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COX-2

COX-2 implications and gastric mucosal integrity, ulcer healing – (08-23-01)

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COX-2 implications and gastric mucosal integrity, ulcer healing

This is an informative review article on the new wonder-drug arthritis meds, and the concept that maybe they are not so friendly to the gastric mucosa as they were marketed to be. Recently this class of drugs has also come under fire from the cardiology sector. Remember that, just like nature, there are no “wonder drugs.” This applies even more to science’s mutation of natural compounds. This class of drugs hit the ground running and created quite a profit for the two drug companies producing them. Unfortunately, it appears that most of the patients taking these drugs are guinea pigs when it comes to identifying the long term side effects and efficacy.

Gut — Abstracts: HALTER et al. 49 (3): 443

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COX-2 Expressed at High Levels in Pancreatic Tumors – (02-12-01)

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COX-2 Expressed at High Levels in Pancreatic Tumors

This study demonstrated high levels of COX-2 in several types of pancreatic tumors, and the addition of COX-2 inhibitors slowed the growth of the tumors. Now, before we jump up and down at this discovery and throw lost of research money into the study of COX-2 inhibitors and pancreatic cancer, we must remember Dr. Gonzalez’s work using high levels of pancreatic enzymes, detoxification, coffee enemas and other healthy lifestyle changes. Normal survival for pancreatic cancer rarely exceeds 19 months. Period. In a small study, Dr. Gonzalez achieved 45% survival rate at 2 yrs, with four of eleven patients still surviving.

Entrez-PubMed

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Cancer 2001;91:333-338 Over half of pancreatic tumors express cyclooxygenase-2 (COX-2), Japanese researchers report. In addition, COX-2 inhibitors can inhibit the growth of pancreatic cancer cells in vitro. The researchers also investigated the effect of the COX-2 inhibitors aspirin and etodolac on the growth of four pancreatic cancer cell lines, of which two expressed COX-2 weakly and two expressed the protein strongly. Both drugs inhibited the growth of the cells. “Although the reason remains unclear, there was a negative correlation between the intensity of COX-2 expression and the 50% inhibitory concentration of aspirin but not of etodolac,” the authors write. They conclude that COX inhibitors are “possible preventive agents against pancreatic neoplasms.”

Pondering Vioxx: Easier on Stomach, Harder on Heart? – (06-25-01)

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Pondering Vioxx: Easier on Stomach, Harder on Heart?

Remember one thing in medicine–there is no miracle cure and anything that is advertised as the best thing since slice whole grain bread-you can bet there’s some major side effects. So, when it comes to joint pain relievers, you can take one of the new COX-2 inhibitors and maybe have less chance of death from bleeding ulcers, but you may die of a fatal MI instead. Some choice, huh? How about exercise, chiropractic care, glucosamine, chondroitin, MSM instead?

Joint Letter 7(4):37,44-46, 2001 Pharmaceutical giants Pharmacia and Merck recently petitioned the U.S. Food and Drug Administration (FDA) to relax gastrointestinal (GI) safety warnings on the labels of their respective COX-2 inhibitors. Last month, we reported on Pharmacia’s submission for celecoxib (Celebrex). This month, we examine Merck’s request for rofecoxib (Vioxx). As of press time, the FDA had not issued a final decision.Vioxx is easier on the stomach than generic naproxen. But it may be harder on the heart, according to recent briefings presented to the U.S. Food and Drug Administration’s Arthritis Advisory Committee.On February 8, representatives from Merck presented data to the advisory committee from Merck’s huge randomized VIGOR trial, which compared Vioxx to the nonsteroidal anti-inflammatory drug (NSAID) naproxen in 8076 patients with rheumatoid arthritis (RA). The advisory committee also heard from the FDA’s own in-house analysts, who offered interpretations of the VIGOR data that sometimes conflicted with Merck’s. After factoring in all the safety data on GI benefits and cardiovascular risks, the FDA’s medical officers concluded that the highly touted COX-2 inhibitor was no safer than naproxen. They recommended the Vioxx label be modified to include more cautions, rather than fewer. “To a patient it, doesn’t matter whether you end up in an intensive care unit with a big GI bleed or whether you end up in an intensive care unit with a myocardial infarction,” noted advisory committee member Steven Nissen, MD, reflecting this concern. “They are both pretty bad things to have happen.”

Topical Solution for Osteoarthritis May Challenge COX-2 Inhibitors – (03-18-01)

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Topical Solution for Osteoarthritis May Challenge COX-2 Inhibitors

We are starting to see a large number of “miracle” creams for arthritis hitting the market. Remembering back to the old Ben-gay type preparations, these were purely skin irritants designed to flood the spinal cord with “touch” sensations and prevent pain transmissions for reaching the spinal cord first. New preparations have included many additional topicals ranging from glucosamine/chondroitin to capsaicin. The studies on these types of therapies, to my knowledge, are still scarce. However, the safety of many of these topicals is very good and may warrant a personal clinical trial.

(article) British biotechnology firm Provalis plans to launch its novel topical osteoarthritis solution Pennsaid in the UK this month, saying the product will compete with all nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors. The UK is the first market for the new product. Provalis has acquired from Canadian firm Dimethaid research the right to sell the compound in the UK and Ireland. Provalis chief executive Dr. Phil Gould told a news conference in London that Pennsaid had been approved for first-line treatment of osteoarthritis by the UK’s Medicines Control Agency and would be approved in the rest of Europe under the mutual recognition procedure. Dimethaid is seeking distributors for the other European countries and has signed a deal with Johnson & Johnson for marketing in the United States. Dimethaid’s technology uses the cell’s tubule system to deliver drugs cell-to-cell. As a result, localised conditions, such as osteoarthritis, can be treated while limiting the body’s absorption of the medication. Dr. Gould said that comparative data showed that pain relief is as least as good with Pennsaid as with the COX-2 inhibitor celecoxib and oral formulations of the NSAIDs diclofenac and naproxen.

Red Wine, Black Tea Polyphenols Modulate Expression of COX-2 – (06-10-02)

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Red Wine, Black Tea Polyphenols Modulate Expression of COX-2

Geez–billions of dollars spent on developing and creating the market for a selective COX-2 inhibitor (quite an interesting tale if you follow Mansanto’s “public health” info on the dangers of non-selective COX inhibitors) when we’ve had several compounds that seem to do the same thing already in own kitchen cabinets. Oops…I forgot that you can’t patent and make gobs of money off of wine and tea. This study mainly focuses on the potential anti-cancer abilities of inhibiting certain enzyme systems in the GI tract.

Nutrition.org — Abstracts: Luceri et al. 132 (6): 1376

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Gastrointestinal bleeding after the introduction of COX 2 inhibitors – (06-18-04)

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Gastrointestinal bleeding after the introduction of COX 2 inhibitors: ecological study

This is a very interesting article. When the COX-2 selective inhibitors were first released, I was seeing many patients come in that were prescribed this class of drugs, most inappropriately (was only supposed to be used in patients at high risk of GI complications). However, the number has dropped off to almost zero. This once blockbuster class of drugs seems to be falling to research that is finally showing that it is not all that effective as a pain med, and it’s side effect profile is really nothing to brag about, either. And all this coupled with the fact that this is a very expensive class of drugs compared to other NSAIDs.

This article notes that, with the 41% increase in NSAID use (due entirely to the increased use of COX-2 inhbitors), a 10% increase in hospitalization rates for upper GI bleeds was seen. Sell your Pharmacia stock.

bmj.com Mamdani et al. 328 (7453): 1415 –

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USE OF COX-2 AGAINST KNOWN DAMAGES OF NSAIDS – (05-29-03)

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Adverse renal effects of anti-inflammatory agents: evaluation of selective and nonselective cyclooxygenase inhibitors.

With the sharp increase in COX-2 use such as Celebrex and Vioxx (most of this use being inappropriate for its indications), we really need to evaluate the selective COX-2 inhibitors against other known damages from NSAIDs. Here we see that the COX-2 inhibitors are just as dangerous to the kidneys as traditional NSAIDs. And much more expensive. Hey–just use the cheaper NSAIDs and save the extra money for that kidney transplant!!

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LACK OF PROTECTION WITH REGARDS TO ANTIDEPRESSANTS AND CHILDREN – (10-20-04)

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Failing the Public Health — Rofecoxib, Merck, and the FDA

By now everyone has heard that Merck pulled it’s blockbuster drug from the market. Not a big surprise, since it was mentioned here at least 3 years ago (October 2001, Research Updates) that there were cardiac issues with the selective COX-2 inhibitors. There was clearly a failure of the FDA to protect the public in this situation. But we have also recently seen the same lack of protection with regards to antidepressants and children. It is the almighty dollar that rules here, but the general public still believes that the FDA is really out there with our best interests at heart. So, they pull ephedra, possibly linked to a handful of deaths when used INAPPROPRIATELY, but take years to pull off drugs, used APPROPRIATELY, off the market.

NEJM — Failing the Public Health — Rofecoxib, Merck, and the FDA

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