual administration was reached (1.17 vs. 1.73 hours after dose). However, these differences did not reach statistical significance. The mean total area under the plasma concentration curve for sublingual administration was slightly but not significantly larger than that following oral dosage (203.7 vs. 194.4 hr.ng/ml) and no significant differences between sublingual and oral dosage were found for elimination half-life (11.7 vs. 11.8 hours) or for clearance (86.4 vs. 92.4 ml/min). Thus, alprazolam absorption following sublingual administration is as rapid as after oral dosage on an empty stomach, and completeness of absorption is comparable. In clinical terms, sublingual and oral dosages of alprazolam are likely to be therapeutically equivalent. The sublingual route may be a useful alternative for panic disorder patients who cannot swallow pills or for those who do not have access to a liquid at the time of dosing.
(I'm sure I've posted this before, but I thought I'd post it again in inline quotes so we don't have to find links all over the place, let's post all our relevant sources here)
What they're saying is that the sublingual formulated tablets do not require water to break down. They're not saying anything about whether it needs water to be absorbed, metabolized, etc. In fact, they say that it can be taken with or without water with no statistically significant differences (IIRC, with water = 15 minutes faster Tmax)
I think you may have misunderstood me, I understand that you say saliva in in itself or the H20 is unnecessary for degradation of benzodiazepines, but only the acidity in the saliva. What confuses me though is the fact that the acidity is in the saliva, which in someway implicates it directly in the degradation of benzodiazepines. How does one separate the two from a kinetical stand point?
This is an excerpt from the handbook of neuropsychology:
"The above discussion has not taken into account the hydrophilic and lipophilic properties of the drugs [benzodiazepines] and their effects on the rate of absorption and distribution-important factors in the selection of anxiolytic drugs in the elderly. Drugs that are more lipophilic such as 2-keto agent diazepam will enter the brain more quickly, but also disappear in the body fat. Less lipophilic compounds such as the 3-hydroxy compounds (eg. lorazepam), are more hydrophilic and will produce clinical effects more slowly, but in sustained fashion (Shatzberg and Cole, 1986)."
So if this is correct, that some are indeed hydrophilic, what are the implications of this relative to sublingual administration?
Sublingual administration of alprazolam: a pharmacokinetic approach:
A rapid onset of drug action is desirable for patients experiencing panic attacks or episodes of acute anxiety. The aim of this single-dose, three-sequence, crossover study was to investigate the pharmacokinetics of the anxiolytic alprazolam after administration of a single 0.5 mg dose of the drug, in tablets designed for sublingual administration (Tranquinal sublingual; Laboratorios Bagó, test product, Ts) compared with oral (Ro) and sublingual (Rs) administration of 0.5 mg of alprazolam of a reference product (Xanax; Pharmacia Upjohn) manufactured for standard oral administration. Blood samples were taken at 0 (before) and 4, 6, 8, 10, 12, 15, 20, 30, 45, 60, 120, 180 and 240 min and 30 h after drug administration, and plasma concentrations of alprazolam were determined by high performance liquid chromatography. The area under the time-concentration curve (AUC) over 0 to 15 min (ng ml-1 hr-1) was 0.12±0.03 for Ts, 0.07±0.03 for Ro and 0.05±0.02 for Rs (P<0.05). The AUC0-4 h values were 22.09±1.96; 22.50±0.99 and 19.65±0.95 for Ts, Ro and Rs, respectively, and the AUC0-30 h values were 109.05±12.21, 121.30±4.82 and 111.28±4.87 for Ts, Ro and Rs, respectively. Cmax values were 6.79±0.85, 7.11±0.64 and 6.14±0.30 ng/ml for Ts, Ro and Rs, respectively, whereas the Tmax was 2 h for all three.The results suggest that measurable plasma concentrations of the sublingual test product are achieved more rapidly than with oral or sublingual administration of a standard reference preparation of alprazolam, which might have therapeutic advantages.
Are there any sources that you could share that discuss the pharmacokinetics of sublingual administration of benzodiazepines in detail? I have no journal access for the things I'm trying to enter.
I am no Physician, but I have been prescribed Clonazepam going on four years. My ROA has been 2-3mg each evening, sublingually, with no adverse effects noticeable. It's a generic, I believe Teva. Not nearly as nice as the real deal, but it does the trick. I've never sub'd Alprazolam, but either way, if it's not the environment e.g., cottonmouth(which is common with this ROA), cocktails, hygiene, etc...then I would gather somethings up with the batch. A guy I used to work with sub'd his and I never heard him complain of discomfort. Considering the OP has used this ROA before and had no negative side effects, I would return it for a replacement script, different batch or brand. Even if it isn't a bad batch, why risk it actually being bunk and being distributed to other patients? That sh*t is all too common in the Carteceutical industry. Ooops, I meant Pharma. Aaaannd....
Refer to tricomb's previous post for the write up on Alprazolam's oral/sub efficacy. It's nearly identical. I only sub my claz out of habit. Not for accelerated or heightened effect. Peace.
So just to clarify, are you now retracting the above statement? I'm pretty certain it is just the inactive ingredients in the sublingual tablets that in some (not all) cases disintegrate faster, it doesn't change the water solubility of the active drug itself.
Here is an interesting study on the bioavailability of lorazepam tablets: (the following is paraphrased)
1. Oral tablets taken orally in the fasting state
Time to peak: 2.37 hr
Absorption half-life: 32.5 min
Absolute systemic availability: 99.8%
2. Sublingual dosage of oral tablets in the fasting state
Time to peak: 2.35 hr
Absorption half-life: 28.5 min
Absolute systemic availability: 94.1%
3. Sublingual dosage of specially formulated sublingual tablets in the fasting state
Time to peak: 2.25 hr
Absorption half-life: 28.7 min
Absolute systemic availability: 98.2%
Mine and tricomb's point was not that there aren't valid reasons for sublingual use of benzos but that you can easily take most regular oral benzo tablets sublingually and that the main motivation behind pharmaceutical companies making special sublingual forms - as opposed to just admitting the regular tablets can be taken either orally or sublingually - is profit. And I stand by that opinion.
One drug for which this has been particularly apparent to me is zolpidem, which while not technically a benzo acts of benzo receptors. It is available in at least 1 sublingual form, various oral forms, sprays, etc. For me the sublingual form (only available as a brand name of course) is literally 15 times more expensive than the generic oral form. It's ridiculous. I am going to experiment and see if the oral tablets are effective taken sublingually.
Back to the original topic, I think that a mouth irritation from sublingually administered benzos is just a sensitivity to one or more of the inactive ingredients in the tablets or to the drug itself. I have a list of the ingredients lists for some common formulations of clonazepam and alprazolam for anyone interested in seeing what the differences are. It's interesting that - to my knowledge - there are currently no sublingual-intended forms of clonazepam or alprazolam on the market, only "orally disintegrating tablets" which are intended to dissolve on top of the tongue as opposed to under it and either be absorbed through the mouth and/or swallowed and absorbed as usual.
Mine and tricomb's point was not that there aren't valid reasons for sublingual use of benzos but that you can easily take most regular oral benzo tablets sublingually and that the main motivation behind pharmaceutical companies making special sublingual forms - as opposed to just admitting the regular tablets can be taken either orally or sublingually - is profit. And I stand by that opinion.
This has all been a very interesting read. Being a student yet (not for much longer!), my exposure to a diverse array of patients has been limited... despite that, I doubt to ill come across enough patients with a benzo Rx first, and whom administer sublingual second. So, without participating in a study, I dont expect to be able to qualify any risk of oral irritation. Just thought I would lend my finding in this single instance due to OPs complaint.
My patient never experienced any pain or discomfort despite the irritation I found via clinical examination, nor he/I had found any tissue sloughing which would have been the case of chemical burn. The amount and intensity of the erythema altered me enough that I had a periodontist (and was ready to page the pathologist) come take a look. They also were surprised at the color of the tissues, but was not particularly concerned other than to recommend monitoring it. I'll add that there was in fact little to no edema, except the slight amount of exacerbated gingivitis that was not found in other areas of his gingiva except for the area closest to his tongue aka where the pills had been placed.
From what I saw, even assuming this is an isolated reaction, I don't believe it would or will lead to any long-term damage or disease.
Again let me say that he had been in the midst of a benzo binge, and had taken quite a bit in particular prior to the dental appointment due to anxiety... and he did end up sleeping through his subsequent fillings.
I'm not sure of the manufacturer of the alprazolam, and I suspected it to be the contributor over the clonazepam because I had worked with him a LOT during periods of his clonazepam SL administration and had not noticed those signs.
He is also a methadone patient, and is Rxed the C-pam but not the A-pam. He had become uncomfortable enough with my concern and examination by the periodontist that he actually requested that I stop pursuing it, as he didn't want to confess the illicit use of the alprazolam to any other Dr. The periodontist grilled him about using it SL, as they (nor most) are aware that SL use is seemingly widely accepted and of no damaging consequence to most who do this.
While he was capable of excellent oral hygiene, I have reason to believe (benzo'd out) that he had not been taking good care of himself, oral hygiene wise and nutritionally.
Anyway, just some information to put out there. What I saw wouldn't have necessarily been an allergic reaction, but a hypersensitivity. At the end of the day, I chalk it up to being a combination of xerostomia (made worse by acute dry mouth from physiologic action of med and physical occupation of pill at exit of sublingual and minor salivary gland ducts), poor oral hygiene, and some sort of hypersensitive reaction to an inactive ingredient also complicated by abuse.
I'd think it behoove anyone to at least irrigate (swish) the area with water, especially those who may notice a similar sensitivity... and in that case, good oral hygiene, as well as dry-brushing the area for 30 seconds following use will clear the tissues of enough irritant to probably prevent problems.
Okay well I just read the OP and skimmed through but this happened to me the other week when I was sublingually taking alot of the these http://www.drugs.com/imprints/gg-258-633.html The skin on my tongue did the same thing like the top layer was dying and peeling off. I fixed this by letting it start to get soggy before i pressed my tongue down on it and hold it in place. This technique also makes it easier to keep all the pill sludge in one part of my mouth. When I sub benzo's I keep em in till there's barely any binders left or drug taste. But I hate sub-lingual suboxone I plug that or waterline it.(The only thing I like about suboxone is the taste)
So just to clarify, are you now retracting the above statement? I'm pretty certain it is just the inactive ingredients in the sublingual tablets that in some (not all) cases disintegrate faster, it doesn't change the water solubility of the active drug itself.
Here is an interesting study on the bioavailability of lorazepam tablets: (the following is paraphrased)
Mine and tricomb's point was not that there aren't valid reasons for sublingual use of benzos but that you can easily take most regular oral benzo tablets sublingually and that the main motivation behind pharmaceutical companies making special sublingual forms - as opposed to just admitting the regular tablets can be taken either orally or sublingually - is profit. And I stand by that opinion.
One drug for which this has been particularly apparent to me is zolpidem, which while not technically a benzo acts of benzo receptors. It is available in at least 1 sublingual form, various oral forms, sprays, etc. For me the sublingual form (only available as a brand name of course) is literally 15 times more expensive than the generic oral form. It's ridiculous. I am going to experiment and see if the oral tablets are effective taken sublingually.
Back to the original topic, I think that a mouth irritation from sublingually administered benzos is just a sensitivity to one or more of the inactive ingredients in the tablets or to the drug itself. I have a list of the ingredients lists for some common formulations of clonazepam and alprazolam for anyone interested in seeing what the differences are. It's interesting that - to my knowledge - there are currently no sublingual-intended forms of clonazepam or alprazolam on the market, only "orally disintegrating tablets" which are intended to dissolve on top of the tongue as opposed to under it and either be absorbed through the mouth and/or swallowed and absorbed as usual.
They must contain a really horrible filler it's not that complicated man. Some pills are known to contain horrible fillers even if you just swallow them. Think of them canadian OxyNeo's (thank the opiate gods that we now have generic oxycontin with the old formula made by like 8 companies now). Also I read about how the NEW NEW NEW NEW NEW NEWEST Opana, the ones after the stop sign ones from pain patients that they get so sick to their stomach from them and that its just about as bad nausea and puking from large doses of opiate regimen withdrawals. Heh, so much for wanting to IV them. Purdue doesn't seem to mind their Hydromorph Contins here which are easily abusable with a mortar and pestle, just like some morphine preparations are M-Eslons, Kadians...but we dont have oxymorphone here, so I imagine it's never purdue making Opana. Sorry for the huge tangent I just feel very informative tonight
The filler(s) responsible for the erythema in my patient, and the irritation/tissue sloughing (supposed) are still present crushed or not although it may spend less time in contact with tissues. Again, I believe it's a "hypersensitivity" to filler(s) acting as irritants. It's possible that some filler may even remain long enough to induce an immune mediated response, chemotaxis, interleukin-1, phagocytes to gobble up the foreign fillers, et al.
I question whether or not its actual tissue sloughing thats occurred in the two reports I read in previous pages. It may be, but it sounds more like fungal infection derived from xerostomia and acute poor oral hygiene causing plaques on mucosa that can be wiped off.
^This threads about benzos man, but yeah, to go out on a limb here, I'll say that the inactive ingredients in benzodiazepines are much more benign than those found in time released abuse proof mechanisms found in opioids.
Based on the inactive ingredients in my generic benzos, I can't find anything really that shouts concern to me. The docusate sodium looks like the only thing that could be somewhat irritating, but we have no idea about the quantitative concentration/make-up of the pills besides what's in them.
I snort my Xanax to get high And also to calm myself down I dont use them all the time.But I notice that when I snort these my nose burns so bad I am thinking they ass something maing it hard to snort and even worse to shoot.thats my guess
I personally just chew my xanax. They are small enough to not have much gross tasting fillers, maybe a drink of something afterwards but i find chewing them to kick in faster than sub even
Yer doc told you that? I know it's not water soluble; hence, snorting them or shooting benzos isn't efficient, especially given the fact yer snorting 99.9% filler. Unless you're using alcohol to IV which I personally wouldn't think is a good idea. Unless you had pure hospital grade alpraz and saline solution, otherwise there are way too many binders. And I keep hearing that they are fat soluble which to my understanding would mean that other than the alps made for sublingual wouldn't work. In fact I was under the impression all benzos were alcohol soluble. SWIM used to get clonazapam powder from china and would slow cook it with ever clear or the strongest alcohol they could find to make a liquid solution. So that's interesting it kicks in that fast for you with the pills. As far as your mouth, I've woken up and coughed up or had white chinks of skin/mucus in my mouth regardless of the manufacturer. But if you've only noticed it with that manufacturer and others on this thread have had problems with then I'd try a different rx.
True, we don't know the quantitative amount of any binder, but in the US FDA requires ingredients in both foods and drugs to be listed in quantitative order, so some inference can be made about the formulation. When I worked in genetic drug development that's where we started, with the innovator's formulation but with absolute qtys unknown. Some analytics helped us find a starting point. We'd play around with ratios, knowing the innovator's ingredients - sometimes we nailed it, other times we used alternate binders to the innovator's. Changing inactive ingredients doesn't matter to FDA, ex., in cases where an excipient is known to degrade the active cmpd, alter bioavailability, etc...
