CLASIFICATION OF THE MAJOR EICOSANOIDS OF PHARMACOLOGICAL INTEREST

COX-2 Inhibitors: inhibit cyclooxygenase of the number 2 isoform, thereby inhibiting prostaglandins and thromboxanes from forming so pain and fever and inflammation are not produced. (This is contrasted with non-specific COX inhibitors such as Advil and Aspirin, which inhibit other cyclooxygenases as well).

Although the textbook shows it as cyclooxygenase, there are really 2 isoforms! The prostaglandins that cause problems are PGE1 and PGE2. Prostacyclins (PGI2) are mostly involved with vascular control (vasodilator and anti-platelet substance) and not really involved with pain. Thromboxane is inhibited by aspirin, which has an anti-platelet effect. So when we’re talking about pain, we’re talking about blocking PGE1 and PGE2 by inhibiting the cyclooxygenase; drugs like aspirin and advil are not blocking the prostaglandin receptor, but instead are blocking the production of the mediator by inhibiting the rate-limiting-enzyme.


In 1985 it was found that there are more than one cyclooxygenase. COX-1 is always present in all tissues, it is “constitutive” (always there). The COX-2 enzyme is inducible, once COX-2 is induced it produces prostaglandins pain and inflammation. So to treat pain, it is best to inhibit COX-2. Many OTC drugs (aspirin, advil, etc) are not specific and so there are other effects on the platelet, etc. besides just analgesia effects.

COX-2 specific inhibitors currently available are celecoxib (Celebrex) and rofecoxib (Vioxx). These are heavily advertised drugs. Whenever you see a suffix –coxib, think of a COX-2 specific inhibitor.

Category: Pharmacology Notes