Osteoarthritis and Joint Inflammation

Question 1

drugs for osteoarthritis

Answer 1

Analgesics:
-acetaminophen
-Tramadol, codeine (narcotic)
Anti-infl agents:
-NSAIDs
-NSAIDs + gastric anti-secretory agent
-triamcinolone (corticosteroid)

Question 2

1st step for pain relief in osteoarthritis

Answer 2

Acetaminophen

-only an analgesic; not an anti-infl agent!!!

Question 3

Acetaminophen metabolism

Answer 3

• CYP450–> NAPQI

- NAPQI metabolized by GSH

Question 4

acetaminophen overdose

Answer 4

• overproduction of NAPQI
• depletion of cells’ glutathione content
• failure to detoxify NAPQI via GSH adduct
• NAPQI reacts irreversibly with cell proteins
• catastrophic cell damage!!

Question 5

CYP450 generates?

Answer 5

hepatotoxic NAPQI

• NAPQI modifies cell proteins
• centrolobular necrosis

Question 6

Acetaminophen/NAPQI Hepatotoxicity- course

Answer 6

• 0-24 hrs- N/V, abd pain
• 24-72 hrs- RUQ pain, evolving liver damage
• 72-96 hrs- LETHAL- inc AST/ALT, coagulopathy, kidney failure, coma, death

Question 7

Acetaminophen overdose- antidote

Answer 7

NAC (N-Acetylcysteine)

• give early as possible during 1st 24 hrs
• replenishes GSH pool
• GSH substitute- reacts directly with NAPQI- spares proteins and salvages cells

Question 8

NSAIDs- agents for osteoarthritis

Answer 8

(analgesic and anti-infl)

-OA progression–> inflammation

Question 9

NSAIDs- over-the counter in US

Answer 9

• ibuprofen

- naproxen

Question 10

if mild, sx OA- prescribe what?

Answer 10

Acetaminophen!!

-if sx’s persist or when dz progresses (more pain, infl)- prescribe NSAID!!!

Question 11

acetaminophen vs tNSAIDs

Answer 11

• acetaminophen = ibuprofen for mild/moderate pain

- in most trials, pts prever ibuprofen over acetaminophen for OA w severe pain

Question 12

Only US NSAID in injectable formulation

Answer 12

Ketorolac

Question 13

Choosing NSAIDs

Answer 13

• efficacy (all are equally efficacious)
• safety- HTN, atherosclerosis, smoking!!!
• pharmocokinetics

Question 14

only a single NSAID should be used at any given time

Answer 14

• exception- use of cardioprotective aspirin with other NSAIDs
• risk for GI bleeding

Question 15

NSAIDs and aspirin

Answer 15

• alleviate infl- inhibit COX
• SE’s- GI, renal, CV
• aspirin- at low doses, as anti-thrombotic effects (irreversible inhibition of COX-1 in plts)- at high doses, converted to salicylates- anti-infl effects

Question 16

NSAID- managing GI intolerance

Answer 16

• switch to diff chemical class of NSAIDs
• NSAID + misoprostol (PG)
• NSAID + gastric anti-secretory agent (PPIs)- omeprazole
• switch to coxib-class NSAID

Question 17

Coxibs vs NSAID + PPI- GI safety

Answer 17

-Coxibs spare COX-1- in GI tract, COX-1 can generate PGs to maintain mucosal integrity!!

Question 18

Coxibs- complications

Answer 18

CV safety

-TxA2&raquo_space; PGI2- allows plts to aggregate

Question 19

if NSAIDs and acetaminophen are ineffective or contraindicated- alternatives

Answer 19

Anti-infl steroid:

• Triamcinolone acetonide/hexonide
• COX-2 mRNA and protein induction is repressed

Question 20

Narcotic Analgesics for OA

Answer 20

• Tramadol

- Codeine

Question 21

Narcotics- moa

Answer 21

• opioid R ligands

- mu R agonists- analgesia!!

Question 22

narcotics- SE

Answer 22

-constipation!!