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 (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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