Nonsteroidal Antiinflammatory Drugs (NSAIDs) • • • • • Common therapeutic indications Common adverse effects Different pharmacokinetics and potency Different chemical families Common mechanism of action (cyclooxygenase inhibition) • Different selectivities to COX I and II Similarities more striking than Differences Common Pharmacological Effects • Analgesic (CNS and peripheral effect) may involve non-PG related effects • Antipyretic (CNS effect) • Anti-inflammatory (except acetaminophen) due mainly to PG inhibition. Some shown to inhibit activation, aggregation, adhesion of neutrophils & release of lysosomal enzymes • Some are Uricosuric Common Adverse Effects • Platelet Dysfunction • Gastritis and peptic ulceration with bleeding (inhibition of PG + other effects) • Acute Renal Failure in susceptible • Sodium+ water retention and edema • Analgesic nephropathy • Prolongation of gestation and inhibition of labor. • Hypersenstivity (not immunologic but due to PG inhibition) NSAID Loss of PGI2 induced inhibition of LTB4 mediated endothelial adhesion and activation of neutrophils ↑ Leukocyte-Endothelial Interactions Capillary Obstruction Proteases + Oxygen Radicals Ischemic Cell Injury Endo/Epithelial Cell Injury Mucosal Ulceration The Salicylates – Aspirin • Effect on Respiration: triphasic 1. Low doses: uncoupling phosphorylation → ↑ CO2 → stimulates respiration.
