Beyond analgesia: A comprehensive opinion review on the dual-action strategy of celecoxib and duloxetine in knee osteoarthritis

Figure 1 Sites of action (efficacy) of celecoxib and duloxetine. Celecoxib inhibits the cyclooxygenase-2 enzyme, reducing the production of prostaglandin E2 at the site of inflammation. Duloxetine increases serotonin and norepinephrine in the synaptic cleft, reinforcing the descending inhibitory pathway. COX-2: Cyclooxygenase-2.

Figure 2 Sites of side effects (toxicity) of celecoxib and duloxetine. Celecoxib selectively inhibits cyclooxygenase-2 with little effect on cyclooxygenase-1, thus reducing its inhibitory effect on platelet aggregation (prostacyclin) and relatively increasing its promoting effect (thromboxane A2), making thrombosis more likely and increasing the risk of myocardial infarction. Duloxetine can cause side effects in the brain (drowsiness) and the balance center (dizziness). Furthermore, their concomitant use increases the risk of effects on the gastric mucosa (synergistic effect on bleeding risk) and blood vessels (hyponatremia).