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Aspirin (acetylsalicylic acid: ASA)
- Analgesic, anti-inflam, anti-pyretic, antithrombotic
- Irrev inhibit COX thru acetylation (170:1 COX1:2)
- Salicylic acid (metabolite) inhibits PG synth - majority of anti-inflam effects
- SE: GI effects - nausea, vomiting, dyspepsia, heartburn, ulcers; bleeding; inhibition of uric acid secretion@renal tubule
- Salicylicism: hyperthermia, hearing loss, tinnitus!
- Low doses to block platelet aggregation, intermediate for antipyretic/analgesic, high dose for anti-inflamm
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Celecoxib
- selective COX2, increased PG synth
- analgesic, effective in hyperalgesia
- TxA2 is produced by COX1 in platelets = does not inhibit platelet aggregation!
- SE: risk dependes on duration of use; cardio SE, GI bleeding, ulceration, perforation
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Diclofenac
- IM, rapid action
- blocks arachidonate binding
- analgesic, antipyretic, anti-inflamm
- preferential COX2
- SE: similar to others, hepatotoxicity
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Ibuprofen (advil, motrin, nuprin)
- similar profile to ASA
- SE: GI effects < ASA
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Indomethacin
- More potent anti-inflam, same as ASA for analgesia, nonselective
- PO, R, IV
- For severe rheum arthritis, OA, acute gouty arthritis, ankylosing spondylitis
- SE: similar to ASA but more severe
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Ketorolac
- nonselective, comparable to morphine in analgesia w/less drowsiness, nausea, vomiting
- PO, IV, opth, IM
- SE: dosing restriction <5d due to incr. SE
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Naproxen (aleve, naprosyn)
- nonselective
- 1/2life 12-17h compared to ibuprofen (2h)
- SE: GI effects less than ASA, indomethacin
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Sulindac
- nonselective
- OA, RA, ankylosing spondylitis, bursitis, acute gouty arthritis
- w/celecoxib, only NSAID for regression of colorectal polyps w/familial adenomatous polyposis
- GI: same for ASA
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Meloxicam
- less selective for COX2 than celecoxib
- SE: same as ASA
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acetaminophen
- NOT NSAID! non-opioid analgesic
- better for pts w/underlying renal disease
- COX2 inhibitor, does not inhibit in periphery, no anti-inflamm!
- SE: excess = hepatotoxicity, otherwise less than ASA
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Prostagladins in inflammation
- PGI2: inhibits platelet aggregation, vasodilatation, vascular permeability (edema)
- PGE2: pain, hyperalgesia, heat, vasodilatation, bronchoconstriction, synergistically act with other pro-inflammatory mediators (histamine, complement, LTB4)
- TXA2: promotes platelet aggregation, vasoconstriction, bronchoconstriction.
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Drug interactions
- Displace other drugs from plasma protein binding sites:− Anti-coagulants (warfarin): Bleeding risk greatly increased − Phenytoin: (increased CNS toxicity, difficulty dosing) − Oral Hypoglycemics: (increased hypoglycemic risk) − Methotrexate: (increased toxicity)
- Anti-Hypertensives (diuretics, beta blockers, ACE inhibitors): NSAIDs may blunt the anti-hypertensive effects and cause renal decompensation or renal failure in patients receiving these drugs
- Methotrexate, digoxin, aminoglycosides, lithium: NSAIDs inhibit clearance
- Probenecid: renal clearance of NSAIDs reduced by probenecid
- Antacids: absorption of some NSAIDs inhibited by antacids
- Aspirin: may lower levels of other NSAIDs, but side effects are additive
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Half life comparison
- Short Half Life (< 6 hours): more rapid effect and clearance Aspirin (0.25-0.33 hrs), Diclofenac (1.1 ± 0.2 hrs), Ketoprofen (1.8 ± 0.4 hrs), Ibuprofen (2.1 ± 0.3 hrs), Indomethacin (4.6 ± 0.7 hrs)
- Long Half Life (> 10 hours): slower onset of effect and slower clearance Naproxen (14 ± 2 hrs), Sulindac (14 ± 8hrs), Namebutone (26 ± 5 hrs), Piroxicam (57 ± 22 hrs) (also COX-2 Selective Inhibitors)
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Treatment of acetaminophen toxicity
N-acetylcysteine
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Discontinuation / Avoidance of NSAIDs
- Take medication with meal
- Pharmacologic − H2 Receptor Antagonists (high doses of ranitidine) − PPIs (omeprazole)
- − Misoprostol (PGE 1 analog) which restores cytoprotective effects)
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NSAIDs in patients w/renal compromise
- PGE2, PGI2 help vasodilate to maintain renal function
- acute renal failure caused by decr. GFR
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