Nonsteroidal Anti-Inflammatory Drugs

Incidence in USA: 100 million prescriptions are written per year; 17 million Americans use NSAIDs daily.

Have analgesic, anti-inflammatory, and antipyretic properties.

NSAIDs are the first step in the analgesic ladder of WHO; typically considered drugs of choice for mild to moderate pain.

Can be obtained OTC or by prescription for chronic somatic pain states (e.g., arthritis) and rheumatologic disorders.

Are given IV, IM, IN (intranasal ketorolac), and PO postop as part of a multimodal treatment regimen for acute pain.

Should be considered in an enhanced recovery protocol.

Plt dysfunction

Renal insufficiency

Drug interactions

Allergic reactions

Effect on bone growth

Gastric/GI bleeding

Possible increased risk of thrombotic/CV events with long-term use.

Most NSAIDs are weak acids (pK _a 3–5) of diverse chemical structure and half-lives.

Well absorbed from the stomach and intestinal mucosa.

Highly protein-bound (>95%), usually to albumin.

Work by inhibiting cyclooxygenase, which is a key enzyme in the synthesis pathway of prostaglandins.

• Lead to decreased prostaglandin synthesis, thus decreasing the inflammatory response as well as the sensitizing effect of prostaglandins on nociceptors (both central and peripheral).

Two isoforms of the COX enzyme have been identified.

• COX-1: Expressed constitutively in most cell types; has an essential role in functions such as gastric protection, plt aggregation, and renal function.

• COX-2: Traditionally considered to be induced by tissue injury/inflammation, now known to be constitutively expressed in some tissues (e.g., brain and/or kidney).

Undergo liver metabolism to inactive metabolites, which are then excreted by the kidney.

Have a low abuse potential but also a ceiling analgesic effect.