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  • BDD Moderators: Keif’ Richards | negrogesic

dihydrocodeine potinators

P

phsycra

Bluelighter
Joined
Feb 26, 2012
Messages
127
Hi

I live in the UK and wanted to know what types of otc antihistamines would be good at increasing the opiate effects. I have access to benzo xanny and vals wud it be best to use them instead?


Thanks
 
dihydrocodeine ive heard is just shit compared to codeine , but use doxylamine (Restavit in aus , not sure in UK) or maybe promethazine , which will sedate u abit more . ive heard recently mylanta is really good . definetly use the xanax or valium , they synergise great with codeine/(probably dihydrocodeine) , personally i would take .5mg xanax , 10mg valium (i have no benzo tolerance) , 30mg DXM 45-60 mins beforehand , 25mg restavit 30 mins before , then smoke weed about 15 mins after i dose 600mg codeine , that would be my ideal concoction lol . it is dangerous to mix benzos and opiates ..
 
Thanks for the reply. I'm looking for sumin to use in the day so the less sedating the better . Cheers mate
 
I don't see how mylanta could potentiate opioids... it sounds like someone found out about cimetidine (another antacid) being a good potentiator and assumed other antacids are and spread bullshit.

I could be wrong but don't know of any mechanism that would cause aluminum, magnesium and simethicone to potentiate opioids. In some guide to using opioids it was printed like a decade ago that naproxen can make opioids stronger (meaning it could increase the analgesia) and I see threads now and then claiming it's a potentiator as well when it doesn't synergize OR increase the effects via enzyme inhibition/induction.

OP, your best bet is to look at the opioid potentiation mega threads accessible at the top of this page in the Other Drugs directory.

ETA:

How exactly do you expect to make a sedating drug stronger without increasing the sedation?
 
Phsycra, there are essentially two types of potentiation, as Cane mentioned - inhibiting/inducing enzymes responsible for the metabolism of the opioid, or adding a sedating drug which synergises with the opioid effects. The second one is more simple - sedating 1st generation antihistamines, benzos, muscle relaxants etc all do it; combining CNS depressants greatly increases your risk of overdose however so be careful. OTC in the UK something like promethazine is a good bet (Phenergan or Sominex). If you're not looking for sedation, benzos really aren't a great idea, but then neither would sedating antihistamines be either really..

Dihydrocodeine is metabolised by a liver enzyme called CYP-2D6. If you inhibit that enzyme, DHC is metabolised more slowly, therefore remaining in the bloodstream for longer and potentiating the effects. Cimetidine is an antacid which does this but unfortunately in the UK it has been replaced by ranitidine which does not affect liver enzymes. Promethazine and some other 1st generation antihistamines (chlorpheniramine, diphenhydramine) also inhibit CYP-2D6 and potentiate DHC in that way as well.

I can't think of any reason why Mylanta would potentiate dihydrocodeine. Check the opioid potentiation megathread as Cane suggested for more ideas.

I would also not say that DHC is "just shit" compared to codeine; people vary pretty markedly in their response it seems but I find it to have more depth than codeine somehow; I know people with pretty large tolerances who really enjoy it, and people with low tolerances who don't get much from it at all. YMMV. Remember to start with a low dose if you're not familiar with it.
 
Cane2theLeft said:
I don't see how mylanta could potentiate opioids... it sounds like someone found out about cimetidine (another antacid) being a good potentiator and assumed other antacids are and spread bullshit.

I could be wrong but don't know of any mechanism that would cause aluminum, magnesium and simethicone to potentiate opioids. In some guide to using opioids it was printed like a decade ago that naproxen can make opioids stronger (meaning it could increase the analgesia) and I see threads now and then claiming it's a potentiator as well when it doesn't synergize OR increase the effects via enzyme inhibition/induction.
Click to expand...

I started promoting using antacids in Australian Drug Discussion, and it has worked very well for me with codeine and oxycodone. I got the idea from studying pharmacology, here is how it helps:

Most drugs need to be non-ionized to cross cell membranes; the phospholipid bi-layer is very good at keeping out ions and certain other molecules and when cells do need certain ions there are active transport systems for this to occur.

Due to this, a drug like codeine that has a pKa of around 9 will not be absorbed well until it leaves the acidic stomach and enters into the duodenum and small intestine where the pH is raised (more basic). This is because in the stomach, where the pH is commonly around 1-3, codeine is completely ionized and hence will not cross cell membranes well. When we get into the more pH basic parts of the digestive tract, a portion of the total of consumed codeine will become non-ionized and be able to start diffusing.

By taking an antacid and lowering the pH of the stomach contents, the absorption of the drug happens faster and in my experience perhaps a little better as well.

This page should show on the right hand side the pKa calculations for codeine where you can see what state a % of codeine will be in at a given pH. If that diagram does not come up, click on manage calculations and select pKa.

The inverse of this is true as well; aspirin (acetylsalicylic acid) is well absorbed in the stomach because at the usual very low pH range the substance is non-ionized and hence crosses the cell membranes easier then when it is ionized.

physcra said:
Thanks for the reply. I'm looking for sumin to use in the day so the less sedating the better . Cheers mate
Click to expand...

To echo C2theL, if you potentiate a sedating drug then inherently the experience is going to be more sedating.
 
^ That is really interesting, thank you :D love a bit of pKa chat before breakfast :)
 
effie said:
Phsycra, there are essentially two types of potentiation, as Cane mentioned - inhibiting/inducing enzymes responsible for the metabolism of the opioid, or adding a sedating drug which synergises with the opioid effects. The second one is more simple - sedating 1st generation antihistamines, benzos, muscle relaxants etc all do it; combining CNS depressants greatly increases your risk of overdose however so be careful. OTC in the UK something like promethazine is a good bet (Phenergan or Sominex). If you're not looking for sedation, benzos really aren't a great idea, but then neither would sedating antihistamines be either really..

Dihydrocodeine is metabolised by a liver enzyme called CYP-2D6. If you inhibit that enzyme, DHC is metabolised more slowly, therefore remaining in the bloodstream for longer and potentiating the effects. Cimetidine is an antacid which does this but unfortunately in the UK it has been replaced by ranitidine which does not affect liver enzymes. Promethazine and some other 1st generation antihistamines (chlorpheniramine, diphenhydramine) also inhibit CYP-2D6 and potentiate DHC in that way as well.

I can't think of any reason why Mylanta would potentiate dihydrocodeine. Check the opioid potentiation megathread as Cane suggested for more ideas.

I would also not say that DHC is "just shit" compared to codeine; people vary pretty markedly in their response it seems but I find it to have more depth than codeine somehow; I know people with pretty large tolerances who really enjoy it, and people with low tolerances who don't get much from it at all. YMMV. Remember to start with a low dose if you're not familiar with it.
Click to expand...

^Epic post. printing out and framing.
 
I have no means to refute what you're saying blondie but I do remain a little skeptical about the practical benefit to this. I was searching around a bit just now and with drug interaction checkers, they report minor reduction in the effect of phenothiazines (such as promethazine) bioavailability when mylanta is taken with them due to the same concept you just explained and didn't mention any appreciable impact on the strength of the codeine in codeine/promethazine combination products when taken with mylanta.

Given the ubiquity of warnings for grapefruit juice for example with drugs metabolized with those enzymes and how common drugs such as codeine and antacids such as mylanta are used, I would think this would be better documented and patients would be warned in monographs included with prescriptions and so forth. Obviously given my lack of education on the subject, I can't disprove what you're saying scientifically but it would seem logically if this had a clinically significant effect that it would be better documented and patients made aware.

I don't doubt that you have a firm grasp of the science behind this (at least relative to myself ;)) but how pronounced of an effect will this have and if it IS pronounced, how do you explain why this isn't publicized more?
 
^ It doesn't make a huge difference but it is definitely noticeable and worthwhile enough that it's something I do every time I consume codeine; I am not the only one who has noticed this as well as several people in AusDD I encouraged to try it have had positive results, this extends to their use of H2 antagonists as well for a similar reduction of stomach pH.

There are already warnings on antacids not to take them within a certain time frame of taking other medications unless advised to by a doctor, and for medications where the effect is known to be particularly significant pharmacists have specialized warning stickers. This is here in Australia though, packaging and labels may be different in other countries.

I don't think the effect is significant enough with codeine for it to warrant being warned about, and whereas grapefruit juice could cause serious problems for those who already have problems clearing drugs this interaction is less likely to do that. Here in Australia we also don't put warnings about grapefruit juice on opioids, only on Lipitor and a few other blood pressure and cholesterol type medications.
 
Thanks for the clarification.

Does this apply to other opioids as well? Do you have any references for pKa calculations for other opioids?

ETA:

Just found this site which I believe is a bit of support for what you're saying.
 
Last edited:
^ You should be able to use chemicalize.org for pKa calculations for most chemicals and it seems to be very accurate; google is also handy.

The diagram that chemicalize shows I really like, also now you can hover your mouse over the lines on the graph and see the exact percentages at each point.

Here is a PDF that I quickly checked and has multiple opioids among many other drugs: pKa's OF DRUGS AND REFERENCE COMPOUNDS


You can perform some calculations on percentage ionized via this web page, as long as you can determine whether your compound is acidic or basic.

ETA: Saw you question about other opioids. This rule applies to all drugs that can be taken orally; those that are ionized at an acidic pH will not absorb well in the stomach whereas those that are non-ionized at a low pH will absorb well in the stomach and not so well in the more basic parts of the GI tract. There are sometimes other factors at play here, for example if a drug takes advantage of an active transport mechanism or some other method of diffusion but these examples are pretty rare, especially for orally taken drugs, and I can't think of any examples off the top of my head.
 
Very interesting! I really appreciate these resources and your clarification and I would like to apologize for calling out those referencing mylanta as a potentiator... clearly I didn't know what I was talking about ;)

Not that it's an excuse, but often reading claims on here that have been repeatedly debunked (what I refer to as 'junkie science), I am quite skeptical about new information like that which I haven't come across around here or in my education (which is admittedly and unfortunately too limited on the science).
 
^ No problems at all comrade! Even if you think your education in science is limited, questioning things and wanting to see sources and understand how/why shows that you have a scientific mind which I think is very important for us to have given how much misinformation is out there. :)

I know what you mean about junkie science as well... it can be disheartening sometimes to hear the same falsehoods being promoted as fact a lot of the time.
 
Hi

Cheers for da responses guys. So if I went to a chemist what wud be the best thing I cud ask for just to increase the warm buzz not the sleepiness do they still sell first Gen antihistamines?

Thanks again
 
^ Where are you from? Most places should still sell them, here in Australia we still have promethazine, diphenhydramine, chlorpheniramine, doxylamine, etc. all over the counter.

They will all increase sedation though.

There won't be much you can do to increase the 'warm buzz' and not increase sedation. You could maybe try grapefruit juice to extend the experience, I'm not too sure on the metabolism of DHC and whether this would be effective though. After a little bit of searching, I'm guessing that GJF won't do much to help you.
 
^ in the UK promethazine is sold as Phenergan (for motion sickness mostly) or Sominex (for sleeping) and is a good choice. I can't remember the brand name for diphenhydramine.. or Piriton/chlorpheniramine but that isn't as good.

I don't think GFJ works on the right enzyme.. promethazine is a weak inhibitor of CYP-2D6 though I believe along with some other 1st generation antihistamines.

edit: just take the recommended dosage - taking too high a dose of 1st generation antihistamines can cause delirium and other unpleasantness from anticholinergic action.
 
^ Yeah I didn't think GFJ did... so probably best to skip that one OP.

CYP2D6 metabolizes dihydrocodeine into dihydromorphone, so it's probably a good idea not to inhibit that in this case. So the promethazine should be taken a little bit after the DHC. Won't be as drastic as taking it at the wrong time with codeine, which it can completely ruin in my experience. :\

Oh and promethazine is Phenergan here as well, we don't have the Sominex brand though and it's not sold for sleep really due to it's half-life. Doxylamine and diphenhydramine are more popular for that purpose here.

Why don't you think chlorpheniramine is as good effie? It's not as sedating that's for sure, I found that it works well to reduce histamine related side-effects and nausea with opioids without being overtly sedating. Most of the time now though I want a very sedating antihistamine so I go for promethazine or doxylamine. :)
 
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