NSAIDs

Structure/Class  
Pharmacodynamics
  1. NSAIDs function by inhibiting COX and therefore leading to less prostaglandin synthesis.
    • Aspirin irreversibly inhibits COX.
    • Non-COX selective NSAIDs reversibly inhibit COX.
    • Selective COX-2 NSAIDs will not have anti-platelet function.
  2. Comparative effects as follows:
    • COX-2 drugs have less GI effects, but increased oedema and HTN.
    • NSAIDs overall will decrease the sensitivity of blood vessels to bradykinin and histamine, affect lymphokine production from T-cells and reverse vasodilation associated with inflammation.
      1. All NSAIDs will have analgesic/anti-pyretic and anti-inflammatory effects.
    • All NSAIDs (except the COX-2 specific ones) have anti-platelet activity.
    • Some NSAIDs (including aspirin) are thought to reduce colon cancer risk.
    • With respect to GI effects:
      1. Ibuprofen thought to have the least GIT effects.
      2. Piroxicam has 9x the GIT effects.
      3. Aspirin has double the GIT effects.
      4. Indomethacin may cause pancreatitis.
Absorption/administration
  1. PO. Some may be given IV or IM.
    • Importantly, food does not lower its bioavailability.
Distribution
  1. All are weak acids and therefore absorbed well in the GIT.
  2. They are all highly protein bound (>98% to albumin).
  3. They are all found in high concentration in synovial fluids.
Metabolism
  1. Hepatic, by CYP systems and phase 2 reactions.
Excretion
  1. Renal
Indications  
Contraindications  
Special precautions  
Interactions
  1. Lithium – may increase lithium levels secondary to reducing renal blood flow.
  2. Increased risk of bleeding with other anticoagulants.
Adverse events
  1. Toxic effects
    • Mainly GIT (gastritis, nausea/vomiting, ulcers and bleeding)
    • Renal – AKI (probably secondary to altered renal blood flow due to reduced prostaglandin synthesis)
    • Hepatic – abnormal LFTs and rarely, hepatic failure.
    • CNS – tinnitus, dizziness and headaches.
Dosing/administration  
Toxicology
  1. Good supportive care

 
Withdrawal syndrome  
Special notes