There are two cyclo-oxygenase enzymes, one predominating at sites of inflammation (COX-2) and one constitutively expressed in the gastrointestinal tract (COX-1).
By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract.
Pain from inflammation, involves the enzyme cyclooxygenase (COX).
COX is an enzyme that forms prostanoids―prostaglandins, prostacyclins, and thromboxanes―which are all responsible for the inflammatory response.
Nonsteroidal anti-inflammatory drugs (NSAIDs) affect COX to reduce inflammation.
COX-1 is known to be present in most of the tissues in our bodies.
In the gastrointestinal tract, COX-1 maintains the normal lining of the stomach and intestines, protecting the stomach from the digestive juices.
COX-1 enzyme is also involved in kidney and platelet function.
COX-2, on the other hand, is primarily found at sites of inflammation.
Both COX-1 and COX-2 produce the prostaglandins that contribute to pain, fever, and inflammation, but since COX-1’s primary role is to protect the stomach and intestines and contribute to blood clotting, using drugs that inhibit it can lead to unwanted side effects.
Nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed for arthritis, work by inhibiting prostaglandins.
Traditional NSAIDs, like ibuprofen), aspirin, and naproxen), while effective, can cause gastrointestinal problems including ulcers because they’re non-selective, meaning they inhibit both COX-1 and COX-2.
COX-2 inhibitors Celebrex (celecoxib), Vioxx (rofecoxib), and Bextra (valdecoxib).
Of these, Celebrex is the only COX-2 inhibitor that remains on the market as Vioxx and Bextra were both withdrawn due to the potential for increased risk of heart attack and stroke.
COX-2 inhibitors target pain and inflammation with fewer gastrointestinal side effects.
COX-2 inhibitors may not increase bleeding risk as much as COX-1 inhibitors when used with blood thinners, like warfarin.
The increased risk of heart attack or stroke from using NSAIDs applies to those, with or without heart disease or its risk factors.
For individuals with heart disease or risk factors for heart disease, the risk of heart attack or stroke is higher after using an NSAID than it is for people without the same risk factors.
Being treated with NSAIDs after a first heart attack is associated with a higher risk of death in the first year than those not treated with NSAIDs.
NSAID use increases the risk of heart failure.
Truly selective COX-2 inhibitors have been shown to have no effect on gastric mucosal prostaglandin synthesis, to cause no acute injury, and no chronic ulceration compared to placebo.
The benefits of COX-2 inhibitors may be reduced by aspirin use.
The VIGOR study has suggested the possibility that some NSAIDs, particularly naproxen, may protect against vascular disease compared to COX-2 inhibitors.