Non-opioid Analgesics

Two mechanisms under one heading. The NSAIDs — ibuprofen, naproxen, aspirin, diclofenac, ketorolac, celecoxib — inhibit cyclooxygenase and with it prostaglandin synthesis, which is where the analgesia comes from and equally where the gastrointestinal bleeding and the renal effects come from; celecoxib spares one isoform and shifts that balance rather than removing it. Paracetamol's mechanism is still not settled, and its risk is a different one entirely: hepatotoxicity through a metabolite the liver normally mops up.

The hidden hepatotoxicity is the combination pill. Paracetamol is the other half of most codeine, hydrocodone and oxycodone products, so escalating for opioid tolerance escalates something whose ceiling has nothing to do with tolerance — and liver injury is silent while it is happening, so feeling unremarkable is not evidence of not being in trouble. Metamizole is restricted or withdrawn in several countries over agranulocytosis.