Class

Non-selective reversible COX-inhibitor

Pharmacodynamics
  • Non-selective reversible COX-inhibitor
  • Suppresses inflammation primarily by inhibition of PG biosynthesis:
    • COX (cyclo-oxygenase) is key catalyst for conversion of arachidonic acid to PG
    • Reduces sensitivity of vessels to bradykinin and reverses vasodilation of inflammation
  • Other possible mechanisms:
    • Inhibition of chemostaxis
    • Down-regulation of IL-1 production
    • Decreased production of free radicals and superoxide
    • Interference with calcium-mediated intracellular events
  • Anti-inflammatory, antipyretic and analgesic actions
Pharmacokinetics
  • Weak organic acid
  • Well absorbed orally
  • Bioavailability 50-75% (no change with food)
  • > 99% protein binding
  • Half-life 2 hours
  • Extensive hepatic metabolism
  • Urinary excretion of unchanged drug < 1%
Clinical uses
  • Analgesic
  • Anti-inflammatory
  • Anti-pyretic
Adverse effects of NSAIDs
  • Bleeding secondary to inhibition of platelet aggregation
  • GIT:
    • Abdominal pain, nausea/vomiting
    • Ulcers
    • GI bleeding
  • Renal:
    • Nephrotoxicity
    • Hyperkalaemia
    • Proteinuria
  • CNS:
    • Headaches, tinnitus, dizziness
  • CVS:
    • Selective COX-2 inhibitors are implicated in increased risk of CVS thrombotic events
    • Fluid retention, edema
    • Hypertension
    • MI rarely
  • Haematological (rare):
    • Thrombocytopaenia, neutropenia, aplastic anaemia
  • Hepatic:
    • Deranged LFTs
  • Respiratory:
    • Asthma
  • Skin:
    • Rash
    • Pruritus

*Note ibuprofen has least GI upset out of NSAIDs

Precautions/contraindications
  • Pregnancy:
    • May cause closure of patent ductus arteriosus
  • Drug interactions (see below)
  • Others relate to above adverse effects
Drug interactions
  • Aspirin:
    • Ibuprofen antagonises platelet inhibition of aspirin and may increase risk of MI
    • Appears to block access of aspirin to active site on platelet
  • Lithium:
    • Increased serum levels
  • ACE-inhibitors:
    • Impairs hypotensive effects by blocking bradykinin-mediated vasodilation, which is at least partly PG-mediated
References
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

Follow him on twitter: @rob_buttner | ECG Library |

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