NSAIDs/APAP Meds

• NSAIDs include the following

  • Aspirin
  • Ibuprofen (Advil, Motrin)
  • Naproxen (Aleve)
  • Indomethacin
  • Sulindac
  • Ketorolac
  • Meloxicam
  • Diclofenac
  • Celecoxib (Celebrex)
• NSAIDs

  • Nonselective inhibitors of both COX-1 and COX-2
  • GI effects, increased risk of bleeding, edema, can slightly increase leukotriene production (exacerbation of asthma), CNS effects (headache, tinnitus, dizziness), renal and hepatic toxicity, acute renal failure, hypersensitivity
  • Category C in 1st/2nd trimester, avoid use in 3rd trimester (risk of premature closure of ductus arteriosus)
• Celecoxib MOA

  Selective COX-2 inhibitor, does NOT inhibit platelet aggregation

  • This is the only remaining COX-2 inhibitor on market
• Aspirin

  • Clinical effect dependent on dosage
  • Risk of Reye’s syndrome - do not use in individuals under the age of 20
  • May decrease uric acid excretion so be cautious in gout
• Ibuprofen and Naproxen

  • Among most widely used NSAIDs
  • Low doses available OTC, High doses require rx
  • Oral, ibuprofen also available as injectable
  • Half-lives: naproxen is about 14 hours (twice daily dosing), ibuprofen is about 2 hours (2-4 times daily dosing)
• Indomethacin

  • One of most potent inhibitors of COX isozymes
  • Higher incidence of adverse effects, reserve for moderate to severe acute inflammation not controlled by other NSAIDs
  • Also used to accelerate closure of patent ductus arteriosus in premature infants
• Sulindac

  Noted for having a “renal-sparing” effect; moderate doses alter renal prostaglandin production less than other NSAIDs
• Ketorolac

  • Exhibits potent analgesic activity- analgesia comparable to morphine but less nausea, vomiting, and drowsiness
  • Available in oral, parenteral, or intranasal form
  • Use limited to 5 or fewer days due to significant risk of hematologic toxicity and other adverse effects
• Meloxicam

  More selective for COX-2 then typical NSAIDs but not as selective as celecoxib
• Diclofenac available as oral, transdermal patch, or topical
• Acetaminophen

  • Uncertain MOA, centrally acting, possible inhibition of COX-3
  • Well tolerated, hepatic necrosis (dose related, can be lethal)
  • Small amount of acetaminophen converted to potentially hepatotoxic N-acetyl-p-benzoquinoneimine (NAPQI), at therapeutic doses NAPQI is inactivated but at toxic doses accumulation leads to hepatic necrosis, N-acetylcysteine used to treat patient w/ toxic doses
  • Oral or IV
  • Substitute for NSAIDs when analgesic and/or antipyretic effects needed, DOC for pregnancy, good alternative for children with viral infections who cannot take aspirin