Tagamet and Codeine Yes or No?

[drminaq]

my next question is would a Cyp 450 inhibitor like cimetidine block the effects of codeine or potentiate them?
Thanks for the help!:D

 

[JamtasticX]

I'd have to read up on it, but I'm pretty sure that codeine is one of the drugs that tagamet doesn't work for, because cyp3a4 is needed to convert it into morphine. So if I'm correct tagamet would ruin the effects of codeine.


Although that aside, tagamet usually helps with opiates, and makes them break down slower. It would be helpful as long as it's not needed to be converted.

 

[drminaq]

Those were my thoughts exactly but I will let you know as I really have a limited understanding of these processes.

 

[JamtasticX]

Yea, I was right that i t needs to undergo demethylation (since codeine is methylmorphine).

Only thing is the last line says administering methylmorphine with cyp3a4 inhibitor would increase the levels of morphine? Wouldn't that come from allowing cyp2d6 to have more methylmorphine to demethylate, since none is being taken up from cyp3a4?

Eh, regardless, see below for details

http://www.ncbi.nlm.nih.gov/pubmed/8818573

Codeine is metabolized by glucuronidation, by O-demethylation to morphine, and by N-demethylation to norcodeine. The enzyme responsible for the O-demethylation to morphine has been identified as cytochrome P4502D6 (CYP2D6). The purpose of the present study was to identify the specific P450 enzyme responsible for codeine N-demethylation. Microsomal preparations (250 pmol of P450) obtained from 12 human liver donors were incubated with 20 microM codeine and analyzed for norcodeine formation. Codeine N-demethylation activity was linearly correlated with nifedipine oxidation activity (r = 0.90, p < 0.001), a marker of CYP3A4, but not with codeine O-demethylation, a marker of CYP2D6. Preincubation with troleandomycin (50 microM), or gestodene (50 microM) inhibitors of CYP3A4, decreased the rate of production of norcodeine by 60 and 45% compared to control values, respectively. Similarly, ketoconazole (10 microM) and erythromycin (10 microM) inhibited codeine N-demethylation by 75 and 35%, respectively. In contrast, the presence of quinidine, sulfaphenazole, or diethyldithiocarbamate in the incubation mixture had no effect on norcodeine formation. Preincubation with antibodies raised to CYP3A4 (5 mg lgG/nmol P450) caused 96% inhibition of norcodeine production, whereas preimmune IgG or antibodies raised to CYP2A6 and CYP2C had no effect. Additionally, significant norcodeine production was observed with purified CYP3A4 derived from human liver microsomes. In conclusion, codeine N-demethylation activity cosegregates with CYP3A4 activity. Coadministration of codeine with selective inhibitors of CYP3A4 may result in increased morphine production and enhanced pharmacodynamic effects due to shunting down the CYP2D6 pathway.

 

[drminaq]

Thanks...I was pretty sure that was the case...it has been 20 minutes since codeine dosage and 1 hour since tagamet dose of 200 mgs. I feel the effects but they are significantly decreased. Not a recommended combo. One done out of lack of information, albeit. Thanks