# Loperamide + Quinidine?



## TyrosineKinase (Jan 20, 2010)

I was recently prescribed quinidine/dextromethorphan for pseudobulbar affect. Then I came across something that stated that quinidine + loperamide allows loperamide to cross the BBB. This produces respiratory depression, but does anyone know if it also allows for pain reduction as well?

My doctor who perscribed this medication (nuedexta) knows that I have access to pharmacological books at my university and sort of gave me a few "winks" and while I'm only doing my first years at my masters, I still don't really have the knowledge to understand the basics of whether combining the two would produce pain relieving effects yet. Even if it did, I wouldn't know what dosage would be considered safe.

It seems as though if the combination produces respiratory depression, then it would be acting on the central nervous system, but I'm not sure if it carries with it the pain relieving properties. I've been trying to find research that deals with this, but cannot find anything related to the pain relieving side of things.

Thanks for help and have a great day.


----------



## istayhome (Apr 4, 2012)

You're on the right track and the answer to you question is that it kinda sorta works. Loperamide does cross the BBB but P-glycoprotein kicks it out of the brain just fast as it enters so it doesn't have any CNS effects. The way to get CNS effects is to first flood your body with Loperamide 60-100 mg. Then you need to inhibit P-glycoprotein so the Lope stays in your brain longer. The quinidine will inhibit P-glycoprotein but it only slows down the action of it removing the Lope from your brain. 

It does work but you don't get very strong effects. People usually only do this to ease opiod withdrawals. Having to take so much Loperamide and the minimal action makes it too much of hassle for anyone to use it. You can give it a try, building tolerance takes a while so if it does work to relieve your pain enough than that is good. 

I actually just tried this combo for the first time, the effects are very minimal, with no opiod tolerance. People on drug forums talk about this topic a lot for opiod withdrawls.


----------



## TyrosineKinase (Jan 20, 2010)

How much quinidine is needed for this? I have capsules that contains 20 mg dextromethorphan and 10 mg quinidine. Also would the dextromethorphan have any effect on this?

My last and most important question is does this have any life-threatening interactions between cymbalta + (loperamide/quinidine/dextromethorphan)?

Thanks for the help so far


----------



## istayhome (Apr 4, 2012)

loperamide/quinidine/dextromethorphan all are fine together. The dxm at a dose around 150 mg should potentiate it a bit at around with 150 mg. From what I've read you should only need 20 mg of quinidine to be effective with any dose of loperamide. More won't hurt though. 

The only drug interaction to be concerned about is cymbalta and DXM. You run the risk of serotonin syndrome if you take too much DXM. Even 60 mg of DXM seems to potentiate opioids nicely though, so maybe keep the DXM dose low to be on the safe side. You can always take a few more capsules of it if you want to.


----------



## TyrosineKinase (Jan 20, 2010)

Thanks for the response. If I take 20mg of Quinidine, I would have to take 40mg of dextromethorphan, since the capsules come in a ratio of 10mg/20mg each. I am on 60mg of cymbalta daily.

If I were to try this, would it be safer to not take the cymbalta for the day I choose to take the quinidine/loperamide or would that not do anything? Or should I just take the cymbalta with the combination. I guess I'm wondering if the timing of the dosage would mean a lesser chance of Serotonin syndrome (with a greater chance if they were taken closer together and lesser chance if I didn't take the SNRI at all for a day).

I know I couldn't get away with not taking the SNRI for at most, a day, because I suffered from brain zaps and dizziness after tapering from both cymbalta and effexor before.

Thanks for the help and have a great day.

Oh and I almost forgot, are you able to give me the links to where you are getting this information regarding the administration of quinidine and loperamide together? Thanks


----------



## istayhome (Apr 4, 2012)

Just google quinidine and loperamide. You'll find endless posts, threads and articles about the combo on all of the drug forums. There are so many sources I couldn't just provide one, I spent hours reading and comparing information from various sources. 

Are you concerned about the 40 mg of DXM? That is nothing, it certainly wouldn't interfere with Cymbalta, too low of a dose. It might be too low to potentiate, but I have heard of 60 mg potentiating.

I don't think that low of a dose which is just above therapeutic would cause Serotonin Syndrome. I don't think taking Cymbalta the day of or skipping it that day would matter at all. In my experience when taking effexor, if I skipped it for a day to have another drug be more or less effective, it made no difference at all. 

If you want to be on the safe side then 20 mg quinidine/40 mg DXM will be fine with Cymbalta and Lope 40 mg is just a therapeutic dose and there is no risk between that low if a dose of DXM and SSRI's. It is a danger with MAOI's though. It might not potentiate as much as it could, but it would provide some potentiation and reduce tolerance. I have taken higher doses of DXM on Seroquel, probably up to around 200 mg and never had any ill effects, just a mood lift.


----------



## TyrosineKinase (Jan 20, 2010)

Thanks for the information istayhome.

I guess the biggest problem I have come across in my research is this: No one seems to say anything about the analgesic properties of loperamide when used with quinidine, only that it gives respiratory depression that makes it *seem* like its acting on the central nervous system.

At least, that is what I have been reading in the research articles from the journals at my university and online forums.

I don't know if I have missed an article that addressed it or not, but does loperamide acting on the central nervous system automatically give it analgesic properties (since it's an opioid) or just respiratory depression?



> Concurrent administration of P-glycoprotein inhibitors such as quinidine with loperamide has been found to produce respiratory depression, indicative of central opioid action.


For example, this quote. When it says "indicative of central opioid action", does this include analgesic affects?

Thanks, I really appreciate the help. If anyone else has any experience with this please don't hesitate to post either.


----------



## istayhome (Apr 4, 2012)

To your question yes. mostly. It depends on the type of pain. 

For example people who use just loperamide for withdrawals (without the p-gp) find that it relieves all symptoms other than the psychological effects. 

Just Loperamide in higher doses will cause analgesia in the PNS (Peripheral Nervous System) because there are mu-opioid receptors all over the body. So it depends on the nerve supply to where your pain is.

Loperamide+quinidine (as long as you have enough Lope to keep the receptors in the CNS flooded, the lower the opioid tolerance you have the better) will result in CNS analgesia. Many people have experienced this and I know people who are addicted to Loperamide, although it is an easy addiction to break withdrawals are barely noticeable.

"central opioid action" means everything you would expect from morphine. The strength is the only thing I am unsure of if you have a low opioid tolerance then it shouldn't take much with the addition of quinidine for analgesia. 12 mg of Lope should be a good place to start. If you opioid tolerance is sky high then you may need 50-60+ mg of Lope for it to be effective.

A lot of people do find moderate analgesia from 12 mg or so of Loperamide with the addition of some quinidine. hope that helps.


----------



## TyrosineKinase (Jan 20, 2010)

I really appreciate your responses Istayhome. They are quite helpful.

I do have a last question if you don't mind. I didn't think about it until your most recent post.

I have no idea what my opioid tolerance is and perhaps you could help me with this. I was previously on 4 vicoprofen per day, which is 30mg of vicodin for pain to be relieved. I stopped that around May. Then I was put on tramadol about 2 months ago for about a month and I had to take about 150 mg for it to work.

Does that help at all in determining what level of loperamide I should be taking and the level of tolerance I have?

Thanks a lot for your help


----------



## istayhome (Apr 4, 2012)

your tolerance sounds low. and after a month clean from just tramadol, months clean from vicodin I wouldn't expect any tolerance. So probably start around 12 mg of Loperamide and if nothing then work your way up. 

Everyone will have a different base level tolerance but it sounds like yours is average (low). 30 mg/day of hydrocodone is what is expected for a grown adult male with no tolerance.

Let us know what your experience is like. I mostly only hear of people using this to withdraw from other opioids painlessly.


----------



## TyrosineKinase (Jan 20, 2010)

Today I tried two different combinations, once in the morning and once in the evening. I started out at lower dosages because I'm paranoid about things going wrong even though I know the quinidine is an absurdly low dosage.

10mg Quinidine
20mg Dextromethorphan
10mg Loperamide
I didn't notice anything from the above combination

10mg Quinidine
20mg Dextromethorphan
12mg Loperamide
I didn't notice anything from this combination either

Tomorrow I will doing the following in the morning...

20mg Quinidine
40mg Dextromethorphan
14mg Loperamide

And if nothing happens I guess I'll try to up the loperamide more.


----------



## TyrosineKinase (Jan 20, 2010)

I don't know if anyone cares about this or not.

So this morning I tried: 20mg Quinidine, 40mg Dextromethorphan, and 14mg loperamide. I didn't notice much of anything. No reduction in pain symptoms or opioid-like activity going on. Tomorrow morning I would try to up the dosage of just the loperamide more. Perhaps to 18-20 mg.

I'm afraid of uping the quinidine because that means I would have to up the dextromethorphan to 60mg and I think that it might take away from the true test of measuring the effects of loperamide.


----------



## istayhome (Apr 4, 2012)

Yeah, from what I've been reading to get a CNS response frm lope tou have to toally flodd yor rceptors. like 60-100. Extreme and I wouldn't do it personally.


----------



## TyrosineKinase (Jan 20, 2010)

Okay, so I did two new experiments regarding these combinations.

Yesterday, the 25th, I woke up at around 7am. I got a good nights sleep, 10pm-7am. So as soon as I woke up I decided to try the following...
20mg Quinidine
40mg Dextromethorphan
20mg Loperamide

After about 8am I fell asleep until 1pm. I couldn't really tell if there were any analgesic affects because, of course, I fell completely asleep within an hour of taking this combination. And that's right after waking up after a long night of sleep.

Today I tried upping the dosage of loperamide by another 2mg. The same thing pretty much happened, though I didn't sleep as long, however I could definitely tell that there just may be CNS depression going on.

Could quinidine affect loperamide the same way it affects the dextromethorphan? What I mean is, the only reason quinidine is combined with dextromethorphan, in the medication Nuedexta, is to increase the plasma concentration of dextromethorphan. Could it be doing the same to loperamide?


----------



## istayhome (Apr 4, 2012)

Loperamide doesn't peak for 5 hours. For this experiment to work I think you need to take more Loperamide, like 60-100 mg. of Lope and more quinidine. Besides the P-gylcoprotein inhibition I do not know what effects Quinidine has that may additionally affect loperamide.


----------



## TyrosineKinase (Jan 20, 2010)

Hey Istayathome. Thanks for the reply. I don't know if I'm willing to go as high as 60mg along with the quinidine and dextro and cymbalta. I might keep adding 2mg a day from the 22mg (which was my last dosage), until I notice something. Or maybe jump to 30mg.

Or, to be totally comfortable, I'll probably have to taper down from the cymbalta completely to try to get to the 60 mg loperamide because of the interactions with dextro and quinidine.

Where did you find the figure of 5 hour peak for loperamide? In my pharmacology book it states that it has a beak of 2 hours in capsule form and 2.5 hours in liquid, with an onset of 1 hour.

Thanks again for your time. Have a great day.


----------



## istayhome (Apr 4, 2012)

That is what I've heard reported from people who do say they have taken it in high doses with some success, they compare it to methadone, with a 2 hour time to onset and a peak in around 5 hours.

Who knows, people might be making it up there's still not really a confirmed report of this working. I personally wouldn't take that much either. They idea is to have so much loperamide in you that it will keep bouncing through the BBB faster than the P-glycoprotein can push it out.

I think taking high amounts of quinidine is dangerous too so look into that.


----------

