Opioids Confused about different ROA's and the drastic difference in Duration of Effect

[romealone]

I will admit to feeling dumb asking this as I am halfway throu medical school and feel I should know the answer..but it evades me for some reason.

I don't understand why different routes of administration (with the exception of oral) effect the duration of action of the drug soooo drastically.

Let's take bupe for example. It is accepted as fact that snorting bupe will give u a much shorter duration than sublingual. But why? They both utilize mucous membranes to get the drug into the bloodstream and both bypass first pass metabolism. So they should be roughly the same. Sure, some mucous membranes might have more surface area or be a bit more permeable so maybe the drug would kick in a bit quicker and thus last a bit shorter, but the difference should be almost negligible.

We can even extend this to IV vs sublingual. IV is obviously going to kick in immediately while sublingual maybe takes up to 30 minutes to enter the bloodstream, but beyond that, it seems the pharmacoKinetics should be the same. You either bypass first pass metabolism or you don't, there is no in between, and yet almost all agree that IV bupe has a relatively short duration while sublingual can last a full day or more.

Confused and embarrassed medical student.

 

[Crashing]

It's because the persons perspective of the high is relative to how quickly and intensly the high comes on. So while it may be effecting them technically the same amount of time, their experience feels shorter with IV/insufflation ROAs. Consider what a graph of a drug's effects on the users perception IV versus sublingually would look like. If the drug comes on immediately, then the feeling of coming down follows soon after, whereas if the drug takes longer than >1min there is a plateau effect experienced and therefore the effects seems to last longer.

Edit: Pure speculation ^

 

[pasha]

If you can find data on the pharmacokinetics of each ROA of each drug which is practically impossible, I'm sure you'll find contrasts in the duration of action which agree with your hypothesis.

Until then, you can only make inferences as to why.

 

[THC_LSD_OC]

Its pretty simple, really. The sublingual ROA will almost always vary in duration of effects vs IV + vs intranasal.
First of all, if you are using IV then you must have crushed the tablet + broken time release PLUS the IV route ensures that your body receives the full dosage immediately all at the same time.
Same concept with intranasal, as you must break the time release formula in order to snort the pill. And the drug will be entering your system at the same time and you will receive the full dosage.
With sublingual ROA, generally the formulas are time released already and your body will only break down a certain mg of the drug at a time. In other words, if you IV 30mg oxycodone (same w/ intranasal but nasal bioavailability is less), you will get the full 30mg dosage.
If you were to ingest 30mg oxy sublingual, your body would receive the full 30mg but it would not be delivered immediaately and it builds up instead of being released all at once, extending the half life.

 

[Mass08]

I disagree with you Crashing. It certainly isn't just a perception of the high that is different. When I use suboxone to detox from heroin with I notice that if I take some suboxone sublingual I can get 2 days of relief from withdrawals. If I snort it or IV it which I never do but have before, I am lucky if I get a full day of relief from withdrawals. I will feel the withdrawals kicking in noticeably quicker using those ROA's. I believe it is because IV and nasal reach peak plasma levels faster than sublingual dose therefore your body starts breaking down the drug quicker.

 

[romealone]

Im not talking about time released pills. In fact I specifically used bupe as an example which has no time release.

Its pretty simple, really. The sublingual ROA will almost always vary in duration of effects vs IV + vs intranasal.
First of all, if you are using IV then you must have crushed the tablet + broken time release PLUS the IV route ensures that your body receives the full dosage immediately all at the same time.
Same concept with intranasal, as you must break the time release formula in order to snort the pill. And the drug will be entering your system at the same time and you will receive the full dosage.
With sublingual ROA, generally the formulas are time released already and your body will only break down a certain mg of the drug at a time. In other words, if you IV 30mg oxycodone (same w/ intranasal but nasal bioavailability is less), you will get the full 30mg dosage.
If you were to ingest 30mg oxy sublingual, your body would receive the full 30mg but it would not be delivered immediaately and it builds up instead of being released all at once, extending the half life.

 

[Toz]

I always found that IV buprenorphine lasted just as long as any other ROA. Well, give or take one hour (the onset if taken any other way).

 

[Swimmingdancer]

It's because the persons perspective of the high is relative to how quickly and intensly the high comes on. So while it may be effecting them technically the same amount of time, their experience feels shorter with IV/insufflation ROAs. Consider what a graph of a drug's effects on the users perception IV versus sublingually would look like. If the drug comes on immediately, then the feeling of coming down follows soon after, whereas if the drug takes longer than >1min there is a plateau effect experienced and therefore the effects seems to last longer.

Edit: Pure speculation ^

Its pretty simple, really. The sublingual ROA will almost always vary in duration of effects vs IV + vs intranasal.
First of all, if you are using IV then you must have crushed the tablet + broken time release PLUS the IV route ensures that your body receives the full dosage immediately all at the same time.
Same concept with intranasal, as you must break the time release formula in order to snort the pill. And the drug will be entering your system at the same time and you will receive the full dosage.
With sublingual ROA, generally the formulas are time released already and your body will only break down a certain mg of the drug at a time. In other words, if you IV 30mg oxycodone (same w/ intranasal but nasal bioavailability is less), you will get the full 30mg dosage.
If you were to ingest 30mg oxy sublingual, your body would receive the full 30mg but it would not be delivered immediaately and it builds up instead of being released all at once, extending the half life.

Neither of these are correct. I wish people wouldn't respond just to make wild guesses

As Toucan said:

A lot of what you may experience as the main effects of the drug is where the drug is at peak concentrations, which will happen within a smaller time frame with a fast ROA.

Assuming one took equi-effective doses (as opposed to just equal quantities mg per mg), a ROA that causes the drug to be fully absorbed faster, reach the bloodstream faster and reach peak levels faster and more dramatically will generally also be eliminated to below the levels necessary to perceive effects sooner.

Of course it's a little more complicated than that and the specifics are going to vary depending on the drug and its properties. Here is info explaining the differences between IV and sublingual buprenorphine: Human Pharmacokinetics of Intravenous, Sublingual, and Buccal Buprenorphine.

I'm not sure if there is any similar study on nasal vs sublingual administration though. I have some thoughts about the differences but no more time to type at the moment. One question is: is it actually widely agreed that intranasal administration substantially shortens the duration?

 

[Crashing]

I disagree with you Crashing. It certainly isn't just a perception of the high that is different. When I use suboxone to detox from heroin with I notice that if I take some suboxone sublingual I can get 2 days of relief from withdrawals. If I snort it or IV it which I never do but have before, I am lucky if I get a full day of relief from withdrawals. I will feel the withdrawals kicking in noticeably quicker using those ROA's. I believe it is because IV and nasal reach peak plasma levels faster than sublingual dose therefore your body starts breaking down the drug quicker.

This doesn't even attempt to discount my theory.

He said: "IV is obviously going to kick in immediately while sublingual maybe takes up to 30 minutes to enter the bloodstream, but beyond that, it seems the pharmacoKinetics should be the same."

If you bypass first pass metabolism, then the action of the drug should be the same duration and only the onset should be different by a number of minutes, yet experience reports show that the difference in duration is as big as multiple hours and sometimes days.

Which I would agree, the pharmokinetics should be the same thus leading me to my theory.

Im imagining the pharmokinetics like a bottle with a small hole in the bottom. now, you could funnel 20oz of water through the top and it will slowly trickle out the bottom until its all gone, or you could take a 20oz bottle and pierce a hole in the bottom and it will still slowly trickle out, just because one is completely full and one is pouring in more slowly, the end result seems like the bottle would empty at the same time. IF that makes any sense.

So a bigger difference would be perceived with the bottle already full than with the bottle that is gaining the water throughout time, yet the same amount of water will pass through at the same amount of time, there is just different peak levels of water at different times so a bigger difference is perceived with one.

Duration of the high is perceptual, as your receptors could have tons of heroin in them yet you can still feel extremely sick, although your body still has a ton of dope in it so technically you should be feeling high, but since you are used to the rush of shooting it your perception is adjusted as such.\

Another example for my thinking as that a person who uses a gram of Heroin a day stops cold turkey, and on the second day feels ridiculously sick. Now, if the amount of morphine in their receptors was present at that time in an opiate naive user, that person would feel incredibly high. The reason the user doesn't feel that high although being full of heroin is due to his relative perception of the usual effects curve.

 

[regfairfield]

most opiates have a silly high oral b/a ... if you want to abuse it then sure snort plug inject w.e your pleasure. ive kept my tolerance at 30 mg since i was 22 ( 26 now ) by not doing it all the time and dosing orally...im not all about the "rush"..i would rather feel good for 3 hours than really good for 1...just me...

tldr oral ftw

 

[Swimmingdancer]

Duration of the high is perceptual, as your receptors could have tons of heroin in them yet you can still feel extremely sick, although your body still has a ton of dope in it so technically you should be feeling high, but since you are used to the rush of shooting it your perception is adjusted as such.\

Another example for my thinking as that a person who uses a gram of Heroin a day stops cold turkey, and on the second day feels ridiculously sick. Now, if the amount of morphine in their receptors was present at that time in an opiate naive user, that person would feel incredibly high. The reason the user doesn't feel that high although being full of heroin is due to his relative perception of the usual effects curve.

That is because of tolerance, which is due (in part at least) to real physiological changes and not simply getting subjectively used to the high. If an opiate-naive person uses a drug orally and a drug IV they are still going to have much shorter effects from IV so I don't see how the part I quoted has anything to do with your theory.