Ask a pharmacist: Which NSAID should I take? Part I

I got a few real-life questions for a pharmacist last week, but you know what? They were all about vitamins. I didn't want to talk about vitamins again. So I found an imaginary friend question I liked better (although I will get to those questions. Except maybe the vitamin E one, way to pick a tough topic Termite!) This question is about NSAIDs - those helpful pain and inflammation killers that can be so confusing.

If you run, you probably take NSAIDS for pain and swelling. Actually if you have ever had pain, fever, cramps, or swelling you have probably taken NSAIDS. NSAIDS (non-steroidal antiinflammatory drugs) are agents that reduce pain and inflammation by modifying the COX enzyme pathway. These enzymes facilitate the production of prostaglandins which cause pain, inflammation, and fever. The name "NSAIDS" was chosen ages ago to distinguish them from steroids, which are a completely unrelated type of antiinflammatory.
To understand how NSAIDS work, let's review a little pharmacology.

It's easy, I promise.

First, let's talk about what happens when you are injured. Let's say you shut your thumb in the door. You're hurt, and your cells are hurt. When the door slams, it squishes your cell membranes, and they release a compound called arachidonic acid (with the help of phospholipase-A, an enzyme). This starts what we call the "COX pathway", your body's antiinflammatory response to injury. Arachidonic acid is broken down by the COX enzymes to create several products:  thromboxane, a compound that causes platelets to adhere to each other and cause clots; prostacyclin, a compound that causes blood vessels to enlarge and prevents platelet clotting; and certain prostaglandins, which cause swelling, pain, uterine cramping, and fever. Now right off the bat you probably wonder why your body responds to injury by making compounds that both CAUSE clotting and PREVENT clotting. It's all part of keeping balance during an injury to make sure your blood can bring the healing cells it needs to the injury sight ... yet you won't bleed to death either. The clotting pathway, however, is complex and goes beyond our scope today. So back to NSAIDS. Anyway, these prostaglandins are useful in healing your body, but they cause uncomfortable effects, too. For example, fever is meant to kill bacteria that might have invaded the sight of injury, but we don't always want to deal with fever. So we take drugs to stop these effects. The enzymes that break arachidonic acid down to the prostaglandins that cause inflammation and fever are COX-1 and COX-2. Since COX-2 is produced at the sight of injury and has these results, this is the enzyme we want to inhibit. However, most NSAIDS also inhibit COX-1. Basically they can't differentiate between the two enzymes, so they inhibit both. The problem with that is that while COX-1 can produce inflammatory prostaglandins, we need it for something else. It is present in our gastrointestinal tract at all times, helping to produce different prostaglandins required to maintain the natural mucosal lining in the stomach. If COX-1 is inhibited, these prostaglandins aren't produced, and the stomach becomes easily damaged and upset. Your lining can bleed, severely even.
It would make sense, then, to try to develop a drug that would just stop COX-2, which is only produced by the body at the site of injury. That would spare some side effects. Scientists tried this, and they succeeded. Remember Vioxx? Vioxx, of all the legal claims and law suits? Yeah, there was a problem with COX-2 selective inhibitors. Studies have shown that COX-2 inhibitors increase the risk of heart attack and stroke. I had a 6-paragraph explanation of why this might be so, but it was beyond boring and the conclusion was..."one of these two mechanisms may be the culprit..." so I cut it out. If you want more info, though, email me!
Of course, COX-1 or COX-2 or whatever, all NSAIDS have certain side effects and risks.Before I talk about specific NSAIDS, I'll review the side effects common to all drugs in the class.
Stomach upset: Any drug that reduces COX-1 upsets the stomach and may cause/allow intestinal bleeding. If you have a history of GI bleeding or take other drugs that can cause GI bleeding or have gastric ulcers, avoid NSAIDS.
Blood thinning:  All NSAIDS thin the blood. If you're on a blood thinner you have to discuss NSAID therapy with your doctor; he may allow it but will monitor you more frequently (I have had a patient die from a massive GI bleed due to self-medicating with over the counter ibuprofen. The combination of thin blood and gastric bleeding actually killed him).
Water retention and increased blood pressure: NSAIDS cause your kidneys to hold on to extra water. This will increase your blood pressure and can worsen heart failure, because your heart is burdened with extra fluid to pump.There is more to this, but it is a dry discourse. If you want more info, again, email me.
Kidney damage: NSAIDS can damage the kidney through several mechanisms; mainly they inhibit prostaglandins that allow vessels in the kidney to expand. The tightened vessels prevent the kidney from processing fluids, and the kidney can shut down and fail.
High potassium: It's all connected: the high blood pressure, water retention, and kidney damage are all linked, and they are linked to increased potassium, too (moral of the story: don't mess with your kidneys!). This is usually only a problem for people who already have problems with electrolyte balance or with their kidneys.
Tinnitus: All NSAIDS, but primarily aspirin, can cause ringing in the ears.
Liver failure: Possible with high doses of all NSAIDS. 
Pregnancy/breastfeeding concerns: You may take NSAIDS while breastfeeding. Do not take while pregnant (date shows increased complications when taken during your third trimester).
Who should not take NSAIDs/ask your doctor: Asthmatics, those with a history of stomach ulcer or GI bleeding, people on blood thinners, people with high blood pressure (even on medication since NSAIDs counteract the effects of certain blood pressure drugs - please talk to your doctor), people with heart failure, those who have a kidney disease.

Are you scared yet? Haha. This post is getting horribly long, so I'll leave you with this background and next time I'll go into the differences between different NSAIDS and which are best for which condition.

A note about sources: these posts are my opinion as a pharmacist and based on my training. If I have any fact-checking to do, I generally do it from a variety of reliable sources. If I ever directly use a study or some data, I will reference it. So far these have been too general to require that.