# Taking drugs sublingualy = twice as more potent?



## A32 (Jul 2, 2011)

From wikipedia:

_However, many drugs are much more potent taken sublingually, and it is generally a safer alternative than administration via the nasal mucosa. Due to the high cost of pharmaceuticals, some people opt to split their pills and take them sublingually in order to obtain the same therapeutic effects of oral administration while utilizing half the dose. This method is also extensively used by people attempting to abuse certain psychoactive drugs._

Twice as much?! That big of difference?


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## metamorphosis (Dec 18, 2008)

Yeah, on each drug is metabolized, by which enzymes and other drugs being used. Also, if a person is enzyme deficient. For instance, it is a known fact that asenapine must be used sublingually to bypass the first level of metabolism to be effective. Other drugs like benzos and b-vits are also either quicker acting or more efficient. There are a various number of ways to administer drugs. Many are considered quicker and metabolically more potent. Think about it while you go get your B-12 shot!!!
Others are 97% as bio-available orally if ya wait!!!


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## WineKitty (Nov 26, 2004)

I take my Klonopin sublingually at times simply for lack of availability of water but I fail to notice any difference in how fast it works. It is absolutely no more potent.


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## metamorphosis (Dec 18, 2008)

WineKitty said:


> I take my Klonopin sublingually at times simply for lack of availability of water but I fail to notice any difference in how fast it works. It is absolutely no more potent.


Wrong, klonopin will hit you much faster sublingually. As long as you let it dissolve under the tongue and your not eating or drinking water. Been taking it long enough to know!


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## basuraeuropea (Jul 25, 2012)

metamorphosis said:


> Wrong, klonopin will hit you much faster sublingually. As long as you let it dissolve under the tongue and your not eating or drinking water. Been taking it long enough to know!


she may just hold a great tolerance to benzodiazepines and thus the difference between the two administration routes is so minimal so as to not pass the detection threshold.


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## istayhome (Apr 4, 2012)

A32 said:


> From wikipedia:
> 
> _However, many drugs are much more potent taken sublingually, and it is generally a safer alternative than administration via the nasal mucosa. Due to the high cost of pharmaceuticals, some people opt to split their pills and take them sublingually in order to obtain the same therapeutic effects of oral administration while utilizing half the dose. This method is also extensively used by people attempting to abuse certain psychoactive drugs._
> 
> Twice as much?! That big of difference?


I absolutely disagree. I have seen that this is the case for _some_ drugs, but not all drugs, I wouldn't even say most drugs. There is no physiological basis for this with most drugs and I don't think that wikipedia has the most reliable information.


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## riptide991 (Feb 1, 2012)

Sublingual can make some drugs weaker, like say, hmm codeine. Codeine is actually catalyzed in the liver by CYP2D6 into our favourite friend Morphine. So first pass can make a difference.


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## istayhome (Apr 4, 2012)

^good point smarty. I often wonder why codeine is even used as a pharmaceutical as the body does just turn it into morphine.


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## riptide991 (Feb 1, 2012)

I think it's just for the sake of potency/addiction. It's a small amount compared to say if you took straight morphine. It's such an addictive substance. I mean damn it feels good and you think to yourself, this is how I should feel.


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## istayhome (Apr 4, 2012)

kehcorpz said:


> I think it's just for the sake of potency/addiction. It's a small amount compared to say if you took straight morphine. It's such an addictive substance. I mean damn it feels good and you think to yourself, this is how I should feel.


Yeah I understand that, I just think prescribing an equianalgesic dose of morphine is a better idea. But as I did some reading on the subject I see that when these alkaloids are derived from poppy straw extract by the pharmaceutical industry (depending on the variety of poppy used) the codeine to morphine ratio is about 10:3 so I can see using codeine as a prodrug as opposed using it to synthesize other narcotics. Also of course codeine has less abuse potential.

I just always think that prodrugs are stupid. I mean why go through the middle man as opposed to just skipping to the real thing? That is a rhetorical question, just my thinking. Also, as with all drugs with abuse potential, doctors will always prescribe the "safest" but not necessarily the most effective drug. Too often people in serious pain are prescribed low dose codeine with tylenol as opposed to a drug that actually works. It's pretty frustrating to have family members in a lot of pain being denied effective analgesics but given codeine instead. But that all goes back to a topic which we discuss all to often Law and politics taking precedence over effective medical care.

You could say that I have a personal distaste for codeine. My Grandma recently died, she was hospitalized and in a lot of pain. She was on her way out. But even in her last days the Highly paid medical center she was in gave her all the tylenol 3 she wanted but denied her drugs that would have relieved her pain in her final days. When a person has a few weeks left to live, I say let them have all the good stuff they'd like. But you know, I never went to medical school.


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## UltraShy (Nov 8, 2003)

istayhome said:


> My Grandma recently died, she was hospitalized and in a lot of pain. She was on her way out. But even in her last days the Highly paid medical center she was in gave her all the tylenol 3 she wanted but denied her drugs that would have relieved her pain in her final days. When a person has a few weeks left to live, I say let them have all the good stuff they'd like. But you know, I never went to medical school.


Very sad story. Even more sad is how I'm not at all surprised by it, given that such crap is standard in our War on Drugs.

As my father laid dying in home hospice care his doc provided Vicodin. The man could barely swallow anything, yet he gets a pill that's gigantic to fit in 500 mg of Tylenol. He never used any of these monster pills. If he had, he'd likely have died by chocking to death instead.


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## istayhome (Apr 4, 2012)

Famous said:


> What about DHC codeine? I've had a low dose script for 7 years,
> when I had a tooth abcess I did try crunching and dissolving between cheek and gum, but didnt get any "extra" effect,


That's exactly what we're discussing. It is definitely not true that every drug is more potent when taken sublingually. I doubt it's even true of most drugs. You'll notice that A32 quoted wikipedia, hardly the most reliable source.


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## UltraShy (Nov 8, 2003)

metamorphosis said:


> For instance, it is a known fact that asenapine must be used sublingually to bypass the first level of metabolism to be effective.


That would be Saphris, the antipsychotic which I'm now using as a sleep aid.



metamorphosis said:


> Other drugs like benzos and b-vits are also either quicker acting or more efficient.


I've tried that with benzos a couple times, but the pills were never designed to melt under your tongue. Saphris dissolves very rapidly and is totally gone within a minute. Put a benzo under your tongue the same way and, well, I haven't timed it, but you're going to be waiting a damn long time. You end up with a pill that slowly turns to a chalky muck.

I'd love to see if sublingual benzo administration actually works better, as oral sure doesn't do much, but seems I'd need a formulation made for sublingual use.


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## riptide991 (Feb 1, 2012)

UltraShy said:


> That would be Saphris, the antipsychotic which I'm now using as a sleep aid.
> 
> I've tried that with benzos a couple times, but the pills were never designed to melt under your tongue. Saphris dissolves very rapidly and is totally gone within a minute. Put a benzo under your tongue the same way and, well, I haven't timed it, but you're going to be waiting a damn long time. You end up with a pill that slowly turns to a chalky muck.
> 
> I'd love to see if sublingual benzo administration actually works better, as oral sure doesn't do much, but seems I'd need a formulation made for sublingual use.


Umm rub it down till it melts.


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## yay (Dec 31, 2012)

That's gross. I almost threw up my sandwich.


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## GotAnxiety (Oct 14, 2011)

Sub ativan is way better then lorazeopam 2x+.


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## WineKitty (Nov 26, 2004)

metamorphosis said:


> Wrong, klonopin will hit you much faster sublingually. As long as you let it dissolve under the tongue and your not eating or drinking water. Been taking it long enough to know!


No, I am not wrong on how it affects me. I have been taking it long enough to know also (well over two years). I have never noticed any significant increase on when it "hits" me as the effect of a 1 mg pill that I take is subtle to me in first place. Certain generics are hard to dissolve more than others. I have no idea how a 2 mg pill would affect me though.

I have a tolerance to K-pin so I don't ever feel it "hit" me..it kind of just slowly has a calming effect. I take upwards to 3.5 mgs a day.

If it is faster it's not by much...10 to 15 minutes at most? :stu

If one wants a faster acting benzo, Xanax is much better for that. K-pins aren't known for being fast acting.


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## WineKitty (Nov 26, 2004)

I think there is something called a Klonopin Wafer that is designed for sublingual dissolving although I don't know much about it.


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## metamorphosis (Dec 18, 2008)

Klons. have a mild minty taste anyway. And it the regular Teva's will dissolve pretty quick. Leaving you not only relaxed and happy, but also, minty fresh!!!!


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## istayhome (Apr 4, 2012)

yeah there is a Klonopin wafer made to be taken sublingually so it has a much quicker onset. Otherwise the Benzo just dissolves and is eventually swallowed, effectively being taken orally.

In order for a drug to be taken sublingually t has to be water soluble and able to pass through the fine mucous membranes. Benzos don't fall into that category most drugs don't. And there is no medically scientific reason why taking a drug sublingually would double it's potency. 

Many drug abusers/misusers will snort any drug they get their hands on and they'll swear to you that the dug kicks in right away. This of course very bad for their health but also completely wrong. Crushing up and snorting a benzodiazapine is the epitome of stupid. The pill is all filler and the drug cannot be absorbed via the mucous membrane. Eventually the drug will take effect but only because it eventually drips down the esophagus and into the stomach, effectively being taken orally (except you waste some medication and destroy nose in the process.)


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## Skitzo (Feb 2, 2013)

I thought it just kicks in quicker


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## RelinquishedHell (Apr 10, 2012)

I've tried taking Klonopin sublingually and it made no difference, I always feel it kick in 2 hours after I take it.


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## Spungo (Jul 30, 2012)

A32 said:


> From wikipedia:
> 
> _However, many drugs are much more potent taken sublingually, and it is generally a safer alternative than administration via the nasal mucosa. Due to the high cost of pharmaceuticals, some people opt to split their pills and take them sublingually in order to obtain the same therapeutic effects of oral administration while utilizing half the dose. This method is also extensively used by people attempting to abuse certain psychoactive drugs._
> 
> Twice as much?! That big of difference?


Depends on the drug. Some drugs are strongly metabolized during First Pass Metabolism (Google that term). Bupropion is one of those drugs. If you take Bupropion under the tongue, you'll get a much stronger dopamine kick because passing through the liver turns it into more of an adrenergic drug. Taking an MAOI under the tongue has similar improved effects because MAO exists in the GI tract. Skipping the GI tract means more of the MAOI gets into your brain. SSRI drugs work much better sublingually because the GI tract also contains serotonin receptors. This is why drugs like venlafaxine and fluoxetine cause major diarrhea - they hit your GI serotonin receptors. Taking them under the tongue skips the GI tract, so it prevents diarrhea, and it has the added benefit of making the drug work better.


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## Skitzo (Feb 2, 2013)

yeah but thats just how klonopin is either way takes that long to reach peak level?


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## istayhome (Apr 4, 2012)

Spungo said:


> Depends on the drug. Some drugs are strongly metabolized during First Pass Metabolism (Google that term).* Bupropion is one of those drugs. If you take Bupropion under the tongue, you'll get a much stronger dopamine kick because passing through the liver turns it into more of an adrenergic drug.* Taking an MAOI under the tongue has similar improved effects because MAO exists in the GI tract. Skipping the GI tract means more of the MAOI gets into your brain. SSRI drugs work much better sublingually because the GI tract also contains serotonin receptors. This is why drugs like venlafaxine and fluoxetine cause major diarrhea - they hit your GI serotonin receptors. Taking them under the tongue skips the GI tract, so it prevents diarrhea, and it has the added benefit of making the drug work better.


Can you point me in the direction of any reference that supports this claim regarding Bupropion?

Also being well studied in Anatomy and Physiology, your talk of "first pass metabolism," is an all too commonly used term that is absolutely meaningless.


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## viper1431 (Jun 6, 2012)

Skitzo said:


> I thought it just kicks in quicker


That's what i thought and certainly seems the case with benzos. Just checked the manafacturers info and the only difference was rate of absorbtion. They even specically state

"Bioavailability was shown to be identical by all routes of administration "

Sublingually it still wasn't that fast, still looking at an hour or so for most benzos unti peak levels. It's not like injection form where it's in minutes.

For interests sake in the case of ativan (the last page i have open) the ingerdients between normal and sublingual tablets are the same except for 
Polacrilin Potassium which is used to help the normal tablet break up (replaced with corn starch in the sublingual tabet)


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## Spungo (Jul 30, 2012)

istayhome said:


> Can you point me in the direction of any reference that supports this claim regarding Bupropion?


http://www.cjem-online.ca/v12/n2/p158


> For bupropion insufflation to cause seizure, significantly elevated levels of bupropion in the cerebrospinal fluid (CSF) would be required. After oral administration, bupropion is rapidly absorbed and approximately 95% of the dose undergoes extensive first pass hepatic metabolism, primarily by cytochrome P450 2B6, before being distributed throughout the rest of the body.19 Nasal insufflation can be expected to deliver the drug to the body and CSF before circulating through the liver, thus bypassing its first pass metabolism and resulting in higher plasma concentrations. Consequently, ED physicians should examine the nares for powder in patients with unexplained seizure and delirium.


Basically it's referencing the stats saying the risk of seizures dramatically increases at high doses. If you're doing something like snorting it, you're pushing that seizure risk even higher because the drug reaches higher concentrations when it's taken in a way that skips the first pass.

Off topic,
It's also worth mentioning that several SSRI drugs use the same enzyme as bupropion, so bupropion and SSRI drugs have significant interactions with each other. Bupropion will give fluoxetine a harder kick, and fluoxetine gives bupropion a harder kick. On top of that, those drugs also inhibit their own metabolism. Bupropion turns into hydroxybupropion, and that metabolite uses the same enzymes as bupropion and fluoxetine, so the metabolites themselves increase the concentrations of bupropion and fluoxetine. Similarly, fluoxetine turns into norfluoxetine, and norfluoxetine blocks the enzyme that destroys fluoxetine and bupropion. Taking those two drugs together works great, and this is why some studies have concluded that taking bupropion with an SSRI is more effective than taking just one or the other.

http://www.ncbi.nlm.nih.gov/pubmed/3149241


> Bupropion exhibits extensive first-pass effect and is mainly cleared by hepatic route. In rats with hepatic damage, maximum plasma concentration (Cmax) was approximately 3 times higher and area under the plasma concentration-time curve up to 6 h (AUC 0-6) and AUC 0-infinity increased on an average 4 and 5 times respectively compared to the control. The half-life was doubled with hepatic dysfunction. These findings suggest that hepatic impairment in rats causes a decrease in first pass effect as well as an increase in the half-life of the drug. Rats with renal impairment, exhibited a significant increase in Cmax, AUC 0-6 and AUC 0-infinity of bupropion approximately 3-fold as compared to the control, no change in half life of the drug was observed. This indicates that rats with renal impairment show less efficient first-pass effect which may lead to increase in systemic bioavailability. The time to peak observed in all treated animals was not significantly different from the control. The percentage of bound bupropion did not differ either in CCl4 or gentamicin treated plasma as compared to the control.


This one is saying that first pass has a significant effect.

Wiki has a nice table showing the receptor affinities of bupropion and its main metabolites: hydroxybupropion and hydrobupropion.
http://en.wikipedia.org/wiki/Bupropion#Pharmacokinetics
Notice that bupropion has stronger affinity for dopamine transporters while hydroxybupropion and hydrobupropion have stronger affinity for noradrenaline transporters.


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## istayhome (Apr 4, 2012)

^^^ I understand all of that very well.

to define the all to commonly used phrase "first pass metabolism": This term refers to a drug being metabolized by it's given liver enzyme, at which point it is turned into it's metabolites.

So if one were to wait a very long time while a bupropion sr tab dissolves under their tongue and is slowly absorbed by the mucous membranes in the mouth then the bupropion should enter their bloodstream quicker than if it were taken orally.

At that point the drug does exactly what it would do had it been taken orally. It is circulated through the blood and metabolized by the liver into it's active metabolites.

So taking bupropion sublingually may lead to a quicker peak of action but that's about it. It is still going to be metabolized at the same speed as if taken orally. By taking it sublingually, it is simply _absorbed_ more quickly.

I highly doubt anyone can get a real dopamine "kick" from waiting for a tablet to dissolve under their tongue. I'll give it a try though the next time I want a nasty taste in my mouth for an hour while I make sure not to swallow.

I will also note that the metabolites of bupropion do have a very slightly stronger affinity for NE vs. DA, however that difference in affinities is so low as to be insignificant. 100% for bupropion compared to 106% for hydroxy-bupropion, affinities for NE uptake.
Bupropion and it's metabolites act much more strongly on DA than NE.


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## mrfreeze (Feb 5, 2013)

What's Bupropion? Is this strong?


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## Spungo (Jul 30, 2012)

istayhome said:


> I highly doubt anyone can get a real dopamine "kick" from waiting for a tablet to dissolve under their tongue. I'll give it a try though the next time I want a nasty taste in my mouth for an hour while I make sure not to swallow.


It seems to only work with the white wellbutrin pills. You need to bite it once to open the pill then let it sit under the tongue. Those ones had a definite kick, and it would numb my mouth. I did that while riding the bus, and I could barely swallow by the time I got to work.
The purple ones taste a million times worse and I haven't noticed any kick. They turn into this weird mush when sitting under the tongue. They cost less because they suck.

Maybe it's not a first pass effect. Maybe it's the same exact chemicals as swallowing it, but it all slams you at the same time? I like when drugs have a bit of a kick. If you take something like Dexedrine or ephedrine, it has this hard immediate feeling and you know it's doing something.


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## riptide991 (Feb 1, 2012)

Yes the drug will eventually end up at the liver but some of the drug will actually cross the blood brain barrier or be deposited in tissue and hence why it's called bypassing 1st pass. When going through the gut it actually gets absorbed through the portal system (A network of veins in hepatic region) and not general circulation. This system is there to protect you and it shuttles everything to the liver before allowing it to go to general circulation. You can bypass this by going through the nasal route, through your rectum, etc. It will go right into circulation. Plus the liver isn't really the only place that has CYP enzymes to break down to metabolites, they occur in the brain too.


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## viper1431 (Jun 6, 2012)

I've tried bupropion under the tongue, the only effect was the most foul taste you will ever come accross in your life. I don't know what they put in the tablets but it sure works to discourage you from wanting to taste it again.


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## WineKitty (Nov 26, 2004)

K-pins have that nice almost minty taste. I just got my 3 month supply of the Teva Generic and am thrilled. Was getting a crappy generic from the local pharm. Teva is the best generic clonazepam I have tried to date.


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