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
What is the MOA of Acetaminophen?
Unknown
What is the major toxicity associated with Acetaminophen?
Hepatotoxicity
What is the therapeutic dose of Acetaminophen?
15mg/kg
What dose of Acetaminophen produces liver necrosis?
150 mg/kg
What dose of Acetaminophen produces liver failure?
350 mg/kg
What is the MOA of Capsaicin?
- Binds vanilloid receptor
- Releases substance P
- Prolonged use depletes stores of Substance P in the PNS and spinal cord
This depletion of Substance P is analgesic
What do you need to remember about prescribing NSAIDs?
No one best NSAID for everyone
What is Gout associated with?
Hyperuricemia
What is the goal of gout therapy?
Control pain and inflammation
What is the primary drug to treat an acute gout attack?
Indomethacin
What is the MOA of Colchicine?
Anti-inflammatory effects mediated by inhibiting leukocyte migration and phagocytosis
What are the xanthine oxidase inhibitors?
Allopurinol
Febuxostat
How is allopurinol used clinically?
To prevent flares i.e. given between gout attacks
What is the MOA of Probenecid and Sulfinpyrazone?
Inhibit tubular absorption of uric acid and increase renal clearance of uric acid
When is Febuxostat prescribed typically?
When the patient stops tolerating Allopurinol
