In terms of inflammatory responses and underlying metabolic reactions, which of the following is inhibited by pharmacologic doses of glucocorticoids? (AIIMS May 2010)
|A||Cyclooxygenase (COX-1 and-2)|
|D||Phospholipase A2 (PLA2)|
a. Glucocorticoids ultimately inhibit phospholipase A activity. In doing so, they inhibit arachidonic acid synthesis and, therefore, synthesis of all products of the cyclooxygenase and lipoxygenase pathways, because both originate with arachidonic acid.
b. This action of glucocorticoids is indirect because their initial or direct effect is induced synthesis of annexins (previously called lipocortins); the annexins are the molecules that directly inhibit PLA activity Glucocorticoids have no intrinsic or direct inhibitory effects on later steps in AA metabolism, i.e., no effects on cyclooxygenase or lipoxygenase activity zileuton inhibits 5’-lipoxygenase.
c. We have no clinically useful inhibitors of histamine synthesis (which involves histidine decarboxylase activity).
d. Cyclooxygenases are inhibited by NSAIDs such as aspirin (nonselective COX-1 and -2 inhibitors) or the “coxibs” (celecoxib, rofecoxib, a few others) that relatively selectively inhibit COX-2.