Opioids Fentanyl post Suboxone

[ThePharmacist25]

If someone was to take 2mg of Suboxone at 10 a.m. and then start sucking on a patch around 2 p.m. would the Naloxone block the effects of the patch? After about an hour with the patch via buccal administered, it was removed due to lacking effects.. About how long should one wait for readministering? It is a 50ug/hr Mylan patch. Thanks

 

[Captain.Heroin]

No, the naloxone won't block anything, ever, in Suboxone.

Will the buprenorphine still block the fentanyl? No, it won't. I had IV fentanyl after buprenorphine once, it worked just fine.

 

[StaffWriter]

Even without IV administration, fent will break through your sub dose. I'm on 2mg daily and whenever I get a fent patch (usually 75's), I'll cut it into three squares and use buccally. The first dose may not be quite as strong, but the longer you're off the sub, the better the fent will feel.

Edit: Sometimes it takes up to 45min to an hour for buccal admin of fent to work so be patient!

 

[bufoman]

The ability of bupenorphine to attenuate the subjective effects of a full opioid agonist like fentynal or hydromorphone has to do with the dose of bupenorphine one is taking. As other have stated many times, the nalaxone in suboxone is not significantly orally/sublingually active to be significant it is the bupenorphine which by acting as a high affinity partial agonist blocks or reduces the effects of the full agonists.

Studies have been done on the ability of bupenorphine to attenuate full agonist opioid subjective effects. Here are some of the results that may be of interest:

Bickel et al. 1988 found that 2 mg of bupenorphine failed to completely attenuate 6-18 mg of hydromorphone. Significant physical effects (pupil dilation) still occured and significant subjective opioid effects were reported. Subjects were treated with bupenorphine for 10-14 days before the hydromorphone challenge. Hydromorphone challenge was given 24 hours after last bupenorphine dose.

I have found that one can take full agonists if on doses of 3 mg of bupenorphine or lower per day. I am prescribed analgesics for my back pain and have switched between many of these drugs. It seems best to wait a few hours after the bupenorphine dose but one could probably take it immediatly although a higher dose would probably be required. 6-8 hours has been found to be plenty enough time. Of course the activity of the full agonist is still somewhat attenuated with 2 mg bupenorphine but not as much as one may think. Maybe 30% attenuation as a safe bet.

Higher doses of bupenorphine 8-16mg completely attenuate the effects of full agonists as the study reports and many bupenorphine users will attest too including myself. Some studies show this attenuation can last up to 72 hours following the last dose of bupenorphine [Rosen et al. 1993]. I believe I've seen a study that was able to overcome higher dose bupenorphine with a very high dose of a full agonist but am not sure on the specifics and don't have time to look now.

See:
Bickel et al. 1988. Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans.
http://jpet.aspetjournals.org/content/247/1/47.short

Rosen et al. 1993. Buprenorphine: duration of blockade of effects of intramuscular hydromorphone
http://www.sciencedirect.com/science/article/pii/037687169490121X

 

[dankstersauce]

^lol.

I want to take the hydromorphone challenge!

 

[comatoserct]

that's interesting about the hydromorphone. I was always under the impression that buprenorphine had a higher binding affinity than hydromorphone.

the fentanyl would make sense, as it is more potent, but hydromorphone is noticeably less potent than buprenorphine.

I mean, I take 1mg of suboxone a day and can shoot heroin 8-10 hours later and get high, so I don't think hydromorphone is the same as fentanyl in this situation. I guess it was just the chosen drug for the study.

 

[bufoman]

that's interesting about the hydromorphone. I was always under the impression that buprenorphine had a higher binding affinity than hydromorphone.

the fentanyl would make sense, as it is more potent, but hydromorphone is noticeably less potent than buprenorphine.

I mean, I take 1mg of suboxone a day and can shoot heroin 8-10 hours later and get high, so I don't think hydromorphone is the same as fentanyl in this situation. I guess it was just the chosen drug for the study.

The study is saying you can get near full opioid effects from hydromorphone while on low dose bupenorphine. This will occur with any full agonist like oxycodone, heroin, morphine, hydrocodone even low potency compounds like codeine. It is not a function of the Kd (affinity) but rather has to do with the fact that the bupenorphine is not fully occupying the mu receptors (fractional occupancy) and thus the partial agonist effect can be overcome by a full agonist if the right dose is given. This is because many cells have spare receptors and if a high enough dose is taken the full agonist can overcome competitive antagonism and partial agonists. Also if the dose is significantly high, the full agonist will give greater competition for binding and can help displace the bupenorphine by out competing it. For these reasons the dose response curve just shifts to the right until the dose of antagonist or partial agonist is near Bmax (full occupancy) than the max response decreases to zero for the competitive reversible antagonist or to the partial agonists intrinsic activity. This is especially true with antagonists and partial agonists with slower off kinetics than agonists which is common.

A full dose of bupenorphine will occupy a high portion of the mu opioid receptors whereas the lower doses will not. In the latter case enough mu receptors and associated G proteins can be stimulated by the full agonist to induce effects (spare receptor concept). With the higher doses the bupenorphine will overwelm the receptors (full occupancy) and near complete inhibition will occur.

Bupenorphine has a slow in vitro and in vivo association dissociation rate constants (k on and K off). Fentynal and many full agonists have more rapid on off kinetics. Fentynal is especially rapid. This means that if both drugs are present at their Kd concentrations (or at least equivalent occupancy levels) bupenorphine is going to occupy the receptors for longer durations than fentynal. This may affect the intrinsic activity that can be achieved but it depends as is a bit more complicated. At a level with no spare receptors (full occupancy) the effect of the full agonist will decrease to near zero. As the stimulation comes from bupenorphine. Thus the effect of the partial agonist wins out.

Thus the receptors fail to recieve enough full agonist stimulation. Due to bupenorphines lower intrinsic activity one will experience less of an effect and the fentynal effect will be effectively blocked. This is the same effect of a low dose of an antagonist even if the antagonist has higher affinity the dose and receptor occupancy will determine the degree of attenuation. If enough bupenorphine is taken to occupy all of the binding sites it will still significantly attenuate even high doses of fentynal. I know of people on 16 mg a day who could not get effects from 2 mg fentynal.

So as stated the specific effect has to do with the dosages and the resulting degree of receptor occupancy which is a function of the Kd and bmax and thus the plasma concentrations of the competing drugs, spare receptors and the level of receptor occupancy. At equivalent occupancy concentrations the drug with the slower off kinetics will overwelm the effects thus the activity of the full agonist will decrease (dose response curve is shifted to the right). This effect can be overcome until full occupancy than the partial agonists and antagonists will typically block the effects of the full agonists.

Also do not confuse potency with affinity. Although many times related pharmacokinetic and pharmacodynamic properties can effect this relationship.

See: Yassen et al. 2006. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of the Respiratory-Depressant Effect of Buprenorphine and Fentanyl in Rats

http://jpet.aspetjournals.org/content/319/2/682.full

 

[snooter420]

the bute will be binded so tightly to your opiate receptors youre not gonna fell any other opiate until the subs r plum out of your system.

 

[LuvH8Relationship]

the bute will be binded so tightly to your opiate receptors youre not gonna fell any other opiate until the subs r plum out of your system.

Not true. I have IVd an 8mg dilly 2 hours after 4mg of bupe. Didn't feel quite as strong but i was still very f*cking loaded.

 

[sub_tommy]

I know this post is kind of old. But I thought I would throw in my experience. I just recently had a very painful hernia removal surgery. I am taking 24mg of Suboxone daily and have been for 2+ years. I was told by my anesthesiologist that the only pain relief I could be given while taking Suboxone would be to take Fentanyl. The only catch was I would have to take it at the hospital. They could not prescribe me Fentanyl to take at home with Suboxone. I asked the Anesthesiologist would the Fentanyl really work while taking 24mg of Suboxone. He told me the Suboxone will not block Fentanyl. I never did take the pain meds, I just toughed it out. But too this day I'm still wondering if I could just take a 100mg patch of Fentanyl while still taking my 24mg's of Suboxone? Doesn't seem like anyone really knows for sure. Maybe I'll try today and report back.

 

[RTrain]

I know this post is kind of old. But I thought I would throw in my experience. I just recently had a very painful hernia removal surgery. I am taking 24mg of Suboxone daily and have been for 2+ years. I was told by my anesthesiologist that the only pain relief I could be given while taking Suboxone would be to take Fentanyl. The only catch was I would have to take it at the hospital. They could not prescribe me Fentanyl to take at home with Suboxone. I asked the Anesthesiologist would the Fentanyl really work while taking 24mg of Suboxone. He told me the Suboxone will not block Fentanyl. I never did take the pain meds, I just toughed it out. But too this day I'm still wondering if I could just take a 100mg patch of Fentanyl while still taking my 24mg's of Suboxone? Doesn't seem like anyone really knows for sure. Maybe I'll try today and report back.

Well this old ass thread was bumped about 2 years ago so I'll bump it again. I find it very odd that the only pain relief you'd be offered is short acting fentanyl at the hospital. There is no way they could give you much pain relief once you leave the hospital without taking a patch or pop home. And I do not think it would break through 24 mg a day, the amount of Bupe built up in your system from a dose that high is ridiculous. You might feel the effects of IV'd fentanyl for short period of time, and that'd probably require a dose that a hospital would never take the risk of administering.

That's just really an odd answer from the Dr. in regards to giving you pain relief. He may have not intended to give you anything to take home because of your history of addiction (I assume, you are on a huge dose of Suboxone), but would try to humor you with a shot of fentanyl that might break through the dose enough to feel it a bit, then send on your way and it'd wear off by the time you went home. Probably smart not to take it, would've cost you some ridiculous amount of money to take that offer....well idk why I am even writing like this guy might read a post he wrote over 2 years ago and it was the only post he ever made 8(