Aspirin's actions begin with its effects on two important enzymes, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Think of COX-1 as a "housekeeping" enzyme because it's present in many tissues, where it helps maintain various functions. For the most part, COX-1 does its job by stimulating a family of chemicals called prostaglandins.
A particular prostaglandin (thromboxane A2) is the "glue" that makes platelets stick together and form clots. By inhibiting COX-1, aspirin interrupts this chain of events and reduces the risk of heart attacks. But since platelets also trigger the "good" clots that stanch bleeding from injured tissues, aspirin increases bleeding, whether from a shaving nick or a serious wound.
Prostaglandins in the stomach stimulate gastric blood flow and the production of acid-neutralizing bicarbonate and protective mucus. By inhibiting COX-1, aspirin reduces prostaglandins that protect the stomach, increasing the risk of bleeding and ulcers.
Prostaglandins also help regulate kidney function and blood flow. By inhibiting COX-1, aspirin can reduce these protective chemicals, sometimes raising blood pressure or reducing kidney function, especially in the elderly or in patients with kidney disease.
If COX-1 is a housekeeping enzyme, COX-2 is more of a troubleshooter. Instead of hanging around in healthy cells and tissues, it gets fired up in response to assaults such as infection and inflammation. COX-2 generates chemicals that trigger fever and pain; drugs that inhibit COX-2 do a nice job of reducing pain and lowering high temperatures. But COX-2 is not all bad; it also produces prostacyclin, a chemical that widens arteries and fights blood clotting. Drugs that inhibit COX-2 may increase the risk of heart attack and stroke by reducing prostacyclin. That's why the selective COX-2 inhibitors rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market, while a third one, celecoxib (Celebrex) requires extreme care. And it's also why the many nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit both COX-1 and COX-2 have a mixed reputation (more on that later).