Pharmacology of Inflammation Flashcards
What are the five cardinal signs of inflammation?
Heat Redness Swelling Pain Loss of Function
What are SAIDs and its examples?
Steroidal Anti-Inflammatory Drugs: Glucocorticoids (hydrocortisone, prednisolone, dexamethasone)
What are NSAIDs and its examples?
Non-steroidal anti-inflammatory drugs: ibuprofen (nurofen and advil), diclofenac (voltaren) and naproxen (Naprogesic and Feminax)
What are inflammatory mediators?
intercellular chemical messengers released by inflammatory cells
What are the major inflammatory mediators?
Eicosanoids Histamine Platelet Activating Factor (PAF) C5a all not stored they are synthesized and released in response to inflammatory stimuli except for histamine
Which major inflammatory mediator is the target of anti-inflammatory drugs?
Eicosanoids: oxygenated derivatives of arachidonic acid including protoglandins and leukotrienes
What is the mechanism of the creation of Eicosanoids
Arachidonic acid is originally esterified to membrane phospholipids then Phospholipase A2 turns it into free cytosolic arachidonic acid then two pathways occur
- ) 5-Lipoxygenase turns it into leukotriense, LTB4, LTC4, LTD4
- ) COX-1 and COX-2 occur together and turn it into Prostoglandins and thromboxane
What is the SAIDs mechanism of action?
Can freely cross the lipid bilayer using the nuclear receptor method it creates Annexin-1 which blocks Phospholipase A2 so it stops the release of arachidonic acid and all other steps
What are some long-term effects of glucocorticoid use?
cataract mental disturbances osteoperosis Cushing's Syndrome Suppression of HPA axis dyspepsia avascular necrosis
What is the best way to take someone off of glucocorticoids?
Slowly ween them off it so the body can be allowed to return to it’s normal equilibrium
How do SAIDs affect the inflammation process?
reduction of innate and acquired immune system with reduction in protective aspects and potential reduction in healing
What is the NSAIDs mechanism of action?
Inhibits COX enzymes and inhibits the syntheses of prostaglandins and thromboxanes thereby reducing inflammation
What is the difference between what COX-1 and COX-2 produce
COX-1: has physiologic function, homeostatic housekeeping cytokines which assit with regulation of kidney blood flow, gastric cytoprotection, inhibition can lead to harmful effects like mucosal damage
COX-2: has inflammation effects, produces inflammatory Prostoglandins and inhibition has anti-inflammatory effects
What are the NSAIDs three multiple actions
1.) anti-inflammatory: by reducing COX-2 activity they can reduce inflammation to varying degrees by directly reducing synthesis of PGs involved in vasodialtion and indirectly by reducing the access of histamine which would increase permeability of post-capillary venules
2.) Anti-pyretic: fevers happen when hypothalamic IL-1 generates PG-E that elevates the temperature set point, NSAIDs interrupt the synthesis of PG-E and the resetting of the setpoint and the body adjust to restore normal body temperature
3.) Analgesic: indirectly by decreasing the production of PGs which would normally sensitise the nerve endings to pain producing mediators
good for arthritis, bursitis, dysmenorrhea, postpartum pain etc.
What does aspirin do?
Blocks COX-1 and COX-2 at a >10:1 ratio so can damage the stomach and a higher dosage is usually taken for anti-inflammatory effects
also inhibits thromboxane formation so is a good anticoagulant
