Valdecoxib is an oral non-steroidal anti-inflammatory drug given to treat osteoarthritis and dysmenorrhoea. It targets the prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Valdecoxib enters the cell via the solute carrier family 22-member 8 transporter and inhibits the action of COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2. The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Side effects of valdecoxib may include diarrhea, nausea, upset stomach, headache, indigestion, stomach cramps, upper respiratory tract infection (nose, throat, or sinuses), back pain, dizziness, gas, muscle pain, rash, and stuffy nose.

Valdecoxib Pathway (New) References