Inflammation and Blood Clotting Flashcards
What is the most common cause of death?
Heart disease (29%)
What is the second largest cause of death?
Infectious diseases
What are the two biggest infectious diseases that kill people?
Malaria (3m deaths per year), tuberculosis (2m deaths per year)
Describe an inflammatory response
Body responds to infection, tissue damage or foreign bodies.
Increased blood flow to bring leukocytes to tissue
Increased permeability of endothelial cells lining blood vessels, so blood leaks into surrounding tissue
What are prostaglandins?
local inflammatory mediator released by endothelial cells in response to damage. Autocrine or paracrine. Produced by COX enzyme
Inhibits platelet aggregation
Stimulates leukocyte migration
Describe the pathway that produces prostaglandins
Archionic acid ->(Catalysed by COX) Prostaglandin H2 -> Prostaglanin variants or Thromboxane A2
What are thromboxanes?
Vasoconstrictors produced by endothelial cells that inhibit platelet aggregation. Reduces inflammation
How does a blood clot form
Prostacyclins promote blood clotting
Prothrombin activated to thrombin which converts fibrinogen to fibrin.
How do NSAIDs function?
Inhibit COX enzymes to prevent prostacyclin forming. This prevents vasodilation and inflammation.
Antipyretic (reduce fever)
Analgesic (reduce headache)
Why are NSAIDs used as opposed to steroids?
Less side effects
How does aspirin work?
Inhibits COX by irreversibly acetylating it.
Reduces thromboxane synthesis as well as prostaglandin. Low doses therefore reduce risk of heart attack
Prostaglandins protect stomach lining, so aspirin can cause gastic bleeding and stomach ulcers
How are NSAIDs design to reduce gastric irritation?
Inhibit COX-2 isoform as this is found more in inflamed tissue
e.g Vioxx
Why were Viox COXIBs taken off the market in 2004?
Meta analysis found 2.24x greater risk of heart attack
