One enzyme, three benefits
Recall from guide 1 that COX makes prostaglandins, which sensitise nerves, drive inflammation and raise the brain's temperature set-point. An NSAID (non-steroidal anti-inflammatory drug — ibuprofen, naproxen, aspirin and many more) works by being a COX inhibitor: it blocks the enzyme so fewer prostaglandins form. The enzyme is the drug target. Knock it out and three benefits follow at once — less pain (analgesic), less swelling (anti-inflammatory), and a falling fever (antipyretic). One mechanism, the whole familiar trio.
The same target gives the harm
Here is the elegant, uncomfortable truth: not all prostaglandins are bad. Some protect the stomach lining (by holding back acid and keeping up protective mucus) and help keep blood flowing through the kidney. The COX enzyme comes in two main forms. COX-2 is switched on mostly at sites of inflammation — blocking it gives the relief. COX-1 runs all the time doing housekeeping, including that stomach protection. A typical NSAID blocks both, so the very same action that eases your pain also strips the stomach's defence, which is why long-term NSAID use can cause ulcers and bleeding. The benefit and the side effect flow from one target.
Drug designers tried to split the two: COX-2-selective NSAIDs spare the stomach better. But COX-2 also helps balance the cardiovascular system, so selective drugs carry their own heart risk — a clean illustration that you rarely get pure benefit from a single target. NSAIDs also reduce kidney blood flow and can blunt the action of some blood-pressure drugs, which matters most in the elderly and the dehydrated.
Paracetamol: the odd one out
Paracetamol (acetaminophen) relieves pain and fever like an NSAID, yet it is not counted as one — because it barely reduces inflammation in the body's tissues. Its exact mechanism is still debated, but it seems to act mainly in the brain rather than at sites of injury. The practical upshot: it is a good analgesic and antipyretic that is gentle on the stomach and safe in many people who cannot take NSAIDs. That is why it is a first-choice everyday painkiller worldwide.