eliminate cause of injury & clear debris
What is the purpose of inflammation?
PGE2; Prostacyclin
What are the mediators of inflammation? (2)
increase: local BF, endothelial activation/vascular permeability, leukocyte infiltration
What are the effects of PGE2 & Prostacyclin? (3)
when source of pain is not cleared; inflammation will persist and cause pain
How does inflammation result in pain?
central PGE2 increases the excitability of spinal dorsal horn neurons-resulting in hyperalgesia/allodynia; COX1/COX2 are expressed in spinal cord and PG release upon peripheral pain stimuli
How is pain triggered in the CNS? (2)
nociceptors detect stimuli and send it to CNS; inflammatory mediators are released by damaged cells to increase sensitivity & potentiate pain/peripheral sensitization
How is pain triggered at the site of injury?
PGE2; thermosensitive
__________ can act on EP3 receptors on _________ neurons triggering the
hypothalamus to elevate body temperature.
arachidonic acid; cyclooxygenase (COX)
Prostaglandins are produced from _______ and this is catalyzed by _______.
b
Which is induced by inflammation?
a) COX-1
b) COX-2
a
Which is constantly expressed in noninflammatory cells?
a) COX-1
b) COX-2
a
Which is essential for TXA2 formation in platelets?
a) COX-1
b) COX-2
kidneys, gastric mucosa, platelet
Which organs/cells does COX-1 maintain homeostasis of? (3)
reduce PG synthesis by inhibiting COX enzymes
NSAIDs MOA?
anti-inflammatory, analgesic, antipyretic
What are the effects of NSAIDs? (3)
inhibit chemotaxis, decrease sensitivity of vessels to inflammatory mediators
What are the anti-inflammatory effects of NSAIDs? (2)
reverse peripheral sensitization & central actions in CNS
What are the analgesic effects of NSAIDs?
suppress the production of PGE2 to decrease hypothalamus signaling; reducing fever
What are the antipyretic effects of NSAIDs?
Age
__________ correlates with an increased probability of developing serious
AE to NSAIDs.
GI; CV
Nonselective COX inhibitors have an increased risk for _______ events
while Selective COX inhibitors have an increased risk for ________ events.
NSAIDs counter the effects of PG; resulting in retention of salt & water
How do NSAIDs cause Hypertension?
PG maintain patency of afferent arterioles; inhibition reduces BF to glomerulus which can result in AKI
How do NSAIDs decrease renal clearance?
pro-thrombotic events, hypertension, decreased renal clearance
What are the CV/Renal AE's of COX inhibition? (3)
decreases; PGI2
COX-2 inhibition _______ vascular ________.
PGI2
- a potent endogenous anti-platelet
premature closure of ductus arteriosus; HF in baby; avoid in 3rd trimester, prolonged gestation
What are the effects of NSAIDs in pregnancy? (2)
low
NSAIDs will accumulate in areas of the body with _____ pH.
they remain in the synovial fluid
What makes NSAIDs good for treating RA?
low-moderate pain, inflammation, fever, cardioprotection
What are the CAs of NSAIDs? (4)
oxaprozin, piroxicam, meloxicam
What are the longest-acting NSAIDs? (3)
piroxicam, meloxicam
Which NSAIDs are used for RA & OA? (2)