Celebrex – for pain and arthritis

Hello friend,

How are you? Holiday time again. Wish you a happy Easter! It’s good to be stepping into spring, isn’t it?

As we get more physically active in spring, we could possibly be exposed to injuries and ….. pain. Pain …. pain …. we’ll be talking about a prominent pain medication today …….. and toward the end of this article ….. well, we’re going to see a painful account of the state of scientific research today ……..

Let’s talk about the drug celecoxib, commonly known in the U.S. under the brand name Celebrex, and in other countries as Celebra, Cobix, Celcoxx, and Selecap. 

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID – pronounced N-sed) – it is a selective COX-2 enzyme inhibitor. I’ll explain that below. Other NSAIDs, which are non-selective, are aspirin, ibuprofen (available as Advil or Motrin in the U.S., Brufen in India) and naproxen (brand name Aleve) – these are available over the counter. Where does the selectivity come from? Let’s look at the mechanism of action of these drugs.

An enzyme in the body called cyclooxygenase (COX) catalyzes the formation of lipid compounds called prostaglandins. There are different kinds of prostaglandins which have a variety of functions all over the body, including regulation of inflammation and sensitizing central nerve cells to pain, as well as contraction and relaxation of gastrointestinal muscles and secretion of stomach acid for the digestion of food.

There are three kinds of COX enzymes. COX-1 is found in most cells at a steady concentration. Prostaglandins that are responsible for the maintenance and protection of the gastrointestinal lining are dependent on COX-1 for their synthesis. COX-2 is induced at sites of inflammation. They are responsible for the synthesis of prostaglandins that cause inflammation and pain. COX-3 (a genetic variant of COX-1), has been shown to be in the brain and may be involved with prostaglandins and headaches – less is known about this enzyme.

The non-selective NSAIDs like aspirin, ibuprofen and naproxen inhibit both COX-1 and COX-2. Celecoxib selectively inhibits COX-2 thirty times more than it inhibits COX-1. Inhibition of COX-2 is beneficial – it reduces inflammation and pain; whereas inhibition of COX-1 can be a problem – it can damage the stomach lining, leading to ulcers in some patients. Selective COX-2 inhibitors, as the name indicates, selectively inhibit COX-2 and thus reduces inflammation and pain, with minimal gastric side-effects.

Prostaglandins have been shown to have a role in vasodilation (blood vessel dilation). When NSAIDs inhibit prostaglandin synthesis, the net effect on the blood vessels is to increase vascular resistance. This can lead to reduced blood perfusion through the kidney filtration apparatus in susceptible individuals. In patients with less than perfect cardiac ventricular function, this can lead to edema (fluid retention) and congestive heart failure (CHF).

COX-2 inhibitors were shown to have more of these kidney and heart side-effects than non-specific NSAIDs. A couple of COX-2 inhibitors, valdecoxib (Bextra) and rofecoxib (Vioxx), that had greater selectivity for COX-2 than celecoxib, were taken off the market because of greater cardiovascular risks than celecoxib. Although several mechanisms of action have been proposed for the greater cardiovascular toxicity of these COX-2 inhibitors, none of them is a complete explanation.

Aspirin, though an NSAID, has an antiplatelet action which prevents formation of blood clots – hence, it is used by at-risk individuals in a low dose (81 mg) daily regimen for cardiovascular health.

Celecoxib, the drug we are discussing today, is orally absorbed with a peak effect between 2 and 4 hours after ingestion. Its elimination half-life is between 6 and 12 hours – this means half of the drug in the body is eliminated in 6 to 12 hours, then half of the amount left in the body is excreted in the following 6 to 12 hours, and so on….

Celecoxib is used to treat rheumatism, osteoarthritis, acute pain and painful menstruation. Under brand name Onsenal, celecoxib is used to treat familial adenomatous polyposis (FAP), a genetic disease characterized by polyps that grow in the large intestine and/or rectum. These polyps have high levels of COX-2. By inhibiting COX-2, celecoxib decreases the growth of the polyps. Onsenal is generally used in conjunction with surgery to treat FAP.

Alright, let’s talk about ……. twenty-one research articles with fabricated data ….. wha .. aa… at? Yup! Favorable results from Celebrex, Bextra and Vioxx as well as Lyrica and Effexor for pain were made up by a prominent anesthesiologist from Springfield, Massachusetts (as reported in Scientific American, March 10, 2009 as well as Wall Street Journal, March 11, 2009 and Boston Globe, March 11, 2009).

Dr. Scott S. Reuben, Professor of Anesthesiology and Pain Medicine at Baystate Medical Center in Springfield, MA, has been influential in estimated billions of dollars of sales of COX-2 inhibitors (according to Paul White, editor, Anesthesia and Analgesia, February 20, 2009). Reuben recently admitted that he did not do any of those studies. He fabricated results, including inventing patients who never existed and forging the names of co-researchers. Scientific American calls him a medical Madoff (a reference to Bernie Madoff who recently perpetrated a 65 billion dollar investor fraud). Of course, his studies have been retracted by the medical journals they were published in.

No, it’s not all bad. Celebrex, Lyrica and Effexor are not expected to be taken off the market. None of Scott Reuben’s studies were part of the application that the manufacturers made to the US FDA or to drug authorities in other countries. They are still effective drugs.

So, why did Reuben lie? To get financial grants from the pharmaceutical companies involved. It has been reported that Reuben acted alone in the fraud.

Human beings, right? The good, the bad, the ugly….. No, we cannot develop a holier-than-thou attitude. Good does not mean perfect. None of us is perfect. However, it’s true that some imperfections in some people affect large populations of people negatively.

Let us hereby resolve to minimize our own imperfections, eh?

Until next week, do take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Advertisements

One Response to “Celebrex – for pain and arthritis”

  1. Doc Says:

    Well done, yet again! Interesting bit about Reuben, eh? The main problem with those bad eggs, is in the effect on the (continuing) decline of the trust of the public towards the health care industry as a whole.

    I cant read the word Celebrex without hearing that god-awful jingle, though.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s


%d bloggers like this: