Snapshot A 40-year-old woman with a past medical history of alcoholism presents to her physician's office for pain with swallowing. She had been experiencing heartburn for the past few weeks. She also reports pain with swallowing for the past few days. She reports having occasional abdominal pain and severe migraines for which she had been taking multiple doses of aspirin and ibuprofen daily. She reports variable intake during the day but consistent intake of ibuprofen at bedtime. This is often done without water. She is counseled on the side effects of nonsteroidal anti-inflammatory drugs and given alternative medication for her migraines. (Pill-induced esophagitis) Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) categories of NSAIDs non-selective NSAIDs aspirin cyclooxygenase (COX)-2 inhibitors Mechanism inhibits COX-1, COX-2, or both ↓ formation of prostaglandins and thromboxanes Non-Selective NSAIDs Drugs diclofenac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen, piroxicam Mechanism reversible inhibition of COX-1 and COX-2 Clinical uses used as an analgesic, antipyretic, and anti-inflammatory medication used for niacin-induced red and flushed face indomethacin, specifically, is used to close the patent ductus arteriosus Toxicity interstitial nephritis renal ischemia ↓ prostaglandin (PG) E2 and PGI2 results in vasoconstriction of afferent arteriole renal papillary necrosis aplastic anemia gastric ulcers and bleeding ↓ PGE2 and PGE1 results in ↓ gastric mucosal protection pill-induced esophagitis Aspirin Drug aspirin (acetylsalicylic acid) is converted to salicylic acid in the body Mechanism irreversible inhibition of COX-1 and COX-2 by covalent acetylation Clinical uses anti-platelet aggregation at low doses (< 300 mg/day) antipyretic and analgesic at intermediate doses (300-2400 mg/day) anti-inflammatory medication at high doses (2400-4000 mg/day) Toxicity chronic toxicity interstitial nephritis acute renal failure gastric ulcers and bleeding pill-induced esophagitis decreases uric acid excretion avoid using aspirin in those with gout acute toxicity tinnitus and vertigo nausea and vomiting altered mental status noncardiac pulmonary edema mixed metabolic acidosis and respiratory alkalosis respiratory alkalosis early on from stimulation of respiratory centers in the medulla anion-gap metabolic acidosis from interference with oxidative phosphorylation and Krebs cycle, resulting in accumulation of lactic acid and ketoacids treatment sodium bicarbonate if used in children with viral infection, aspirin increases the risk for Reye syndrome Selective COX-2 Inhibitors Drug celecoxib Mechanism reversible inhibition of COX-2 specifically targets inflammatory cells and vascular endothelium spares COX-1 maintains the gastric mucosa and platelets less gastrointestinal bleeding Clinical use anti-inflammatory and analgesic medication typically used in rheumatoid arthritis and osteoarthritis Toxicity ↑ risk of thrombosis cross-hypersensitivity to sulfonamides