NSAIDs

Question 1

What is the MOA, actions, and uses of NSAIDs?

Answer 1

MOA: inhibition of cyclooxygenase which leads to inhibition of synthesis of prostaglandins and thromboxanes

Actions: anti-inflammatory, analgesic, antipyretic

Uses: mild-moderate pain especially pain of inflammation; musculoskeletal disorders, RA, OA, gout, ankylosing spondylitis, dysmenorrhea; aspirin 50% decrease risk of colon cancer; niacin induces flushing

Question 2

What are the nonselective COX inhibitors?

Answer 2

• Aspirin: irreversible
• Diclofenac
• Ibuprofen
• Indomethacin: DOC closure of ductus arteriosus
• Ketorolac
• Naproxen
• Piroxicam

Question 3

What are the COX-2 selective inhibitors?

Answer 3

• Celecoxib
• Meloxicam: not as selective for COX-2
• Rofecoxib and Valdecoxib: withdrawn bc of thrombotic events

Question 4

What are the AE of NSAIDs

Answer 4

• GI effects
• Cardiovascular effects
• Renal effects: decreased renal blood flow, analgesic nephropathy (phenacetin)
• NSAID-Exacerbated Respiratory Disease (NERD): vasomotor rhinitis, angioedema, urticaria, bronchial asthma, laryngeal edema, bronchoconstriction, flushing, hypotension, shock; from diversion of arachidonate to increase leukotrienes

Question 5

What can be done for GI AE caused by NSAIDs and what are the risk of each drug?

Answer 5

Misoprostol (PGE1 analog), PPIs, H2 blockers

• Lowest Risk: Celecoxib
• Low Risk: Ibuprofen, Aspirin, Diclofenac
• Medium Risk: Naproxen, Indomethacin
• High Risk: Piroxicam

Question 6

How do NSAIDs increase the risk of cardiovascular events?

Answer 6

• Upsetting the balance between TXA2 and PGI2 > vasoconstriction, platelet aggregation, thrombosis
• More COX-2 selective the more CV risk

Question 7

What are the CI, DI of NSAIDs and explain the triple whammy?

Answer 7

• CI: Reye’s syndrome in children and young adults less than 20 with fever associated with viral illness; pregnancy
• ACE-inhibitors, corticosteroids (increased risk of GI ulcers), warfarin (bleeding risk)
• The triple whammy is acute renal failure from combination of an ACE inhibitor or ARB, diuretic, and NSAID

Question 8

What is the actions of aspirins and other salicylates?

Answer 8

• Respiratory actions: elevated CO2 and increased respiration with higher doses stimulate hyperventilation and toxic levels causes central respiratory paralysis
• Increased risk of bleeding cause of irreversibly inhibits TXA2
• Anti-uricosuric effects because aspirin competes with uric acid for secretions
• Heptic injury in high doses
• Salicylism: mild chornic salicylate intoxication (salicylism) > HA, dizziness, tinnitus, mental confusion, hyperventilation

Question 9

What are the uses of aspirin?

Answer 9

• mild-moderate pain
• RA and other inflammatory joint conditions
• Potent antipyretic
• Low doses are cardioprotective

Question 10

Acetaminophen MOA, uses, AE

Answer 10

MOA: analgesic and antipyretic

Uses: mild-moderate pain; DOC OA, DOC children with fever and flu like syndrome, DOC short term tx of fever and inor pain during pregnancy

AE: hepatotoxin in overdose (acetylcysteine can be used)