LEC 26 Inflammation and NSAIDs Flashcards
(41 cards)
What characterizes an inflammatory response?
- Transient local vasodilation
- Increased capillary permeability
- Infiltration of leukocytes and phagocytes
- Resolution with or without tissue degeneration and fibrosis
What are the prostanoids involved in an inflammatory response?
- Prostaglandin E2 (PGE2)
- Prostacyclin I2 (PGI2)
- Thromboxane A2 (TxA2)
Which two prostanoids are important for leukocyte attraction and adhesion to endothelial cells at a site of injury?
- PGE2
- TxA2
What effect to prostaglandins have on nocireceptors?
Prostaglandins increase the sensitivity of nocireceptors causing peripheral sensitization
Reveral of this is thought to be MOA of NSAIDs
Which prostanoid contributes to central sensitization?
PGE2
What part of the brain regulates body temperature?
Hypothalamus
How are fevers mediated?
- COX-2 generation of PGE2
- PGE2 crosses blood-brain barrier resulting in elevated body temp
NSAIDs inhibit COX-2 dependent PGE2 synthesis
How do NSAIDs work?
Inhibition of cyclooxygenase
Inhibition of COX-1 results in what?
- decreased platelet fxn
- removes gastric protection
Inhibition of COX-2 results in what?
- antipyretic
- analgesic and anti-inflammatory actions
Most NSAIDs are what kind of inhibitors of COX?
competitive, noncompetitive, or mixed REVERSIBLE
Aspirin is what kind of inhibitor of COX?
non-competitive, irreversible
Acetylates the isozyme in the AA-binding channel
What are the negative effects of COX-1 selective blockers?
GI toxicity
Ulcers, GI bleeds, stomach upset
What are the negative effects of COX-2 selective blockers?
Cardiovascular side effects
What is the common suffix for COX-2 selective inhibitors?
-coxib
What is the function of COX-1 normally?
- cytoprotective for gastric epithelial cells
- forms TXA2 in platelets and cause platelet activation and constriction of injured vessels
Largely accounts for gastric side effects via PGE2
What is the function of COX-2 normally?
- BP regulation and inhibitors of hemostasis
- Inhibition of COX-2 alone can cause HTN and an increase in thrombotic events
What is aspirin’s MOA?
- Acetylates serine 529 subunits of both COX 1 & 2 blocking AA
- inhibition occurs in the endothelial cells and platelets
- Endothelial cells can make new COX enzymes but platelets cannot (permenant inactivity for lifetime of platelet, 8-12 days)
How long after taking aspirin is enough for a partial platelet pool recovery for a simple surgery?
3 Days
Why is it important that synovial concentrations of NSAIDs are about half of the plasma concentration?
Makes NSAIDs effective for arthritis pain
Where are NSAIDs metabolized?
Liver then renal exretion
In the plasma, 95-99% of NSAIDs are found bound to what?
Plasma proteins like albumin
Why are NSAIDs not removed by hemodialysis?
d/t high protein binding in the plasma
What is the dose of a baby aspirin?
81 mg
