Inflammation and Anti-inflammatories

• What is the first step in acute inflammation?

  Tissue damage
• What mediators are released during acute inflammation?

  Histamine, prostaglandins, bradykinin/nitric oxide
• What is the role of immune cells in inflammation?

  They are recruited to the site of damage
• What are the five cardinal signs of inflammation?

  Heat, redness, swelling, pain, loss of function
• How can the cardinal signs of inflammation be explained?

  • Vasodilation increases blood flow
  • Extravasation of leukocytes occurs
  • Proteins leak into extracellular fluid
  • Osmosis causes water movement into ECF
  • Prostaglandins and histamine activate pain neurons
• What is the effect of vasodilation during inflammation?

  Increases blood flow to the area
• What happens during extravasation of leukocytes?

  Leukocytes move into surrounding tissue
• What causes pain during inflammation?

  Activation of neurons by prostaglandins and histamine
• What is the primary aim of acute inflammation?

  To recruit cells to aid healing
• What can frequent release of inflammatory mediators lead to?

  Chronic inflammation and fibrosis
• What is the first step in the arachidonic acid pathway?

  Inflammation
• What is arachidonic acid derived from?

  Phospholipids in cell membranes
• What are some types of prostaglandins produced?

  PGD2, PGE2, PGI2, PGF2, TXA2
• What effects do prostaglandins have?

  Vasodilation, pain, fever
• What is the role of PGD2 and PGI2?

  Vasodilation and inhibit platelet aggregation
• What does TXA2 do?

  Causes vasoconstriction and platelet aggregation
• What is the main inflammatory prostanoid?

  PGE2
• What are the functions of prostaglandin receptors?

  • EP1: Contraction of bronchial and GI smooth muscle
  • EP2: Bronchodilation and vasodilation
  • EP3: Contraction of intestinal smooth muscle
  • EP4: Similar to EP2, inhibits PGE2 on leukocytes
• What type of receptors are prostaglandin receptors?

  G-protein coupled receptors (GPCRs)
• How does PGE2 differ from other prostaglandins?

  It has the greatest number of receptors
• What does the PGI2 receptor couple with?

  Gs protein
• What is the significance of multiple prostaglandin receptors?

  • One receptor means same action in all tissues
  • Multiple receptors mean different actions in different tissues
• What do leukotrienes cause?

  Bronchoconstriction and increased vascular permeability
• What type of receptors do leukotrienes use?

  G-protein coupled receptors (GPCRs)
• What is the response of leukotriene receptors?

  They mediate a broad inflammatory response
• What does cyclooxygenase produce?

  PGG2 and PGH2
• What is COX-1 characterized by?

  Constitutive and widespread
• What is the role of PGE2 produced by COX-1?

  It is protective in the stomach
• What does the COX-1 subtype in platelets produce?

  TXA2 for aggregation
• How is COX-1 inhibited?

  By small molecules through a small hydrophobic channel
• What is COX-2 characterized by?

  Inducible and increased by cytokines
• Where is COX-2 found besides inflamed areas?

  In endothelial cells and the CNS
• What does COX-2 produce to prevent aggregation?
• How does COX-2 differ from COX-1 in terms of inhibition?

  COX-2 has a larger channel for bulky drugs
• What does NSAID stand for?

  Non-steroidal anti-inflammatory drugs
• What is the action of aspirin as an NSAID?

  Irreversible covalent modification
• How does ibuprofen act as an NSAID?

  It acts through reversible inhibition
• Which NSAIDs are COX-1 selective?

  Keterolac and Flurbiprofen
• Which NSAIDs are COX-2 selective?

  Celecoxib and Rofecoxib
• What are common side effects of NSAIDs?

  GI bleeding and cardiovascular risk