| A | B |
|---|
| indomethacin | very potent COX inhibitor, high degree of side effects with chronic use |
| indomethacin indications | Ob/Gyn use: suppress uterine contractions closure of patent ductus arteriosus |
| sulindac | NSAID pro-drug, needs metabolic activation |
| aspirin MOA | irreversible inhibitor of COX-1 and COX-2, covalent modification of enzyme (acetylation of ser residue) |
| asprin toxicity | tinnitus, uncouples oxidative phosphorylation |
| asprin drug interactions | low dose blocks actions of probenecid, high dose uricosuric |
| Other salicylates | Mesalamine,sulfasalazine,osalazine |
| Mesalamine metabolism | no oral bioavailability, given as suppository) |
| Mesalamine indications | inflammatory bowel disease/ rheumatoid arthritis |
| diflunisal therapeutics | poor CNS penetration, no anti-pyretic effect |
| diflunisal indications | potent anti-inflammatory action |
| acetaminophen | P450 N-hydroxylation generates reactive metabolite |
| acetaminophen | not a good inhibitor of COX in presence of reactive oxygen species—superoxide, peroxide, alkoxy radicals found in inflammatory lesions |
| acetaminophen | analgesic, anti-pyretic, not anti-inflammatory |
| Reacts with protein sulfhydryl groups | acetaminophen |
| acetaminophen | antidote: N-acetylcysteine |
| commonly used in children, children have less conjugation metabolism | acetaminophen |
| celecoxib, rofecoxib, and valdecoxib problems: | valdecoxib problems: |
| Lack of anti-platelet effects and inhibition of COX-2 in vascular endothelial cells results in unfavorable TxA2 vs. PGI2 ratio | celecoxib, rofecoxib, and valdecoxib problems: |
| High expression of COX-2 in kidney, decreased biosynthesis of renal prostaglandins | celecoxib, rofecoxib, and valdecoxib problems: |
| no inhibition of constitutive COX-1 in GI tract | celecoxib, rofecoxib, and valdecoxi |
| new highly selective COX-2 inhibitors thus, good anti-inflammatory action with low GI side effects | celecoxib, rofecoxib, and valdecoxib |
| nabumetone | pro-drug, somewhat selective inhibition of COX-2 |
| piroxicam | COX inhibitor, inhibits neutrophil activation in the presence of PGs may inhibit proteoglycanase and collagenase in cartilage long half-life - - 50 hrs |
| meloxicam | somewhat selective effect on COX-2 inhibition |
| fenoprofen, flurbiprofen | similar to other members of the ibuprofen class |
| oxaprozin | NSAID, unusually long half-life - - 40 to 60 hrs uricosuric |
| ketoprofen | in addition to COX inhibition, stabilizes lysosomal membranes and may antagonize bradykinin actions |
| naproxen | 20 times more potent than aspirin, similar (to aspirin and other NSAIDs) in incidence of GI adverse effects |
| diclofenac | very potent COX inhibitor, may reduce release and/or uptake of arachidonic acid |
| diclofenac | can be formulated with misoprostol to reduce GI toxicity |
| ketorolac | used to treat post-op pain as alternative to opiates, can be given IM |
| potent analgesic, weak anti-inflammatory | ketorolac |
| history of use in pediatric populations, well tolerated | tolmetin |
| mefenamic acid and meclofenamate | not recommended as initial therapy of arthritis, may antagonize prostaglandin effects |
| mefenamic acid and meclofenamate | analgesic, tx of arthritis |
| etodolac | large difference between anti-inflammatory dose and dose which blocks GI prostaglandin biosynthesis |
