COX2preferential

COX2preferential refers to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit the cyclooxygenase-2 (COX-2) enzyme more potently than cyclooxygenase-1 (COX-1). This distinction matters because COX-2 is largely inducible at sites of inflammation, while COX-1 is constitutively expressed and contributes to gastric mucosal protection and platelet function. Drugs described as COX2preferential have higher affinity or efficacy at COX-2 relative to COX-1, but they are not necessarily exclusive COX-2 inhibitors.

Pharmacology and terminology: Inhibitory selectivity is often expressed by comparing IC50 or Ki values for COX-1 and COX-2. The degree of selectivity can vary with dose, tissue, and assay conditions. COX2preferential NSAIDs aim to reduce inflammatory prostaglandins while minimizing COX-1–mediated adverse effects, especially gastrointestinal toxicity, though complete safety is not guaranteed.

Examples and spectrum: Celecoxib is widely cited as COX-2 selective. Meloxicam is frequently described as COX-2 preferential at therapeutic doses, with some COX-2 selectivity evident at higher doses. Other agents, such as etodolac or certain arylacetic acids, may also be characterized as COX-2 preferential to varying extents. Highly COX-2–selective drugs (true COX-2 inhibitors) include drugs historically developed for that purpose, though several have faced safety and regulatory challenges.

Clinical considerations: COX2preferential NSAIDs can offer GI safety advantages relative to nonselective NSAIDs but may carry cardiovascular risks, particularly with higher doses or long-term use. The risk-benefit profile is individualized and guided by clinical guidelines and patient factors.

Regulatory context: Some COX-2–preferential or selective agents have undergone safety reviews or withdrawal due to cardiovascular or other concerns, leading to evolving recommendations and monitoring.

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