EXAM #4: NSAIDs AND GOUT Flashcards
What types of chronic conditions does inflammation underlie?
Asthma
RA
What are the four cardinal signs of inflammation?
1) Redness
2) Swelling
3) Heat
4) Pain
What are the non-AA and cytokine proinflammatory mediators?
Bradykinin
Substance P
Histamine
5-HT
What are the arachnadonic acid proinflammatory mediators?
Prostaglandins
Thromboxanes
Prostacyclin
What cytokine is highly proinflammatory?
TNF-a
What is the primary MOA / target of the NSAIDs?
Inhibition of prostglandin production by inhibiting COX-1 and COX-2
Is acetaminophen an NSAID?
NO
What is the general function of COX-1 and 2?
Conversion of arachnadonic acid to prostaglandins (PGE2 and PGI2)
What is the specific function of COX-1?
“Housekeeping”
- Maintains homeostasis
- Constitutively expressed
What is the important function associated with COX-1 and side effects of NSAIDs?
Synthesis of PG that protect the stomach lining
What is the specific function of COX-2?
- Production of inflammatory molecules
- PGI2
- “inducible”
Where in the AA pathway do corticosteroids block?
Phospholipase A2
What is the MOA of aspirin?
Hydrolyzed to salicylic acid, which is a reversible COX inhibitor
Why is there a high potential for drug-drugs interactions with aspirin?
Binds to plasma proteins
What are the dose-dependent effects of ASA at a LOW dose?
- Analgesia
- Antipyretic
What are the dose-dependent effects of ASA at a HIGH dose?
Anti-inflammatory
Describe the mechanism of the anti-pyretic effects seen with ASA?
- Blocks PG in the CNS to RESET temp. in thalamus
- Dilation of BV
- Sweating
- Decrease in temperature
How does ASA prolong bleeding time?
COX-1 inhibition prevents thromboxane formation
What are the major side effects associated with ASA?
1) GI Tract upset
2) GI irritation due to a loss of GI protective PGs
3) Platelet inhibition
List the non-selective COX inhibitors.
ASA Ibuprofen Indomethacin Ketorolac Naproxen Oxaprozin Piroxicam Sulindac
What is Indomethacin commonly used to treat?
1) Gout
2) Ankylosing spondylitis
What is the major advantage of COX-2 selective inhibitors?
Less side effects
What is the feared complication of COX-2 inhibitors?
Cardiovascular thrombotic events
List the COX-2 selective inhibitors.
Celecoxib
Etoricoxib
Meloxicam
