+ Cox 2 Inihibitors/NSAIDS Are Not Effective
The Risks Outweigh The Benefits
How NSAIDs such as: (Ibuprofen, Aspirin, Naproxen, Vioxx, Bextra, Celebrex) Do More Harm Than Good.

The Hippocratic Oath requires physicians to “First, do no harm,” but that has not prevented medication mistakes from injuring well over 1.5 million Americans annually. That’s according to a report called Preventing Medication Errors from the Institute of Medicine of the National Academies

The sheer volume of medications is a big part of the problem – with 10,000 prescription drugs and 300,000 over-the-counter products on the market, no one could possibly memorize the different usage and dosage instructions for all of them. Even computerized databases cannot keep up, especially when you consider the potential for interactions between drugs.

Did you know that many of the common over the counter drugs used to treat soreness and minor aches and pains, can actually cause destruction of your cartilage, stomach and digestive tract.

What Are COX2 (COX-2) Inhibitors And How Do They Work?
COX-2 inhibitors are drugs such as Vioxx, Celebrex and Bextra. To understand COX-2 (COX2) Inhibitors, you first have to understand COX-1 (COX1) and what its role in the body is. Regular NSAIDS (mostly COX-1 and a bit of COX-2 Inhibitors) work by inhibiting the production of prostaglandins (PGs). Prostaglandins are fatty-acid derivatives located all over your body that are well known for their inflammation and immune response effects.

However, they also have many different functions in the body. A scientific list would read as such: PG’s are involved in as diverse normal processes as ovulation, blood clotting, renal function, wound healing, vasomotor tone, platelet aggregation, differentiation of immune cells, nerve growth, bone metabolism, and initiation of labor. Pretty essential to your body, wouldn’t you say? The key point here is that shutting down PG's does more than just shut down your pain - it impacts your entire body too!

If you are familiar with the fact that when you are using drugs such as aspirin, your blood thins and you bruise easier, that is a “side effect” of the COX-1 inhibitor. In the above list, that would fall under the blood clotting category. Remember, COX-1 inhibitors work by inhibiting PG’s. Due to the acidity of the stomach, the cells of your stomach are normally replaced very quickly, within a few days. One of the major roles of PG’s is to keep the lining of the stomach intact, and when your PG system is disrupted (say by taking COX-1 drugs like many NSAIDS) stomach irritation, digestive tract problems and even intestinal or stomach bleeding and ultimately death could occur. In fact, according to The New England Journal of Medicine, over 103,000 hospitalizations and 16,500 deaths annually are caused by complications from NSAID drugs. Remember, NSAIDS are common pain relievers such as aspirin! Aspirin makes your stomach bleed! Surely COX-2 drugs, being designed to be more specific would not have these side effects? That was the original thinking, anyway...

COX-2 inhibitors were discovered later, and were presumed to be a “healthier, more targeted” way of treating the soreness – without the side effects. This makes sense as COX-2 is found more commonly in inflammatory and immune cells than COX-1 drugs, which exist throughout the body. Unfortunately, this would prove to be far, far from the truth. While COX-2 is more specific to soreness, the side effects can be far worse than COX-1 drugs. Vioxx, Bextra and Celebrex are all COX-2 drugs.

The side effects of COX-1 drugs are pretty terrible. It is estimated that 25% experience some kind of side effect and 5% develop SERIOUS health consequences such as GI (stomach) bleeding, acute renal failure, or worse. The New England Journal of Medicine reports that “anti-inflammatory drugs (prescription and over-the-counter, which include Advil®, Motrin®, Aleve®, Ordus®, Aspirin, and over 20 others) alone cause over 16,500 deaths and over 103,000 hospitalizations per year in the US”, according to a review article published in the New England Journal of Medicine1.

You can see why researchers would believe there was a clear cut and dry line between COX-1 and COX-2. The message was clear: research (and get patents for) drugs that actually inhibited only COX-2 and you would have a blockbuster drug on your hands. The sad part was that the people who took COX-2 drugs were the ones to suffer. Over the counter drugs such as Ibuprofen and Naproxen work to inhibit COX-1 and COX-2. Aspirin works more on COX-1. Some others such as diclofenac work primarily on COX-2 but also affect COX-1. However, even “selective” COX-2 inhibitors are not that selective. At therapeutic dosages, they inhibit enough COX-1 to potentially cause the same stomach toxicity and other associated problems as regular COX-1 drugs.

Not to the exact same extent but more than enough to do damage. According to a review article published in the New England Journal of Medicine, “anti-inflammatory drugs (prescription and over-the-counter [NSAIDS and COX-2 drugs], which include Advil®, Motrin®, Aleve®, Ordus®, Aspirin, and over 20 others) alone cause over 16,500 deaths and over 103,000 hospitalizations per year in the US.” In development are other “newer aspirins” that may prove to ACTUALLY be more selective for COX-2 than COX-1, but in the mean time – despite claims of being “selective” – the current COX-2’s such as Vioxx® (rofecoxib) or Celebrex® (celecoxib) are simply not selective enough, not to mention some of their potentially horrible side effects and the associated lawsuits that have been filed (and won) due to side effects such as heart attacks, stroke and blood clots.

Why are NSAIDs sometimes Fatal?
There are several reasons for the fatalities of NSAIDS. Let’s first start with the early generation NSAIDS. The early NSAIDS (non steroidal anti-inflammatory drugs) worked a little bit on both COX pathways, COX-1 and COX-2. Both of these pathways regulate (in part) inflammation.

The NSAIDS highly target the inhibition of COX-1 (an enzyme called cyclooxygenase) and largely ignore COX-2. This means they work to mask pain but they have other unintended side effects because COX-1 controls certain functions of the stomach, kidney, and platelets.

The COX-1 enzyme (that NSAIDS block) is present in most parts of the body, which is why when you inhibit COX-1 you have these other "unintended" side effects, like stomach bleeding, ulcers and other effects that can over time lead to very serious conditions like heart attacks or strokes - or even death. With NSAIDS, you are offsetting several body systems at once instead of really targeting the one body system responsible for inflammation. Think of COX-1 as a shotgun approach whereas COX-2 in “theory” is much more of a targeted attack.

Along came "Better" COX-2 Drugs
The development of COX-2 drugs was a breakthrough for the pharmaceutical industry. Now they had the ability to patent and market newer drugs such as Vioxx® or Celebrex® and joint pain drugs quickly rose to become some of the best drug sellers of all time. (They still are). In theory, the targeted effects of COX-2 inhibition would solve all of the problems of NSAIDS. All of the benefits of COX-1 without the nasty side effects. Their only purported downside is they are very expensive, $200 or more a MONTH in some cases.

Compare this to $30 for other more effective therapies such as glucosamine. What many doctors do not tell you or simply gloss over is that other downsides of COX-2 include the risk of sudden heart attack, stroke or blood clots, without preexisting coronary heart disease. That's right, otherwise healthy individuals. COX-2 drugs work great for relieving pain but they can and do kill people on a regular basis. Many doctors are wising up to the disastrous side effects of these drugs and have stopped prescribing them.

Other, less informed doctors simply hear what drug reps tell them to prescribe for certain conditions and they dole out drugs based on what they “should” be giving out. Fortunately many doctors are wising up and realizing that COX-2 inhibitors have a cause and effect method of action, and this action is what proves to be fatal in many people who take COX-2 drugs.

Checks and Balances - Unbalanced!
The body has thousands of systems of checks and balances, designed to prevent extremes or unbalances. Just think of how many systems are working right now to maintain your body with optimal levels of water, oxygen, glucose and many more chemicals on a second by second basis. The COX-2 pathway operates in much the same way. When you inhibit COX-2 enzymes, you mask inflammation and pain, bypassing the COX-1 side effects. Pretty good so far, right? The only downside is COX-2 is in a way like COX-1. COX-2 also mediates BLOOD CLOTTING. This is where COX-2 can be fatal. When you get a cut or experience minor trauma you sever blood vessels (from small capillaries in the skin all the way to a small tears in the largest blood vessel of them all, your aorta). This bleeding cannot go on without being stopped or you would eventually bleed to death.

The body (within seconds) releases a clotting agent that binds blood together and causes a clot to form. This clotting agent stops the initial blood flow and “plugs the hole." About 2 to 3 minutes later, the body is able to start a process that stops this blood clotting. Both of these processes are started at the same time but the first one finishes within seconds and the second one takes 2 to 3 minutes. The second 2 to 3 minute process is what is called a rate limiting process. This process is what STOPS the blood from clotting so that once the damage has been patched, the clotting can stop. COX-2 disrupts this process, allowing clotting to continue far past when it should. As you can imagine, clotting inside the body can be fatal. Get a clot in your heart and you have a heart attack.

Get one in your brain and you have a stroke. But did we mention that COX-2 drugs really do work great for covering up joint pain! And to be sure, not everybody is going to experience trauma to their blood vessels on a regular basis (this is why COX-2 drugs are still on the market), but as we age and as a result of simply living, small imperfections become more and more probable, as plaque and small clots form and the blood vessels become less elastic and more prone to tearing. Fortunately, newer technologies have been discovered but remain somewhat unknown, mainly because it cannot be patented and thus - there is little profit for big pharmaceutical companies.