Lecture Notes: Inflammation and Anti-Inflammatory Medications

Learning Objectives

• Chemical Mediators of Inflammation
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Steroidal Anti-Inflammatory Medications

Inflammatory Process Recap

• Trigger: Damage/injury to vascularized tissue
• Vascular Response: Initial stage of inflammation
• Cardinal Signs:
  • Redness
  • Heat
  • Swelling
  • Pain

Mechanism of Inflammation

• Vasodilation: Blood vessels dilate, increasing blood flow to the injured site.
• Endothelial Constriction: Endothelial cells contract, increasing permeability and allowing fluids to escape into surrounding tissues.
• Role of Chemical Mediators:
  • Prostaglandins
  • Leukotrienes
  • Nitric Oxide
  • Bradykinins
  • Histamine
  • Cytokines

Chemical Mediators: Prostaglandins and Leukotrienes

• Phospholipid Bilayer: Cell membrane components leading to production of arachidonic acid.
• Arachidonic Acid Pathway:
  • Produces prostaglandins and leukotrienes.
• Prostaglandins:
  • Functions:
    • Inflammation
    • Pain
    • Fever
  • Additional Roles:
    • Maintaining GI integrity
    • Promoting platelet aggregation
  • Differentiation: Cox-1 and Cox-2 pathways
• Leukotrienes:
  • Inflammation
  • Mucus secretion (especially in airways)
  • Bronchoconstriction
  • Significant role in asthma

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Types:
  • Aspirin
  • Ibuprofen
  • Paracetamol
  • Celecoxib
• Common Mechanism: Inhibit Cox enzymes (Cyclooxygenase)
  • Cox-1: GI protection, platelet aggregation, inflammation, pain, fever
  • Cox-2: Inflammation, pain, fever, role in rheumatoid arthritis, reduced platelet aggregation
• Specific NSAIDs:
  • Aspirin:
    • Inhibits Cox-1 & Cox-2
    • Reduces inflammation, pain, fever
    • GI side effects due to reduced mucous lining
    • Used for cardiovascular disease prevention
  • Ibuprofen:
    • Inhibits Cox-1 & Cox-2
    • Similar effects to aspirin
  • Paracetamol:
    • Effective analgesic & antipyretic
    • Poor anti-inflammatory
    • Might inhibit a third Cox isoform (Cox-3)
  • Celecoxib:
    • Cox-2 specific inhibitor
    • Used in rheumatoid arthritis
    • Reduces risks of GI side effects associated with Cox-1 inhibition
    • Potential clotting risks
• Role in Asthma: Relevant due to leukotrienes-mediated inflammation.

Steroidal Anti-Inflammatory Drugs

• Glucocorticoids (Corticosteroids): Derived from adrenal cortex (e.g., hydrocortisone/cortisone)
  • Mechanism:
    • Inhibit phospholipid to arachidonic acid conversion
    • Alter gene transcription (reduce pro-inflammatory gene expression)
  • Effects:
    • Potent anti-inflammatory
    • Systemic effects noted (e.g., glucose regulation)`