The other major group of analgesics are nonsteroidal anti-inflammatory drugs (NSAID). They work by inhibiting the release of prostaglandins, which cause inflammatory pain. Acetaminophen/paracetamol is not always included in this class of medications. However, acetaminophen may be administered as a single medication or in combination with other analgesics (both NSAIDs and opioids). The alternatively prescribed NSAIDs such as ketoprofen and piroxicam have limited benefit in chronic pain disorders and with long-term use are associated with significant adverse effects. The use of selective NSAIDs designated as selective COX-2 inhibitors have significant cardiovascular and cerebrovascular risks which have limited their utilization.