Nonopioids

Nonopioids are analgesic and antipyretic medicines that do not act on opioid receptors. The category commonly includes acetaminophen (paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, and aspirin. Topical NSAIDs are also used in some pain conditions. In some classifications, selective COX-2 inhibitors (for example celecoxib) are considered part of the NSAID family.

Mechanisms of action vary. NSAIDs inhibit cyclooxygenase enzymes (COX-1 and/or COX-2), reducing prostaglandin synthesis and producing analgesic, antipyretic, and anti-inflammatory effects, with potential gastrointestinal and renal side effects. Acetaminophen has analgesic and antipyretic effects with little anti-inflammatory action; its precise mechanism is not fully agreed but is thought to involve central nervous system pathways. Overdose of acetaminophen can cause severe liver injury.

Indications include relief of mild to moderate pain and fever, such as headaches, dental pain, muscle aches, and inflammatory conditions. They are often used as alternatives to opioids or as adjuncts in multimodal analgesia. NSAIDs may be preferred when inflammation contributes to pain; acetaminophen is often chosen when NSAID use is limited by risk of stomach, kidney, or cardiovascular effects.

Safety considerations vary. NSAIDs can cause gastrointestinal irritation, ulcers, bleeding, kidney impairment, and cardiovascular issues, particularly with long-term use. Aspirin carries a bleeding risk and, in children, can be associated with Reye syndrome after viral infections. Celecoxib and other COX-2 inhibitors carry cardiovascular risks. Acetaminophen is generally safe at recommended doses but can cause severe liver injury in overdose or with chronic liver disease or heavy alcohol use. Consultation is advised for dosing in pregnancy, children, the elderly, and for individuals with comorbidities.