Warning - possible SNRI and codeine reaction UPDATE: loratadine and SNRI interaction?

[Evad]

Just bounced this over fro EADD to see if any of the neurochem bods can add any insight

 

[bpayne]

strange, I wouldn't have thought that the Codeine would've interactive with an snri either as I take Tramadol with codeine together quite a bit, however I fret a lot over doing ANY other combo's like I have some acid I still haven't taken even though I took a whole month off of tramadol recently, but I was doing mephedrone at the time. anyways, I suppose it could be the loratadine, but allergy medication and snri's I thought would be just fine, any possibility it could be just a freak reaction to the
Venlafaxine? how long have you been on this med? sorry if you've already posted that info, it's early and my coffee hasn't kicked in yet

 

[negrogesic]

This does not sound like 'serotonin syndrome'. A true hypertensive crisis is life-threatening, and is unlikely to occur with the drugs listed. I have seen fatal hypertensive crisis from combos of tramadol and other serotonergics, but only at very large doses. How do you know what serotonin syndrome "feels like"......blood pressure, heart rate, respiration rate, pupil size, degree of diaphoresis, GI manifestations , etc.....without any data aside from the subjective "it feels like mild serotonin syndrome" and the list of compounds ingested, it is hard to claim that this was another more than perceptual adverse reactions......A oral body temp of 38c is by no means high, and would only be a concern if it was in concert with other measurable abnormalities. Extended low grade fever (weeks) with no other symptoms is a concern, this is known as an FUO and these are notoriously hard to figure out.....(had a few cases, one was a vegetation, another fungal).

Anti-chol toxicity and hypertensive crisis both present delrium, but they are very different animals. Cholingeric toxicity is somewhat rare (poisonings, o-phosphate exposure), and would not present from the drugs listed. How did this end up in ADD....

 

[cherrycolouredfunk]

I just found this when I was looking up side effects, as Venlafaxine is making me feel REALLY sick just now. I've only just started taking it today.

Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as alpha2-adrenergic receptor, and was shown to increase pain threshold in mice.

 

[effie]

This does not sound like 'serotonin syndrome'. A true hypertensive crisis is life-threatening, and is unlikely to occur with the drugs listed. I have seen fatal hypertensive crisis from combos of tramadol and other serotonergics, but only at very large doses. How do you know what serotonin syndrome "feels like"......blood pressure, heart rate, respiration rate, pupil size, degree of diaphoresis, GI manifestations , etc.....without any data aside from the subjective "it feels like mild serotonin syndrome" and the list of compounds ingested, it is hard to claim that this was another more than perceptual adverse reactions......A oral body temp of 38c is by no means high, and would only be a concern if it was in concert with other measurable abnormalities. Extended low grade fever (weeks) with no other symptoms is a concern, this is known as an FUO and these are notoriously hard to figure out.....(had a few cases, one was a vegetation, another fungal).

Anti-chol toxicity and hypertensive crisis both present delrium, but they are very different animals. Cholingeric toxicity is somewhat rare (poisonings, o-phosphate exposure), and would not present from the drugs listed. How did this end up in ADD....

I know it wasn't serotonin syndrome. I meant the symptoms I had immediately made me think of that, and made me ponder whether they were caused by a similar process. Serotonin syndrome is a continuim I believe, with hypertensive crisis and death at the severe end?

My post was not particularly well worded or thought out, but I wasn't posting it in ADD so I didn't have my scientific hat on. Was just warning my fellow EADDers of a possible potential drug interaction. Am aware it could be random, but the flushing/sweating/pyrexia for half a day was certainly bizarre (and I'm medically minded, not an idiot when it comes to symptoms.)

I do know all about pyrexia of unknown origin, luckily my temp has normalised! I know that 38 is not worryingly high, but (as am sure you know) 38 is considered pyrexial and definitely abnormal. Some people consider 37.5 pyrexial, I don't, but 38 def makes me think something is going on. A one off episode of pyrexia in a non-hospitalised patient with no obvious symptoms of infection just seemed odd, along with the other symptoms I had..

The thing that really made me wonder about the cause was that I had recently taken a combination of drugs which may have interactions I was unaware of. The extreme flushing and sweating, subjective tachycardia and agitation all concerned me and having had such a large histamine reaction to codeine the night before, plus taking loratadine and having just started on an SNRI was grounds to enquire whether anyone thought this could be a drug interaction.

Mods feel free to move this post back - it wasn't writted for ADD and I appreciate it is written in a particularly unscientific style. It was moved here in the hope that someone with good pharmacology knowledge could shed any light on any possible dangers of venlafaxine/high dose codeine/loratadine (this would be harm reduction after all!) but I appreciate how frustrating it must be having your forum clogged with non advanced stuff.

Edit: bpayne, I've been on it a few weeks so unlikely to be a reaction just to that. Cherry, that all sounds interesting, not too sure what the implications are though!!

 

[AC.e]

Codeine overdose

I know it wasn't serotonin syndrome. I meant the symptoms I had immediately made me think of that, and made me ponder whether they were caused by a similar process. Serotonin syndrome is a continuim I believe, with hypertensive crisis and death at the severe end?

My post was not particularly well worded or thought out, but I wasn't posting it in ADD so I didn't have my scientific hat on. Was just warning my fellow EADDers of a possible potential drug interaction. Am aware it could be random, but the flushing/sweating/pyrexia for half a day was certainly bizarre (and I'm medically minded, not an idiot when it comes to symptoms.)

I do know all about pyrexia of unknown origin, luckily my temp has normalised! I know that 38 is not worryingly high, but (as am sure you know) 38 is considered pyrexial and definitely abnormal. Some people consider 37.5 pyrexial, I don't, but 38 def makes me think something is going on. A one off episode of pyrexia in a non-hospitalised patient with no obvious symptoms of infection just seemed odd, along with the other symptoms I had..

The thing that really made me wonder about the cause was that I had recently taken a combination of drugs which may have interactions I was unaware of. The extreme flushing and sweating, subjective tachycardia and agitation all concerned me and having had such a large histamine reaction to codeine the night before, plus taking loratadine and having just started on an SNRI was grounds to enquire whether anyone thought this could be a drug interaction.

Mods feel free to move this post back - it wasn't writted for ADD and I appreciate it is written in a particularly unscientific style. It was moved here in the hope that someone with good pharmacology knowledge could shed any light on any possible dangers of venlafaxine/high dose codeine/loratadine (this would be harm reduction after all!) but I appreciate how frustrating it must be having your forum clogged with non advanced stuff.

Edit: bpayne, I've been on it a few weeks so unlikely to be a reaction just to that. Cherry, that all sounds interesting, not too sure what the implications are though!!

500mg of Codeine is way to much, if your looking to get a opitate buzz codeine is the wrong drug to use, Hydrocodone or Oxy is much safer,
requires a far smaller dose to get you a better effect helping to avoid taking a stupid amount like 500mg.

 

[AC.e]

500mg Codeine is a bit much, think you had a codeine overdose, try Hydrocodone or Oxy insted both require much less with better effects avoiding the need to take a stupid amount like 500mg, if your looking for a opitate buzz which is what it looks like Codeine is not a good drug to use.

 

[NeighborhoodThreat]

500mg of Codeine is way to much, if your looking to get a opitate buzz codeine is the wrong drug to use, Hydrocodone or Oxy is much safer,
requires a far smaller dose to get you a better effect helping to avoid taking a stupid amount like 500mg.

For a person without opiate tolerance 500mg of codeine is too much. The OP in this thread had (and has) an opiate tolerance.

 

[Limpet_Chicken]

Some people get quite good effects from high dose codeine. Depends on the individual's biochemical makeup. A dose that is very recreational in some people is anything but in others.

re: serotonergic effects of oxy, could someone clarify? is oxycodone a 5HT releaser, blocker of SERT, or a direct agonist at some or other 5HT receptor subtypes? I don't want any nasty surprises taking my pain meds and a serotonergic drug. Especially since I take antihistamines sometimes to deal with itching as a side effect from my OCs and oxynorm (fexofenadine)

For someone with no tolerance, 500mg is definately enough to have one throwing up, itching like crazy etc. But with some degree of tolerance, high dose codeine can be quite recreational and without too many side effects. It is constipating as hell though.

 

[polarbearsarecool]

venlafaxine and codeine probably share enzymatic interaction via codeine metabolism or morphine metabolism and as we all know some anti depressants can cause serotonin syndrome/histamine syndromes via elevation of plasma metabolites as well as venlafaxine sharing a very similar structure to tramadol, it functions probably just as tramadol does, sharing a opiate-snri like metabolite.. So via double opiate histamine interactions, mutual potentiation via enzymatic interactions, this combo is no good

 

[Poodles!]

Oh effie! You big silly (although I sympathise, I've done my fair share of boners when it comes to drug interactions... But you're an EADDer that's on serotonergic antidepressants known for, amongst other things, their brutal effect on the Cytochrome P450 chaps. And EADDers are known for, well y'know, it's hard to put it into words as I've run out of MDPV and I REALLY NEED SLEEP and shit. Yeah.

Lets assume for a moment that you have potentially eliminated CYP involvment of codeine metabolism. Now I've never had a go on your liver before - although this is the equivalent chat up line for nerds to "let's 'ave a go on ur tits love" for a fat slapper with low self esteem and a belly full of VK's (the cherry one is the one to look out for, it reminds me of this... memories) - so I don't know what you're metabolism is like, but let's assume the worst for a moment:

You could be missing out on 40% of codeines metabolism through the CYP guys (I remember this stuff by thinking of enzymes as little "bender from futurama" robots bending the molecules and breaking bonds with toolbags of vitamins and whatever else they need to do to complete their little task. The whole factory being me with my digestive system and metabolism being conveyer belts and stuff with the end of the line being loading the finished products into the delivery van. The delivery van being a toilet, the finished products being being boxes of shit and jars of urine with the toxic gases belowing from the dirty great chimneys) and of course there's possibility that you've taken anything that is competetitively metabolised via UGT2B7 although clearly nothing is inhibiting it to any great degree (though some AD's do, ie buproprion). I imagine your plasma levels of Codeine could have reached some pretty insane levels fro 500 mg...

Very useful page: http://www.pharmgkb.org/pathway/PA146123006

Oh, and where it says that codeine-6-glucuronide has roughly the same affinity for MOR, it's talking bollocks. You've got between 50% and 80% of the codeine being metabolised to C6G which has been shown to be roughly equipotent as an analgesic as codeine.

I experimented with this by taking a silly amount of sertraline (yuck) which is a pretty strong CYP2D6 inhibitor one evening and then two 30/500 coco's the following morning. This provided great analgesia and a subtle but pleasant warmth that would have been difficult to notice if it were not for the fact that I could feel that unmistakable point at which an opiate begins to take effect, and I actually felt "normal" for the first time in a long time... I tried this another time a few hours after 300 mg of buproprion SR (inhibitor of both CYP2D6 & UGT2B7) with a gram of milk thistle extract (80% Silymarinan) ~20 minutes before dosing. All I got was an itchy nose.

I might knock a few back now actually. CBA with a CWE for 2 or 3 grams of paracetamol. Milk Thistle + N-Acetyl-L-Cysteine + L-Glycine + Alpha Lipoic Acid + whey protein (pretty high L Glutamine) = perfect excuse to be lazy!