Differential Response to Opioids

[turkeyjerky]

Hey all,

I'm and EM doc and hoping y'all could answer a quick question for me. As I'm sure is a surprise to absolutely nobody here, we often get patients who claim "x never works for me, only the D drug does". I've always maintained that this is either a) a sign of drug-seeking behavior or b) a dosing related phenomenon, eg it's logical that 2 mg of hydromorphone is more efficacious than 2 mg of morphine.

However, I listened to a pain lecture a little bit ago where the guy was talking class differences in the response to nsaids, and I was wondering if anything has actually been described for opiods? (let's leave aside methadone for the purposes of discussion here, as I understand there actually is something to that one).

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[lobelsteve]

Putative opioid receptor subtypes are suggested mainly by: (i) different modulation by pharmacological agents of functional responses (in vivo, ex vivo, and in vitro); (ii) an incomplete cross-tolerance profile between different receptor agonists; (iii) complex binding characteristics including: shallow ligand displacement curves and differential irreversibility of ligand binding. However, these suggestions must be set beside the molecular evidence of (i) only single receptor encoded by a single gene and (ii) genetic knockout of the single receptor gene results in a loss of ligand binding and function associated with that receptor. That there are physiological, pharmacological, and behavioural differences with ligands of different classes is not in doubt, but we do not believe that, based on these differences, receptor subtype status can be ascribed. Moreover, there is at least one example of possible misclassification (putative κ3 is likely to be NOP).

We believe that these pharmacological subtypes can be reconciled with the molecular data by considering (i) alternative splicing, (ii) receptor dimerization, (iii) interaction with other proteins and biased agonism, and (iv) combinations of (i)–(iii) (Fig. 3).

Opioid receptor subtypes: fact or artifact?

Abstract. There is a vast amount of pharmacological evidence favouring the existence of multiple subtypes of opioid receptors. In addition to the primary classi

academic.oup.com

 

[Ducttape]

from a practical standpoint, for the most part, agree with OP conclusion. but a few drugs can be different.

some people are slow metabolizers of codeine due to low cytochrome P4502D6 and as such will not "feel" a response from codeine.

there are a few people and one particular ethnic group that is have high levels and are fast metabolizers, and this can lead to overdose at therapeutic doses.

likewise with tramadol. some people cannot metabolize tramadol in to the active form of O-desmethyltramadol.


all of the pure agonists given in the ER should be pretty similar.


now remember that opioids are notoriously less effective for neuropathic pain.



as an ex-ER doc, i also agree that someone saying that morphine or fentanyl doesnt work probably did not have a high enough dose, and someone saying that "only demerol works" or "only dilaudid IVP very fast works" is probably drug seeking.

especially the "only demerol" quote.

 

[callmeanesthesia]

Several of the common oral opioids are prodrugs requiring hepatic metabolism to the active form. This is not the case for morphine or fentanyl (or dilaudid).
Redheads really do have a higher dose requirement, by about 20%.
If someone tells you lidocaine doesn’t work well on them, believe them. Or, if you numb them up well with lidocaine for a minor procedure and they still jump and scream, and it feels sharp to them, put some 0.25% bupivacaine in there instead. Give it a few minutes to kick in and you’ll be amazed at the difference. Ask them if the dentist has a hard time numbing them and has to inject them four or five times.

 

[Ferrismonk]

There is evolving science on this. In addition to genetic metabolism differences, opioid receptor subtypes doesn't seem to be that important after all. There does appear to be something to the ligand differences.

Anecdotally, Hydromorphone and Oxycodone have always seemed to create more euphoria at the equinalgesic dosing of other opioids in my experience.

 

[painfree23]

from a practical standpoint, for the most part, agree with OP conclusion. but a few drugs can be different.

some people are slow metabolizers of codeine due to low cytochrome P4502D6 and as such will not "feel" a response from codeine.

there are a few people and one particular ethnic group that is have high levels and are fast metabolizers, and this can lead to overdose at therapeutic doses.

likewise with tramadol. some people cannot metabolize tramadol in to the active form of O-desmethyltramadol.


all of the pure agonists given in the ER should be pretty similar.


now remember that opioids are notoriously less effective for neuropathic pain.



as an ex-ER doc, i also agree that someone saying that morphine or fentanyl doesnt work probably did not have a high enough dose, and someone saying that "only demerol works" or "only dilaudid IVP very fast works" is probably drug seeking.

especially the "only demerol" quote.

The chance of a patient not being able to metabolize both codeine and tramadol seems very low, so I would try one or the other. It’s two different enzymes and unlikely that they can’t metabolize either.

 

[deleted875186]

I don’t believe traditional opioid agonists have any differential effect, just different onset, peak effect, and duration, hence why people say hydromorphone works better than oxycodone, hydrocodone, etc. Also hence why I don’t use PO hydromorphone as an outpatient medication for anyone.

I don’t think there is an accurate conversion from the fentanyl drugs to traditional agonists, fentanyl is just much more potent snd the duration snd onset is so much shorter it is impossible in my opinion to have an equipotent dose of fentanyl and oxycodone/morphine/hydromorphone.

 

[turkeyjerky]

Thanks guys, sounds like I was mostly on the right track. Yeah, knew about codeine and trammadol (pretty much never use these drugs tbh).