Opioids Mixing Opioids? receptor question

[Deathly]

If I am taking multiple opiates at once will the opioid effects of the two drugs be combined or will the drug with the higher affinity to the opioid receptors nullify or reduce the the opioid effect of the drug with a lower affinity?

For example, say I take 200mgs of morphine orally and 30mgs of hydromorphone orally at the same time. Say 30mg of hydromorphone is equal to 120mg of morphine, this means I have taken the equivalent of 320mg of oral morphine.

Can I expect the opioid and analgesic effect to be equivalent to 320 mg of morphine, or will the hydromorphone out compete the morphine and leave me with 120mg of oral morphine equivalent effect? or vice versa? Will the drugs share the receptor perfectly or will there be some nullified or wasted?

I know this question is very dependent on the Pharmacokinetics of each drug, so which opioids can be used together and which will block others and to what extent? Is the affinity directly correlated to the drugs per mg equivalent?

thanks

 

[Jktm]

IME you don't get a blockade effect unless one's really potent...and you're not going to saturate all your receptors. If you combine opioids, just make sure their relative affinities aren't too different...And just be careful...

 

[mrflowers00]

idk about morphine and hydromorphone but oxycodone and hydromorphone potentate eachother IME

 

[tricomb]

GREAT question, I almost posted this exact same question a while back.

 

[cook]

Well for example demanding pain patients there is some kind of "base" opioid for example fentanyl transdermal and oxycodone for breakthrough pain. So at least the analgesic effect is potentiated this way.

And then again low-dose buprenorphine with very high affinity also works with other agonists too. It's just not that simple that something with higher affinity would always kick out everything else, i'm not an expert but I would guess this has something to do with the total number of receptors. If you have a super high dose of something and then try to bring on some other opioid in the system with lower affinity, you would get no effect. But at lower doses it's different cause you still have some "free" receptors.

Recreationally, I don't like to combine any opioids. It just doesn't seem to produce any more desirable effects. There are some exeptions that I know though, for example tramadol and codeine which work great together recreationally.