NSAIDS have antipyretic activity and can be used to treat fever.   Fever is caused by elevated levels of prostaglandin E2 , which alters the firing rate of neurons within the hypothalamus that control thermoregulation.   Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis ( PGE2 ) within the hypothalamus .   PGE2 signals to the hypothalamus to increase the body's thermal set point.   Ibuprofen has been shown more effective as an antipyretic than paracetamol (acetaminophen).   Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.
Studies have shown that people who take anti-inflammatory painkillers have a small but significant increase in the risk of developing a heart attack or stroke . Although it can occur in anybody, the risk is mainly in people already known to have cardiovascular problems such as angina or peripheral arterial disease , and in the elderly. Perhaps the highest risk is in people who have previously had a heart attack. For example, one research study looked at people who had previously had a heart attack. The results showed a marked increase in the rate of a second heart attack in people who were taking an anti-inflammatory compared to those who were not.