NSAIDs/APAP LOs

• What NSAID is commonly used in topical form

  Diclofenac
• Differences between classic NSAIDs and acetaminophen

  • NSAIDs have strong anti-inflammatory, analgesic and antipyretic effect
  • Acetaminophen has strong analgesic and antipyretic effects but WEAK anti-inflammatory, possible inhibition of COX-3
• Pharmacologic reasoning of Gastrointestinal effects

  1. Inhibition of COX-1 reduce beneficial levels of PGI2, PGE2, PGF2a
  2. PGI2- inhibits gastric acid secretion
  3. PGE2 and PGF2a- stimulate synthesis of protective mucus in both the stomach and small intestine
  4. Increased gastric acid secretion and decreased mucus production
  5. Increased risk of GI bleed and ulceration
  6. Dyspepsia
  7. Take with food to help reduce GI adverse effects
  8. NSAIDs can acause increased risk of serious GI effects especially in elderly including bleeding, ulceration, and perforation, which can be fatal
• Pharmacologic reasoning of increased bleeding risk

  1. Most NSAIDs reversibly inhibit production of TXA2
  2. Not clinically used for antiplatelet effects
  3. Can still prolong bleeding time
  4. More COX-2 selective agents have less effect on platelet inhibition and bleeding time
  5. Aspirin irreversibly inhibits COX-1 mediated TXA2 formation
  6. Platelets cannot synthesize new TXA2 when inhibited by aspirin, leading to decreased platelet aggregation/thrombus formation
  7. Effect lasts for life of platelet, ~3 to 7 days
• Pharmacologic reasoning of renal effects

  1. PGE2 and PGI2 are responsible for maintaining renal blood flow
  2. Decreased synthesis of prostaglandins leads to retention of sodium and water edema
  3. Can lessen effects of antihypertensive medications
• Pharmacologic reasoning of cardiac effects

  1. Agents (such as aspirin) w/ very high COX-1 selectivity have CV benefit
  2. Previous theory: Agents with high COX-2 selectivity are associated with increased risk for serious cardiovascular events including MI and stroke
  3. This risk has been associated with all NSAIDs other than aspirin
  4. Avoid chronic use
  5. Contraindicated for use in treatment of perioperative pain in coronary artery bypass graft (CABG) surgery
  6. NSAIDs may cause increased risk of serious CV thrombotic events, MI, and stroke. Risk may be increased in patients w/ CV disease or risk factors
• What one NSAID is known to provide cardiovascular benefit

  Aspirin