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Calls for Ibuprofen sales restriction

Messages
38
Location
Wales
An article has just been published calling for the restriction of sales of Ibuprofen. A Danish study suggests that it can increase the risk of cardiac arrest by 31%.

Prof Gunnar Gislason of the University of Copenhagen, who led the study, called for tighter controls on the sale of ibuprofen and other NSAIDs. He said: “Allowing these drugs to be purchased without a prescription, and without any advice or restrictions, sends a message to the public that they must be safe."

https://www.theguardian.com/society...trictions-study-increased-cardiac-arrest-risk

As someone who goes through a lot of Ibuprofen, it's something I'll be keeping a close eye on. The thought of having to go to the GP and get a prescription for it every time gives me shivers.
 

RogerBlack

Senior Member
Messages
902
OMG soon there will be nothing left to ease the pains of life, it's BS like this that fuels the rise in 'alternative' treatment in all its colours

It's not wholly BS.
There is clear indication that there is in fact a risk for some patient groups and patients.
This is not a trivial risk, and it's likely (due to the patient population) that it's directly killing a significant number of people a year through heart attacks, and major intestinal bleeds.

What's needed is safer inexpensive painkillers.
https://www.ncbi.nlm.nih.gov/pubmed/28025218 - for example.
Of those taking painkillers, the risk of an out-of-hospital heart attack rises 30% or so.

There are a number of problems with these studies, but the effect seems to be real.
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I was warning about just this issue in the 90s, based on the biochemistry. They are blunt instruments, and work by attacking cyclooxygenase in various ways. I predicted Vioxx would be problematic. It was. The same principle should apply to most of these drugs, because the mode of action is similar.

Yet intermittent use should not be a major issue, again based on the biochemistry. I think heavy long term use will typically raise the risks, sadly. I was happy to use Vioxx when it was around, and it was about the only drug that helped my pain, but I only used it very occasionally, and never two days in a row.

This does need to be put into perspective. These drugs are shown to raise relative risk, this is not absolute risk, and I have not tracked down what that would actually be. My blind guess is about a 10% actual increase in risk for chronic users, presuming these findings are about right.

In any case many of these drugs are less effective than cannabis for many people, especially those with fibromyalgia (according to patient surveys).

Drug companies can be expected to lobby to leave these drugs available over the counter.
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
This may be somewhat off topic because this post is about using ibuprofen for endometriosis pain, not ME/CFS pain. But there seems to be a lot of overlap between ME/CFS and endometriosis so I'm posting anyway.

In my case, NSAIDs were a lifesaver for endometriosis pain. My limited understanding is that endometriosis pain has something to do with a certain type of prostaglandin. Acetaminophen did nothing for my pain. Aspirin, a weaker NSAID, did a little bit. Ibuprofen helped and prescription NSAIDs were even better.

I was talking a LOT of ibuprofen daily (I think twice the over the counter max but I had discussed this with my doctor). And then I took prescription NSAID ketorolac (Toradol) for the 6-7 days of my period, when the pain was at its worst. I was supposed to take ketorolac for no more than 5 days. But I just couldn't stand it so I took the extra risk.

I think I would have committed suicide if I'd had to stand that pain without any drug at all. I'm sure it was not good for me but neither was that pain. Fortunately, my excision surgery in 2000 which removed the endo (or at least what was visible) reduced the pain to almost nothing.

Ironically, there was no resistance to giving me painkillers AFTER surgery. But the post surgical pain was nothing. I barely needed even a couple ibuprofen, and didn't even use the hydrocone (Vicodin). But since the surgical incisions were visible that was "real" pain. The endometriosis pain was invisible and so it was often dismissed or minimized (not by my endo surgeon, though).

Anyway, just one data point to consider. At the time all I knew about were the listed side effects. But even if I'd known about risks for cardiac arrest I think I would have still taken it.
 

PNR2008

Senior Member
Messages
613
Location
OH USA
What gets me are the doctors that probably caused the heart attacks by prescribing NSAIDS at large dosages. In 1988 when I got CFS/ME my rheumy couldn't give me enough. I took 800MG of Ibuprofen up to three times a day, then time released aspirin, Voltarin, naproxen and they buzzed my head and only helped with the little inflammation I had. Finally he put me on Darvacet with reservations even though it worked.

Well that was pulled off the market and where do I go from there? You've got it Vicodin. The mortal sin of the pain set. Well that was 20 years ago and I'm not dead yet from Vicodin but I did have Takotsubo Cardiomyopathy about a year ago which is not from clogged arteries, it isn't as rare as first thought but little is known about it. I can tell you that my left ventricle is still enlarged.

I thought ME was exhausting, try Takotsubo and you may feel you've digressed 20 years. I'm still recovering and it could happen again. Well guess who gets crap at the ER for taking Vicodin? The Dr. said he'd had to report me, To my Mom? No to my state.

By the way he barely knew what POTS was and never heard of Takotsubo Syndrome. I don't know who the real losers are here.
 
Messages
516
I followed the link and it says:
“Do not take more than 1200 mg of ibuprofen per day,” he continued. “Naproxen is probably the safest NSAID and we can take up to 500 mg a day. Diclofenac is the riskiest NSAID and should be avoided by patients with cardiovascular disease and the general population. Safer drugs are available that have similar painkilling effects so there is no reason to use diclofenac.”
Did not do good on naproxen (understatement).
 

Gingergrrl

Senior Member
Messages
16,171
Well that was 20 years ago and I'm not dead yet from Vicodin but I did have Takotsubo Cardiomyopathy about a year ago which is not from clogged arteries, it isn't as rare as first thought but little is known about it. I can tell you that my left ventricle is still enlarged.

@PNR2008 I'd been thinking of you and wondering how you were doing since the Takotsubo episode. Am sorry to hear your left ventricle is still enlarged and you are still suffering from it.

Well guess who gets crap at the ER for taking Vicodin? The Dr. said he'd had to report me, To my Mom? No to my state.

Why did he have to report you? If the Vicodin was legally prescribed to you by your doctor, I don't even see why it is the ER doc's business? What do they have to tell the state?!!! This is beyond insane to me.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
I was talking a LOT of ibuprofen daily (I think twice the over the counter max but I had discussed this with my doctor).
I was taking prescription ibuprofen before it was available over the counter. The standard prescription dose is twice the over-the-counter pills. When you (and I) were taking it only a few day/month, I don't think it is anything to be concerned about.
 

valentinelynx

Senior Member
Messages
1,310
Location
Tucson
2400 mg of ibuprofen per day destroyed my small intestine. Turns out small intestine damage is more common with NSAIDs than gastritis, just poorly known because it can't be seen on endoscopy. I had the PillCam study, in which you swallow a pill sized camera that takes photos and wirelessly sends them to a recorder. I had the study because of pretty bad anemia, and negative endoscopy from above and below. My small bowel was full of ulcers and scars that GI doc said was classic for NSAID enteropathy. In addition to anemia, I have low serum protein (despite consuming enormous amounts of daily protein), as it seeps out of the damaged small intestine.

Very few doctors know about NSAID enteropathy. In my work I see patients all the time with anemia. I ask them why they have anemia and they say, "I don't know." Chances are it's from NSAID damage to the small bowel.

Current politics would have you believe that NSAIDs are safer than opioids for pain. 'Taint so, I'm afraid. I was happy to cut my opioid use in half when I found that ibuprofen helped so much. Now I can't even take Celebrex, because it causes my small intestine to bleed, too.
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
2400 mg of ibuprofen per day destroyed my small intestine
I'm so sorry to hear that. How long were you on it?

I did not know about intestinal problems. Do you know whether this problem applies to most/all NSAIDs? (eg, the stronger prescription ones, like ketorolac?)

I think I was only worried about stomach problems when I was on that high dosage ibuprofen, taken every day for several years (3-4?), due to my endometriosis pain.

The reason I was on high daily ibuprofen for years was because it took me a while to research endometriosis treatments, then decide on surgery, choose a surgeon, figure out how endometriosis surgery might interact with my ME/CFS symptoms, etc. And this was all happening while I was still trying to keep my job (often cycling between a medical leave of absence to get some rest and then returning to work either part time or full time-what can I say, I was in denial).

Fortunately I seem to have avoided any problems from all that ibuprofen and ketorolac that I took (in spite of high doses & bending the rules to take more ketorolac than I should).

In hindsight, as someone who has orthostatic intolerance, I think that high dosage of ibuprofen may have had some positive side effects. (FYI, I'm not saying that these positives would necessarily outweigh the risks)

Quote from article linked in the first post (bolding is mine) -
The researchers speculated that the results could be explained by the effect of the drugs on the cardiovascular system, as they influence platelet aggregation and the formation of blood clots. They may also cause arteries to constrict, increase fluid retention and raise blood pressure.

Hmm, it causes blood vessel constriction? Fluid retention? Increase in blood pressure? You say that like it's a bad thing!

More seriously, I took a nose dive after my endometriosis surgery. I filed for long term disability after that. There were a lot of reasons - it's always hard to recover from surgery - but I wonder if one small factor is that I was no longer taking large, daily doses of ibuprofen which were helping in small way with maintaining my blood pressure?

Just a guess, I have no real clue.
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
I was taking prescription ibuprofen before it was available over the counter. The standard prescription dose is twice the over-the-counter pills. When you (and I) were taking it only a few day/month, I don't think it is anything to be concerned about.
True, but I was taking prescription dose ibuprofen daily for years. Plus ketorolac 6-7 days a month (supposed to take that no more than 5 days in a row) while I had my period and the pain got even worse.

I think the confusion is that unlike what most people think (pain only comes during your period) my endometriosis slowly got worse and worse until I was in daily pain. Not just pain during my period but pain every single day.

On top of that, the pain got even worse during my period (screaming on the bathroom floor pain). I switched to prescription NSAID ketorolac (Toradol) for "5" days (really 6-7). After my period ended then I switched back to 2400 mg daily ibuprofen (and I may have cheated on that, too, I don't remember).

I will end on a positive note and say this - In spite of losing my job, and having to file for long term disability afterwards, having surgery to treat the endometriosis was the best decision of my life. (excision of abnormal endo tissue, not full hysterectomy) No matter what happens I am SO GLAD that I don't have that level of pain any more.
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Damage to the gastrointestinal lining is why COX2 inhibitors were created. The idea is that they do not typically target the version of COX found in the gastrointestinal tract. I wonder if that applies if you have leaky gut. In that case even COX2 inhibitors will do damage by damaging tissues behind the lining. This is speculative of course, but I think its a valid question.

The problem is that decreased damage to the gut is why the doctors were happy to use more effective doses of COX2 NSAIDs. They worked better. Yet that means they had an even bigger impact on eicosanoid synthesis. This will derange all tissues at the cellular level.

If I recall correctly, Naproxen is often favoured because on average it increases life expectancy, whereas most NSAIDs decrease life expectancy. So usually its a better choice. The problem is the patients who are not average patients.

In the long run I think this evidence based approach will die, as its based on a population response, and I think that with advancing technology medicine will move to a personalized approach, though it may take decades more of technological advances before this becomes fully feasible.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
True, but I was taking prescription dose ibuprofen daily for years.

I think the confusion is that unlike what most people think (pain only comes during your period) my endometriosis slowly got worse and worse until I was in daily pain.
Sorry, my befogged brain thought you were taking the ibuprofen 6-7 days/month. This did confuse me. My sister had endometriosis and she had pain every day. :ill:
 

ahimsa

ahimsa_pdx on twitter
Messages
1,921
Sorry, my befogged brain thought you were taking the ibuprofen 6-7 days/month. This did confuse me. My sister had endometriosis and she had pain every day. :ill:
No problem, it's easy to get confused (I misread things on the forum all the time).

Sorry to hear about your sister.
 

valentinelynx

Senior Member
Messages
1,310
Location
Tucson
Damage to the gastrointestinal lining is why COX2 inhibitors were created. The idea is that they do not typically target the version of COX found in the gastrointestinal tract.

Unfortunately, this only appears to apply to the stomach. Prostaglandins protect the stomach from stomach acid. Cox 1 inhibition decreases prostaglandins: gastritis and ulcers can result. The small intestine damage appears to be a direct toxicity from exposure to NSAIDs. Studies are equivocal on whether Cox2 inhibitors are less likely to cause NSAID enteropathy. In one study celecoxib did not but in another, etoricoxib (which is a very selective Cox 2 inhibitor, more so than celecoxib) did cause the enteropathy. Personally, my gut started bleeding again (shown by my developing severe anemia again) when I starting taking regular celecoxib (Celebrex) so I'm pretty sure that Cox 2 inhibitors are a no go as well as far as the small intestine goes.

IV NSAIDs (e.g. ketorolac) probably will not cause this problem, if it is in fact a direct toxicity, but they can cause severe gastritis through prostaglandin inhibition. I'm not aware of any IV Cox-2 inhibitors as of yet.
 

valentinelynx

Senior Member
Messages
1,310
Location
Tucson
I'm so sorry to hear that. How long were you on it?

I did not know about intestinal problems. Do you know whether this problem applies to most/all NSAIDs? (eg, the stronger prescription ones, like ketorolac?)

@ahimsa: I think it was about 1 1/2 years I took the ibuprofen at that level, until the GI doc diagnosed me with the NSAID enteropathy. I started taking it when my finger joints swelled up after I started antibiotics for tick borne disease. It helped so much with my joint pain that I kept on it.

The problem probably does apply to most/all NSAIDs are that taken orally. It appears to be a direct toxicity from contact of the drug with the intestinal mucosa. One study found that celecoxib (Celebrex) did not cause it, but another found that etoricoxib (a very selective Cox-2 inhibitor, meaning it hits almost only Cox-2 receptors not Cox 1) did cause NSAID enteropathy. Personally, I got quite anemic and had blood in my stool (on Hemoccult test) when I started taking Celebrex regularly, so I'm pretty sure it's just as guilty. Depending on what you read, some publications say that aspirin doesn't cause this problem, while others demonstrate that it does. There are studies showing that a single dose of NSAID increases the permeability of the small bowel mucosa.

IV NSAIDs (the only one I know of is ketorolac) probably won't cause this problem, if it is in fact due to direct toxicity to the mucosa. The GI risk with ketorolac is for gastritis: that's why you're not supposed to take it for more than 5 days in a row. Taking proton pump inhibitors can help prevent this.

However, PPIs may actually make NSAID enteropathy with oral NSAIDs worse! This may have to do with the effect of PPIs on the gut microbiome. Intriguingly one of the most effective things found in research for preventing NSAID enteropathy is metronidazole (an antibiotic).

I discovered that there is a drug in the pipeline that combines ibuprofen with phosphatidylcholine that apparently works to prevent the enteropathy. So I've started taking phosphatidylcholine (a nutritional supplement), hoping it will help heal my gut. I think it may be working: my albumin levels seem to be rising, so perhaps I'm not leaking as much protein out of my gut!
 

RogerBlack

Senior Member
Messages
902
IV NSAIDs (e.g. ketorolac) probably will not cause this problem, if it is in fact a direct toxicity, but they can cause severe gastritis through prostaglandin inhibition. I'm not aware of any IV Cox-2 inhibitors as of yet.

Gel form skin-applied ibuprofen and other painkillers exist. I wonder if this would have any less effect.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Unfortunately, this only appears to apply to the stomach.
I am still unsure if this is right for the same reason as I stated before. I suspect the NSAID penetrates deeper than the gut lining at too high a concentration, and that is where the damage happens. Its only a suspicion though. The intestines etc. are where nutrient transfer occurs, and NSAIDs are small molecules. Now while I think there is damage to the entire body from them, that would most likely be higher in the upper intestine.

If my suspicions are right than intestinal damage should be less (but not non-existant) for sustained released inhibitor, does anyone know if this is shown to not be the case?

Prostaglandins do not protect the stomach from acid. They are integral to gut lining repair, including the stomach. Damage occurs all the time, and the gut repairs itself. Blocking prostaglandin synthesis prevents this from happening fast enough, leading to damage, bleeding and ulcers. The damage is regular damage, its the repair mechanism that is faulty. Once the stomach lining etc. is compromised the stomach secretions, not just acid, can directly make contact with exposed flesh.

I would also want to know the tissue distribution of COX2 through the entire gut.

COX2 inhibitors were regarded as safer, so allowable doses were increased. I don't think that is a good idea. I think that is the core of the problem.

There is also a risk to the liver and a few other organs such as kidneys.

Now there are some NSAIDs that have good side effects too, such as the blood thinning and anti-inflammatory effects of aspirin, not all of which appears to be due to prostaglandin inhibition.

Nor is it just prostaglandins. All eicosanoid hormones can be inhibited. These act at the cell and tissue level, so this will disrupt all regulation of those hormones and hence cell and tissue function.

Anyone who is salicylate sensitive or glutathione depleted is at increased risk, as are vegetarians.