Pharm 101: Ibuprofen

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

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: XXX-XXX