NSAIDs and prostaglandin (PG) synthesis inhibition In 1971 Vane and coworkers made the landmark observation that aspirin and some NSAIDs blocked prostaglandin (PG) generation. This is now considered to be the major mechanism of action of NSAIDs. Prostaglandins, prostacyclin (PG I,) and thromboxane A, (TXA,) are produced from arachidonic acid by the enzyme cyclooxygenase (see p. 198) which exists in a constitutive (COX-1) and an inducible (COX-2) isoforms; the former serves physiological "house keeping functions, while the latter, normally present in minute quantities, is induced by cytokines and other signal molecules at the site of inflammation. This leads to generation of PGs locally which mediate many of the inflammatory changes. However, COX-2 is constitutively present at some sites in brain, in juxtaglomerular cells and in the foetus; it may serve physiological role at these sites. Most NSAIDs inhibit COX-1 and COX-2 nonselectively, bu...
