Question about Subutex for someone who really really really knows :)

[JessFR]

Well, here's my understanding.

Ok so, say you're a heroin addict. If you take it after 24 hours, much of the heroin in your system will have worn off, and you'll be in withdrawel. The buprenorphine will take effect resulting in a net increase in opioid activity in your system, making you feel better.

If however you don't wait the 24 hours, the buprenorphine will strip the heroin off your system and replace it with itself, since bup is a much weaker partial agonist as opposed to a strong full agonist like heroin, your system experiences a sudden and significant decrease in opioid activity.

I believe it's the sudden shock reduction in opioid activity that causes the preciptated withdrawel. If you wait the 24 hours, you'll have started to go into withdrawel but your body will have had time to adjust.

As you experience withdrawel, your body is adjusting and will eventually recover. At 24 hours you've had 24 hours for your system to adjust. With preciptated withdrawel, your body goes into a significant level of withdrawal almost immediately.

This is how it works to the best of my understanding, in terms of why it makes a difference and why how you feel is so different if you wait the 24 hours or not.

I hope I understood your question and I hope this helps understand the difference.

 

[Plumber101010]

Well, here's my understanding.

Ok so, say you're a heroin addict. If you take it after 24 hours, much of the heroin in your system will have worn off, and you'll be in withdrawel. The buprenorphine will take effect resulting in a net increase in opioid activity in your system, making you feel better.

If however you don't wait the 24 hours, the buprenorphine will strip the heroin off your system and replace it with itself, since bup is a much weaker partial agonist as opposed to a strong full agonist like heroin, your system experiences a sudden and significant decrease in opioid activity.

I believe it's the sudden shock reduction in opioid activity that causes the preciptated withdrawel. If you wait the 24 hours, you'll have started to go into withdrawel but your body will have had time to adjust.

As you experience withdrawel, your body is adjusting and will eventually recover. At 24 hours you've had 24 hours for your system to adjust. With preciptated withdrawel, your body goes into a significant level of withdrawal almost immediately.

This is how it works to the best of my understanding, in terms of why it makes a difference and why how you feel is so different if you wait the 24 hours or not.

I hope I understood your question and I hope this helps understand the difference.

Nope, you understood it perfectly and did a great job! I am starting to like this website, it has a large class of individuals with a higher intellect than most

That said, this is basically what the entire conversation is about and you were able to reduce it to much less words
than me LOL. I guess that's what I'm trying to get at. Because we are not just talking about going through a rough time, we're talking about people that are experiencing such horrible symptoms that some of them are being rushed to the emergency room!

There is a sudden shock, yes, but that shock is immediately replaced by another product thats sole purpose and design is to take AWAY withdrawal. In fact I would call it a miracle drug. That's why I find it so hard to swallow that this miracle drug once it kicks out whatever is in its way and fills a receptor, would STILL go on to cause an individual to be rushed to the emergency room.

So you are correct in your understanding and you are correct in your explaining, but what I'm looking for is the specific "WHY" sudden removal, if it's being replaced by a product that prevents the exact same thing it is now causing, is causing it? Because in my opinion it should not. And evidently there are others that didn't wait like myself and also didn't experience any issues whatsoever.

There's a world of difference in making someone go through 24 hours of detox prior to taking the pill, or just popping the pill in your mouth and walking out the door. Also, I just can't imagine 24 hours being that long enough of a time span, long enough to cross that threshold to prevent it.

Several days or a week makes sense. It's not like 24 hours later and your body has no signs of it. Most pills last for 4-8 hours anyway I just don't see 24 hours being enough to make such a difference that it would prevent people from being rushed to the emergency room with extremen withdrawal.

Worse, it's not like when you do your last Percocet you immediately start withdrawal to begin with. You could do your last pill and probably wouldn't even hit bad enough symptoms of withdrawal to mention for at least 8-12 hrs. So now what you're really talking about is only for 12 hours.

 

[Plumber101010]

Keep in mind this is all not just about curiosity. Its purpose is 2 fold. It's also about bringing into question a long tradition of practice of doing something that I don't believe needs to be done. If 99.9999 percent of everybody puts themselves through a 24 hour detox when in reality, only say 10 percent need to because of the chemical structure of their body, or for whatever reason, than 90 percent can successfully not have to worry about it!

So being able to prove that with an actual scientific reason, a medical reason, a specific finite reason as to WHY it can be done, can help me to achieve that. To bring to light something that has been done for such a long time, does NOT have to be done. And since nobody is doing it like that, it's really hard to prove otherwise.

Hopefully people will start writing in that they didn't do it and had no problems as one responder already did. Because at this particular point, I still FIRMLY believe that for the vast majority of people that are going on Subutex or Suboxone, a 24 hour detox is absolutely not needed.

 

[Pickledlemons]

I am glad you asked this question, because I have always wondered from the first time I took suboxone. Why does replacing a full agonist with a partial agonist produce a worse withdrawal than having a full agonist leave the receptor completely.
First time I took subs 24 hours as asked. Next time 18 hours next time 14 and so on until I was only waiting 2 hours. And it still worked - kind of. It at least didn't make the withdrawals any worse. I was almost convinced same as you. I even thought maybe I was a special case.

Then one time I tried taking it 10 minutes after taking fentanyl. It was the worst thing I have ever experienced in my life by far, and I have withdrawn from heroin, have died and spent 3 weeks in the hospital, been hit by van, drowned in a pool, tripped on mushrooms alone in a snowstorm with no way way home, precipitated withdrawal was worse than all of them combined and quadrupled. I was in a literal pool of sweat, no part of my body could stay still, my eyes were red and sore from crying for hours, I was hallucinating people and things, I stuttered and mumbled as I forced myself to speak one sentence to my girlfriend. I KNEW opiate withdrawal couldn't kill you but I still wondered if I would be alive by morning. You have a valid question, and you are probably right that 24 hours isnt necessary. but precipitated withdrawal is real, I promise you.

As for WHY - I still wonder myself, sorry.

 

[JessFR]

I think the big problem is bupe isnt replacing the heroin or whatever drug of choice in your system to the same extent.

If you're high on heroin and take bup, the bupe can't replace the level of opioid activity you were experiencing from heroin. So the net opioid activity in your system experiences a sudden drop..

Whereas at 24 hours you're already in withdrawel so the bup causes an increase in opiood activity making you feel better.

With all this said though, one thing ive consistently found with tolerance and withdrawel and such, is that it is very conplicated and sorting out a solid system of rules you can use to predict what will happen in various situations is extremely difficult.

I've tried for years and still find myself surprised.

But the best explanation I can give you is you is to say i believe its due to how your overall opioid activity in your system is affected (net increase at 24 hours, net decrease at 0 hours). And likely also influenced by the fact that at 24 hour's you've had 24 hours for your system to adjust to being in withdrawel.

From the moment withdrawel starts your body is trying to fix the chemical imbalance. And with a short acting drug like heroin or IR oxy 24 hours is a decent amount of time. It only takes a week or so for your system to mostly fix itself with a half life that short.

In a nutshell, if bup displaced the opioids on your receptors with itself and was itself a strong opioid agonist, i dont believe youd experience precipitated withdrawel. The problem is bupe isnt a strong agonist. Its not an antgonist like naloxone, but so long as its significantly less strong in its receptor interactions than the drug its displacing, your body will experience a sudden loss in opioid activity in your cells. And a sudden loss in opioid activity causes withdrawel.

A gradual drop in activity from the drugs wearing off causes regular withdrawel, but a sudden drop in activity will cause even worse withdrawel. Because your system has had no time to adjust to it.

 

[Plumber101010]

I am glad you asked this question, because I have always wondered from the first time I took suboxone. Why does replacing a full agonist with a partial agonist produce a worse withdrawal than having a full agonist leave the receptor completely.
First time I took subs 24 hours as asked. Next time 18 hours next time 14 and so on until I was only waiting 2 hours. And it still worked - kind of. It at least didn't make the withdrawals any worse. I was almost convinced same as you. I even thought maybe I was a special case.

Then one time I tried taking it 10 minutes after taking fentanyl. It was the worst thing I have ever experienced in my life by far, and I have withdrawn from heroin, have died and spent 3 weeks in the hospital, been hit by van, drowned in a pool, tripped on mushrooms alone in a snowstorm with no way way home, precipitated withdrawal was worse than all of them combined and quadrupled. I was in a literal pool of sweat, no part of my body could stay still, my eyes were red and sore from crying for hours, I was hallucinating people and things, I stuttered and mumbled as I forced myself to speak one sentence to my girlfriend. I KNEW opiate withdrawal couldn't kill you but I still wondered if I would be alive by morning. You have a valid question, and you are probably right that 24 hours isnt necessary. but precipitated withdrawal is real, I promise you.

As for WHY - I still wonder myself, sorry.

Wow!!! What a life you've had! Great stories Sad, but interesting what some people have gone through in their lives. So maybe it's just that also. It has to do with not only what levels are in you at the time, but also how powerful it is to begin with.

Fentanyl is some scary stuff and is making a lot of people rethink their habits. With your case I think it was about being such a short amount of time, only 10 minutes, combined with probably the most powerful drug in existence! 10 minutes wasn't even long enough to give the drug enough time to fully hit you and for all you know you could've actually saved your own life!!

Could have been you were going to overdose and die and taking it was meant to be because it was able to kick some of it away from you

I think we can all agree that 10 minutes is just pushing it, but going back to the many times you did it before your bad reaction, I think safe to say is another indication that the 24 hr detox was not needed and it worked successfully without it!

 

[Jekyl Anhydride]

There has been stories of people who have revived people who were borderline OD'ing with Subs but it's far from idyllic. An inverse agonist is best followed by an antagonist but IIRC Naltrexone takes longer to work than Naloxone. Especially with the intranasal dispensers.

With some of these Fent OD's it takes 6 shots to bring people back, freakin scary.

 

[Plumber101010]

I think the big problem is bupe isnt replacing the heroin or whatever drug of choice in your system to the same extent.

If you're high on heroin and take bup, the bupe can't replace the level of opioid activity you were experiencing from heroin. So the net opioid activity in your system experiences a sudden drop..

Whereas at 24 hours you're already in withdrawel so the bup causes an increase in opiood activity making you feel better.

With all this said though, one thing ive consistently found with tolerance and withdrawel and such, is that it is very conplicated and sorting out a solid system of rules you can use to predict what will happen in various situations is extremely difficult.

I've tried for years and still find myself surprised.

But the best explanation I can give you is you is to say i believe its due to how your overall opioid activity in your system is affected (net increase at 24 hours, net decrease at 0 hours). And likely also influenced by the fact that at 24 hour's you've had 24 hours for your system to adjust to being in withdrawel.

From the moment withdrawel starts your body is trying to fix the chemical imbalance. And with a short acting drug like heroin or IR oxy 24 hours is a decent amount of time. It only takes a week or so for your system to mostly fix itself with a half life that short.

In a nutshell, if bup displaced the opioids on your receptors with itself and was itself a strong opioid agonist, i dont believe youd experience precipitated withdrawel. The problem is bupe isnt a strong agonist. Its not an antgonist like naloxone, but so long as its significantly less strong in its receptor interactions than the drug its displacing, your body will experience a sudden loss in opioid activity in your cells. And a sudden loss in opioid activity causes withdrawel.

A gradual drop in activity from the drugs wearing off causes regular withdrawel, but a sudden drop in activity will cause even worse withdrawel. Because your system has had no time to adjust to it.

Well said! And very true it may well be a complicated combination of all things together. Individual body chemistry, combined with levels in the system combined with what type drugs in the system. One of the problems with me pushing that it's not needed is who knows what person may follow that advice and wind up in the emergency room? Doesn't matter if they are in the minority, try explaining that to them after they walked through hell! Which may very well be why they just tell everybody to go 24 hours and than they won't have to worry about such things

Still, it is a very convenient amount of time, in a matter of time as not all drugs disappear in 24 hours that's for sure. And yes I do know that some saynit could take 36 hours but that is rare. I've never actually experienced that firsthand I just hear some people say the 36 hour thing. In all of my experiences, the docs said to wait 24 hours later and come back tomorrow to do your first pill.

Now that I am now a pro at all of this, my system is really simple. She does the last pill at night time and then goes to sleep, when she wakes up which is normally about 12 hours later, she does her first Sub and as such has never had a bad reaction and has always has at least 8 to 12 hours under her belt. I don't do that because I think something bad will happen, as much as why bother because everyone has to go to sleep anyway LOL

 

[Plumber101010]

There has been stories of people who have revived people who were borderline OD'ing with Subs but it's far from idyllic. An inverse agonist is best followed by an antagonist but IIRC Naltrexone takes longer to work than Naloxone. Especially with the intranasal dispensers.

With some of these Fent OD's it takes 6 shots to bring people back, freakin scary.

Very intriguing actually. Because in theory if you were to take Suboxone that has Naloxone in it and not Subutex, there isn't much difference other than processing time. I keep four of the Narcan nasal spray's handy at all times and in a pinch I could see where that would actually work. Again, other than the fact that if respiratory depression hits, you don't have an awful amount of time before they die and it may take the pill longer to dissolve and hit than is worth doing.

Guess you could keep one crushed up and ready to inhale??!

 

[JessFR]

One phamacological question ive never gotten a satisfactory answer to is what the point is of adding naloxone to buprenorphine like with subuxone.

Unless im mistaken, buprenorphines binding affinity is still even stronger than naloxones. So naloxone shouldnt be effective against buprenorphine.

 

[Jekyl Anhydride]

One phamacological question ive never gotten a satisfactory answer to is what the point is of adding naloxone to buprenorphine like with subuxone.

Unless im mistaken, buprenorphines binding affinity is still even stronger than naloxones. So naloxone shouldnt be effective against buprenorphine.

It more of a marketing ploy to give it a CSA schedule 3 rating so it could be doled out much easier vs schedule2 which requires more clearance and fussing. A short course and doctors could be Addiction Specialists and rake in more $.

 

[Plumber101010]

I had a physician who's specialty is addiction respond over at the other website where I posted that question and it looks like he has pretty much agreed with my prior summation about it just be a combination of the persons make up, as well as the type drug as well as other factors. I post here now for all to read:

The person with the opioid dependency will respond the way their system uniquely responds. Their metabolism of say "oxycodone" may well be faster or slower than another persons. So, genetic makeup of an individual will have an effect on their response when buprenorphine is induced. Oxycodone will occupy 100% of the opioidreceptors. Buprenorphine will occupy between 70- 90 % of the receptors. An analogy could be you are driving a car at 100 MPH and you suddenly slow the car to 75 MPH. So no the response is not horrible but is noticeable. It also has to do with how many times a given person has gone through withdrawal and what dosage of opiates a person has been taking. If it is someones first time and they are a heavy user of say Methadone at 180 mg daily for 4 yrs, they are going to have a nasty, nasty withdrawal. If it is someone that has been on 60 mg of Hydrocodone for 6 months, the withdrawal is going to be less severe. So if you look at this in the context that patient information is generally given to advise people of worse case scenarios. I always advise patients that the longer they have been off, the less likely that any withdrawal will occur. You do make a very good & valid point. Everyone is going to be a little bit different in their experience. Hope this helps!

 

[JessFR]

It more of a marketing ploy to give it a CSA schedule 3 rating so it could be doled out much easier vs schedule2 which requires more clearance and fussing. A short course and doctors could be Addiction Specialists and rake in more $.

Which again makes me ask. Is there ANY pharmacological justification? Or is it all bullshit.

 

[Jekyl Anhydride]

I think it helped Suboxone sail through the approval process with the FDA as having Naloxone made it appear to be bullet proof regarding abuse but they didn't get overly picky about the Ki / binding affinities. Most everything else with Naloxone/ Naltrexone like Embedda is scary as hell to try an abuse.

 

[Keif' Richards]

Which again makes me ask. Is there ANY pharmacological justification? Or is it all bullshit.

There is no pharmacological benefit to pairing the Buprenorphine with Naloxone. Suboxone was a majorly successful example of to what you might refer to as pharmaceutical evergreening, although that's a bit of a misnomer, as Buprenorphine existed previously, but never actually received truly extensive use prior to its introduction as an addiction maintenance medication.

Pairing Buprenorphine with Naloxone allowed Reckitt Benkiser to maintain legal control of a patent which in all good conscience, should have died, allowing proliferation of low-cost Buprenorphine to whomever may have needed it. It's not a conspiracy theory, unless your grasp of human greed is really that naive. The "market" (Heroin Addiction) was exploding right as the above stated holding's Buprenorphine patent was expiring. So, they pair Buprenorphine with Naloxone and sell it as a new and improved version, but not only improved, the "old" version was now in fact, inferior.

The Naloxone in Buprenorphine has essentially zero clinical effect. This is especially so when the medication is taken by any route other than Sublingually. Even if taken intravenously, there's no hard and fast evidence that it has any modulating effect whatsoever. In fact, it's believed that the Naloxone in Buprenorphine frequently is what leads to a given patients' intolerance to the side-effects of Suboxone, but Subutex is generally not available to the general public in the United States without a reason. Not to mention, folks sell "White Bupe" (Subutex) in my area at a 400% premium in the belief that it will not cause precipitated withdrawal due to the absence of Naloxone.

Life lesson: Everyone, who says anything at the Methadone clinic ever, is wrong. Taking even the most seemingly benign advice seriously from folks at the clinic can easily lead to permanent injury, disability and/or death.

 

[Pickledlemons]

haha! he's right! After that really bad precipitated withdrawal I had... sweating, tears, RTL, all the usual effects and more my friend asked at the clinic and they told her I was ODing and next time that happens i need naloxone. I was pretty upset. Its these peoples jobs to provide this information and if they had intervened they probably would have made it worse. At least not helped. Unbelievable. ODed? on my daily dose of suboxone? I was conscious. PAINFULLY CONSCIOUS! And they want to give me a drug to revive me? Even if it had no affect like you say, even an ativan would help more than narcan.

 

[Keif' Richards]

The lack of knowledge possessed by certain doctors regarding pharmacology is astounding. Unless you trust your prescriber in the same way you trust your grandmother to send you a check for $13.50 for your birthday each year, you need to be conducting your own research and making your own, informed determinations regarding these drugs. One could say that (of course, among other contributing factors) the Opioid epidemic's patient-zero if you will, was a Medical Doctor who was told by a salesman from Purdue Pharma that although, Oxycodone, a well-known, highly-potent, potentially more-addictive Opioid substance than Heroin itself, that has been in clinical use for literally a century, was somehow utterly benign when formulated as a timed-release product and the doctor "took the dude's word for it".

They're all criminals in my opinion. Just like Bankers. Just like Hedgefund managers. The medical establishment (excluding nurses) is filled with greedy, self-serving borderline-malevolent individuals and somehow, genuinely honest and caring people seem to find their way in from time to time.

 

[JessFR]

There is no pharmacological benefit to pairing the Buprenorphine with Naloxone. Suboxone was a majorly successful example of to what you might refer to as pharmaceutical evergreening, although that's a bit of a misnomer, as Buprenorphine existed previously, but never actually received truly extensive use prior to its introduction as an addiction maintenance medication.

Pairing Buprenorphine with Naloxone allowed Reckitt Benkiser to maintain legal control of a patent which in all good conscience, should have died, allowing proliferation of low-cost Buprenorphine to whomever may have needed it. It's not a conspiracy theory, unless your grasp of human greed is really that naive. The "market" (Heroin Addiction) was exploding right as the above stated holding's Buprenorphine patent was expiring. So, they pair Buprenorphine with Naloxone and sell it as a new and improved version, but not only improved, the "old" version was now in fact, inferior.

The Naloxone in Buprenorphine has essentially zero clinical effect. This is especially so when the medication is taken by any route other than Sublingually. Even if taken intravenously, there's no hard and fast evidence that it has any modulating effect whatsoever. In fact, it's believed that the Naloxone in Buprenorphine frequently is what leads to a given patients' intolerance to the side-effects of Suboxone, but Subutex is generally not available to the general public in the United States without a reason. Not to mention, folks sell "White Bupe" (Subutex) in my area at a 400% premium in the belief that it will not cause precipitated withdrawal due to the absence of Naloxone.

Life lesson: Everyone, who says anything at the Methadone clinic ever, is wrong. Taking even the most seemingly benign advice seriously from folks at the clinic can easily lead to permanent injury, disability and/or death.

I'm pretty much the world's biggest conspiracy theory skeptic, but that sounds highly likely to me. But then it's pretty close to what I already assumed.

But it was one of those things that just seemed so blatant and obvious to me (that the naloxone in has no pharmacological justification) that it was hard to believe.

I'm not sure why though, the pharmaceutical industry does shit that has no pharmacological value purely for marketing or patent purposes all the time.

Like I said, I'm a big anticonspiracy theorist, I don't believe in "evil poison peddling big pharma". But I do believe in the big pharma that's dishonest and misleading in advertising like almost every successful company is.

It is disappointing how little chemistry and pharmacology most people, let alone most doctors possess.

 

[Plumber101010]

Almost every single pharmaceutical company, come time their patent starts to run out, tries some kind of a trick or a tweak or a twist to keep their product line going. At least in this case they actually, literally added something new to it. Useless agreed but at least they actually did something different. I'm NOT saying to give them any credit, because it's a bunch of fake crap, ALL OF IT, but at least they were a little bit more forward with it.

I've known other pill companies that changed very little (if anything) to their pill and make up but rebranded it to be "New and Improved" when it was basically the exact same thing. And as was just said, worse, will tell you the old product they just successfully touted for 20 years wasnt any good anymore..

But don't limit the craziness to just pharmaceutical companies. The world at large is turning in to a crap place. Big corporate dog eat small dog world. Almost ALL companies are looking to take advantage of ALL people. I'm one of these fighters for the righteous and I see stories every single day that just infuriates me. Big-name companies in tools, electronics, auto parts, ALL branding things and labeling things that are more or less LIES to the General Public, born and based upon the general publics own ignorance to see any further than the label they read promoting that own companies product!

It's sad, it's very very sad. And I don't see it ever getting better. Greed and profit and bottom line will always take precedence over anything else. And that my friends is the real life lesson. If there's money involved, you can pretty much not trust anybody concerning anything anymore.

Even in this case we have what I would still call a miracle drug. A drug that few can dispute will actually help cure the opiate epidemic. And than in all of their wisdom what do they do? They limit the amount of product that they will put out, limit the amount of doctors that can put it out, limit that same doctor to the amount of patients that he can see and then these doctors charge outrageous fees for office visits, require multiple office visits per month, for one reason and one reason only! People are desperate to become drug-free and the doctors know they are now LEGAL drug dealers.

Hey everyone, we have a CURE that can help wipe out OPIOID addiction worldwide. But HEY, let's not make that cure readily available to all the people who actually need it. Let's not give it out like candy on street corners because our only concern is having a drug free America. No no no. Let's regulate the piss out of it and make it harder to find than a one pound 24k nugget while panning for gold in Hawaii!

 

[Kittycat5]

Naloxone, even in minute doses can help curb OIC although Im quite positive that wasnt R&Bs reasoning. As said, its mostly garbage but it may deter the IV route of administration to some as well.