History
COX-1 is distributed in platelets and gastrointestinal mucosa. Inhibition of COX-1 by aspirin leads to insufficient mucus and bicarbonate in the gastric mucosa, causing ulcer bleeding—[[NSAIDs ulcers]]. This can be prevented by [[misoprostol]].
COX-2 is only distributed at sites of inflammation, and NSAIDs reduce inflammation by acting on COX-2.
Common NSAIDs inhibit COX-1 and COX-2 to a similar extent; both produce prostaglandins. It was discovered in the 1990s that COX-2 is specifically activated during inflammatory responses, leading to the hypothesis that the therapeutic effect of NSAIDs is due to inhibition of pro-inflammatory COX-2, while the side effects are due to inhibition of constitutive, harmless COX-1. Therefore, pharmaceutical companies attempted to develop drugs that selectively inhibit COX-2, aiming for anti-inflammatory effects without side effects like impaired clotting or gastrointestinal symptoms.
In the end, the drugs developed had effects similar to common NSAIDs, with no reduction in side effects; they even promoted clotting by inhibiting COX-2 in vascular endothelial cells, reducing the production of the anti-clotting prostaglandin PGI2, increasing the risk of thrombosis. For example, Merck’s [[rofecoxib]] caused severe coronary heart disease in 140,000 people in the United States.
Currently, only [[celecoxib]] is in use, though its thrombosis risk is still under study.
Names
celecoxib
Brand name
- Celebrex
Personal evaluation
I haven’t reviewed the literature yet, so I don’t know how celecoxib differs from aspirin.