Analgesic question --- Celebrex, Vioxx

What is so revolutionary about Celebrex, Vioxx and other “new” pain medications? My primitive understanding is that, for instance, ibuprofen inhibits 2 different enzymes, COX1 and COX2, even though only one of those is pain-related. And that the other enzyme is for stomach lining repair purposes. Thus Advil or Motrin or whatever brand of ibuprofen you’re taking is effective against pain but “turns off”, for a time at least, a salutary stomach repair enzyme. Thus you might experience tummy troubles and, if used too much, even noticeable stomach bleeding.

Is my primitive understanding close? Is Celebrex “the bomb”? Is there any drawback to Celebrex not shared by other analgesics like ibuprofen or acetaminophen? Have I asked enough sub-questions in this “question”?

Probably because pain/inflammation is so common, hence the myriad NSAID drugs. Acetaminophen is a different chemical family-analgesic, but not anti-inflammatory. So it has no gastric irritation.

These drugs are common for the same reason as anti-depressants- so many patients & no one pefect drug.

Your understanding is correct. Older analgesics inhibited both enzymes, because it was only recently discovered that there were actually two different enzymes involved. As soon as that discovery was made, everyone rushed to find drugs that inhibited just the one form so it wouldn’t have the nasty side effects.

I’ve never used them myself, and I don’t know what the problems are. I’m sure if you went to the manufacturers’ websites, they’d have the side-effects listed.

When taken at the recommended dosage, COX-2 inhibitors produced less stomach upset and fewer GI complaints than COX-1 & -2 inhibtors (aspirin, ibuprofen). However, since their introduction to the market, these drugs have received knocks for (1) causing very severe GI problems, including bleeding, in those patients who DO get side effects; (2) being less effective than OTC NSAIDS for pain and inflammation when used at the recommended dosage.

Many observers are now crediting the dosage, rather than any characteristic of the drug, for the benefits seen in clinical testing.

Thanks, folks. Nametag, that is very disheartening because I have to take something regularly for a nerve-pinching problem I have developed from working at the computer at my bank all day. I’ve done all the posture adjustments one person possibly could but extended computer use still causes “golfer’s elbow” in whichever arm I use the mouse with. And, sadly, extended computer use is the very nature of my job.

I am applying to grad school for fall 2004 and the main impetus is to get a break from this physical deterioration. Yes, more education is always a good thing, but I am pretty happy with my job and sad that I have to get the heck out of there. The pay, while not great, is decent and the hours and working environment are great. But you only live once and I’m a 32 year old who feels there’ll be plenty of time to physically deteriorate later on in life. Ibuprofen helped me a LOT…one Advil tab at each meal was doing wonders. But the stomach problems did creep along and I just don’t like taking 400-600 mg or whatnot a day. I appreciate the info, folks!!:slight_smile:

Well, there’s no harm in trying; Celebrex and Vioxx do work as advertised in many people – maybe even most people. I was just pointing out that they’re not quite as miraculous as advertised.

Oh yeah, it has worked pretty well so far, and no tummy troubles yet. Wanted to know more about it, though, and now I do.

Celebrex and Vioxx cause marginally less GI complaints than traditional NSAIDs. They were introduced with a shower of hype but really aren’t the bomb. They are a good first choice for arthritis for elderly people with a drug plan. I find Naproxen much more effective, for more people, for inflammatory pain.

Hey bromells,

I tried to post this last night, but the site went down. Better late than never:

When cyclooxygenase-2 (COX-2) was discovered in the early 1990s, a dogma emerged. COX-1 was constitutively expressed in many tissues, while COX-2 expression was usually only detected under inflammatory conditions. For some reason, this made some scientists automatically believe that COX-1=good and COX-2=bad. This is an incorrect belief. For example, acetylated COX-2 produces lipoxin A4, which protects the gastric mucosa.

However, big pharma saw the money that could be made from the dogma, and immediately began searching for selective COX-2 inhibitors. Now we have Pharmacia’s Celebrex and Merck’s Vioxx, among others. These drugs were approved by the FDA without sufficient clinical testing, and have done staggeringly well. Unfortunately, both Pharmacia and Merck lied by omission when they released their toxicity data.

Pharmacia:

  1. They found that Celebrex had a better gastric toxicity profile than two other non-selective NSAIDs over a period of six months. However, the study was continued for one full year, at which point there was no difference in the risk of ulcer complications between Celebrex and diclofenac. Pharmacia chose not to release this data.
  2. In addition, AFTER the clinical trials, Pharmacia went back and eliminated the data stemming from patients concurrently taking low-dose aspirin, as they demonstrated very high levels of adverse GI events. Pharmacia chose not to release this data.
    The World Health Organization has since forced Pharmacia to disclose the data from these two points (page 6).

Merck:

  1. Patients taking Vioxx had significantly higher rates of developing myocardial infarction or other serious thrombotic events than patients taking a conventional NSAID. Merck chose not to release this data. Here’s the low-down (page 13).

Talk to your doctor. Choose wisely. If you’re interested in knowing any more specific details about the molecular side of this issue, I’d be more than happy to discuss them!

-Apoptosis

To each his own, but I personally have had about an 80% improvement in my quality of life since starting on Celebrex for my back/shoulder pain. (I had a major spinal fusion and have a lot of pain from it, sciatica, etc) Naproxen did nothing for me, Ibuprofen ate my stomach, Vioxx didn’t work, but Celebrex has been a life saver. So results definately do vary.

I’m not saying results don’t vary. But I see a lot of people with various types of pain. And I’ve just not been that impressed with Celebrex and Vioxx. Lots of people swear by them. Lots of people get high blood pressure or their stomachs eaten from any of these medicines. And I worry about the loss of cardioprotection which seems to come with some of the newer medicines.

Vioxx and Celebrex do have their place, as does Mobicox, ASA, ibuprofen, etc. But the drug companies put a lot of money into promoting these new medicines, and I’ve seen my share of GI bleeds due to them.

Hey Dr_Paprika,

And we’re not just talking about loss of cardioprotection. As I cited above, Vioxx increases your risk of suffering serious thrombotic events. This was to be expected: COX-2 is the main source of prostacyclin in the circulation. Knocking out COX-2 leads to a shift toward thromboxane-A2 production via COX-1 from platelets. Result: thrombosis.

-Apoptosis

I’d agree. Thromboxane A2 enhances platelet aggregation, PGI2 (prostacyclin) decreases it. Aspirin, especially at low doses, inhibits thromboxane production by inhibiting cyclo-oxygenase non-specifically.

Well, for a person who has tried all of the abovementioned drugs except Celebrex and has never had any side effects from any of them, anecdotally acetominophen and naproxen do diddly-squat for me, ibuprofen helps if the pain is mild but does diddly-squat if it’s bad, and Vioxx rocks! (25 mg usually does the trick). But then I’m young and basically healthy (no gastric, liver, or kidney issues), and my only issue for which I use any of the above on a regular basis is post-traumatic arthritis in one ankle (and associated soft tissue issues).