more COX protein, are irreversibly affected by aspirin but only temporarily
affected by other NSAIDs. Low-dose aspirin is often used in antithrombotic
The prothrombotic and vasoconstrictive actions of COX-1-derived throm-
boxane in the vasculature are opposed by an antithrombotic and vasodilative
prostaglandin, prostacyclin, that originates from COX-2 in vascular endothe-
lial cells. The COX-2 selective coxibs thus tend to decrease prostacyclin lev-
els in the vasculature without reducing the thromboxane levels. This tendency
is thought to explain the small but significant increase in cardiovascular risk
that recently led to withdrawal of two coxibs from the U.S. market.
A PPR O A C H TO PR O ST A G L A N D IN M E T A B O L ISM
Describe the biosynthetic and cell signaling pathways involving
Distinguish between the pathophysiologic roles of the two PGHS
Cite the pharmacologic targets of NSAIDs and the characteristics that
distinguish coxibs and aspirin from other NSAIDs.
Eicosanoids: Oxygenated lipid signaling molecules containing 20 carbons
derived from polyunsaturated fatty acids released from membrane phos-
pholipids by the action of phospholipase A2. These include the prostanoids
produced by the cyclooxygenase pathway and the leukotrienes produced
by the lipoxygenase pathway.
Prostanoids: Oxygenated lipid signaling molecules derived from polyun-
saturated fatty acids released from membrane phospholipids by the
action of phospholipase A2. Prostanoids include prostaglandins, prosta-
cyclin, and thromboxanes.
Prostaglandin: An oxygenated lipid signaling molecule that has a five-
member ring system that is derived from arachidonic acid and other 20-
carbon polyunsaturated fatty acids. The prostaglandins are hormone-like
molecules that regulate cellular events near the area in which they are
Thromboxane: An oxygenated lipid signaling molecule that has a six-
member ring system derived from arachidonic acid and other 20-carbon
polyunsaturated fatty acids. Thromboxanes are involved in platelet
aggregation as well as vaso- and bronchoconstriction and lymphocyte