An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). The word analgesic derives from Greek an- ("without") and -algia ("pain"). Analgesic drugs act in various ways on the peripheral and central nervous systems; they include paracetamol (acetaminophen), the non-steroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others.

In choosing analgesia, the severity and response to other medication determines the choice of agent; the WHO pain ladder, originally developed in cancer-related pain, is widely applied to find suitable drugs in a stepwise manner. The choice of analgesia is also determined by the type of pain: for neuropathic pain, traditional analgesia is less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants.

Paracetamol and NSAIDs

main: Non-steroidal anti-inflammatory drug The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it appears to be acting centrally. Aspirin and the other NSAIDs inhibit cyclooxygenase, leading to a decrease in prostaglandin production; this reduces pain and also inflammation (in contrast to paracetamol and the opioids).Fact: date=February 2007 Paracetamol has few side effects and is regarded as very safe, although excessive doses lead to Analgesic Abuse Nephropathy (AAN) which is commonly caused by cumulative lifetime use of large amounts (≥ 2 kg) (ref. Merck Manual) and hepatotoxicity (liver damage). NSAIDs predispose to peptic ulcers, renal failure, allergic reactions, and occasionally hearing loss, and they can increase the risk of hemorrhage by affecting platelet function.Fact: date=February 2007 The use of aspirin in children under 16 suffering from viral illness may contribute to Reye's syndrome.

COX-2 inhibitors

main: COX-2 inhibitor These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested that most of the adverse effects of NSAIDs were mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as rofecoxib and celecoxib) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular. However, post-launch data indicated increased risk of cardiac and cerebrovascular events with these drugs due to an increased likelihood of clotting in the blood due to a decrease in the production of protoglandin around the platelets causing less clotting factor to be released, and rofecoxib was subsequently withdrawn from the market. The role for this class of drug is debated.