Inflammation and anti-inflammatories Flashcards
The local accumulation of fluid containing plasma proteins and white blood cells (WBCs)
Often non-specific (innate response)
Very dynamic (changing and different)
Local physiological response to injury
Responds to infection and cell death
An immediate response aims to…
Restrict damage or infection to a localised area.
Remove the causative agent and damaged tissue.
Promote immune cells (and molecules) access to the site to innate repair of damage tissue.
Innate: Non-specific defence mechanism - First line of defence
Skin
Mucous membrane
Secretions of the skin and mucous membranes
Innate: Non-specific mechanism - Second line of defence
Phagocytic white blood cells.
Antimicrobial proteins.
The inflammatory response.
Adaptive: Specific defence mechanism - Third line if defence
Lymphocytes
Antibodies
Cardinal signs of acute inflammation
Heat (Calor) Erythema (Rubor) Oedema (Tumour) Pain (Dalor) Loss of function
Innate responses that induce actute inflammation
- Bacteria trigger macrophages to release cytokines and chemokines.
- Vasodilation and increased vascular permeability cause redness, heat and swelling.
- Inflammatory calls migrate into tissue, releasing inflammatory mediators that cause pain.
Key cells recruited during acute inflammation
Macrophage
Dendritic cells
Mast cells
Mostly neutrophils
4 stages of inflammation
- Tissue damage
- Vasodilation
- Cell recruitment (phagocyte migration and margination)
- Tissue repair - Clotting, annexin (lipocortin) and fibrin release. Fibrin lays down collagen (scars)
Overview of inflammation
- Damage leads to activation of sentinel cells (via complement or phagocytosis), releasing cytokines (TNF-α, IL-1β), chemokines (IL-8), histamine and prostaglandins.
- Vasodilation and vascular permeability (histamine). Exudate of complement and cells.
- Extravasation and chemotaxis (IL-8), further cell recruitment = swelling
Eicosanoids
Group of physiologically active lipid compounds.
Signalling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid.
20 carbons in length
Prostanoids (prostaglandins and thromboxane)
Leukotrienes
Prostanoids formation
Membrane phospholipids + Phospholipase A2 ->
Arachidonic acid + Cyclo-oxygenase (COX) ->
Intermediate prostaglandin (PGH2) ->
Prostacyclin (PGI2) / Thromboxane (TXA2) / Prostaglandins(PGE2)
Prostacyclin (PGI2) induces…
- Vasodilation
2. Stops platelet activation
Thromboxane (TXA2) induces…
- Vasoconstriction
2. Activates platelets
Prostaglandins (PGE2) induces…
- Fever
- Pain
- Vascular permeability
Leukotrienes formation
Membrane phospholipids + Phospholipase A2 ->
Arachidonic acid + Lipooxygenase (LOX) ->
5-HPETE ->
Leukotrienes
Leukotrienes induce…
- Inflammation
2. Chemotactic effect on neutrophils
Dyspepsia meaning
Indigestion
Eicosanoids formation
1
Membrane phospholipids + Phospholipase A2 ->
Arachidonic acid + cyclo-oxygenase (COX) ->
Intermediate prostaglandin (PGH2) ->
PGI2/PGE2/TXA2
#2
Membrane phospholids + Phospholipae A2 ->
Arachidonic acid + Lipooxygenase (LOX) ->
5-HPETE ->
Leukotrienes
Drugs used to combat pain and inflammation
Antihistamines - Antagonists of the histamine receptors
NSAIDs - Non-steroidal anti-inflammatory drugs
Glucocorticoids - Steroidal anti-inflammatory drugs
Immuno-suppressants - Reduction of immune cell activation or response
NSAIDs and non-opioid analgesics: Paracetamol
Analgesic and antipyretic activity.
No anti-inflammatory action
Liver damage on overdose
NSAIDs and non-opioid analgesics: Ibroprofen
Short term analgesic and anti-inflammatory action.
Gastric irritation, increased rick of ulceration
FDA Cat. D drug
NSAIDs and non-opioid analgesics: Aspirin
Acetylates COX Irreversible inhibitor Anti-platelet activity Increased risk of gastrointestinal bleeding and irritation Bad for asthma patients
NSAIDs and non-opioid analgesics: Celecoxib
Specific COX-2 inhibitor
Fewer side effects
Suggested increased risk of stroke and heart attack following use FDA Cat. D drug
