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62 Cards in this Set
- Front
- Back
General mechanism of NSAIDS
(Non-steroidal anti-inflammatory drugs) |
--inhibition of PG biosynthesis
--inhibits PG synthetase (cyclooxygenase) - COX-1 and COX-2. -COX-1 is in all normal cells for homeostasis. COX-2 is induced by inflammation. |
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Major differences between NSAID analgesics and narcotic analgesics
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(1) NSAIDs have much lower maximal effects than do opiods
(2) no addiction associated w/ NSAIDs (3) free of unwanted CNS effects of the opiods (4) treat low - moderate intensity pain |
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Therapeutic Uses of NSAIDS
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Analgesic: only effective for low to moderate pain (especially pain due to inflammation). Not effective against sharp stabbing pain.
Antipyretics: Block IL-1 response in CNS so decrease body temperature in fever state. Anti-Inflammatory: can reduce the inflammation of disease but not cure the disease Others: dysmenorrhea (painful menstruation), patent ductus arteriosus, colon cancer (reduces risk). |
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List general side effects of analgesic-antipyretic and anti-inflammatory agents.
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--GI ulceration,bleeding, perforation and intolerance = most common!
--block platelet aggregation (by inhibiting thromboxane syn) --inhibit uterine motility (used to inhibit induction of labor) --analgesic abuse nephropathy (primary lesion papillary necrosis w/ secondary chronic interstitial nephritis) --hypersensitivity (asthma attacks, urticaria and angiodema, cross reactivity to all aspirin-like drugs) |
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Which two side effects of nonselective COX inhibitors are NOT shared by selective COX-2 inhibitors?
a) inhibition of platelet function b) alteration in renal funciton c) inhibition of labor induction d) GI ulceration and intolerance |
These 2 COX-1 inhibitor side effects are NOT shared by COX-2 inhibitors..
(a) inhibition of platelet function (d) GI ulceration and intolerance The other side effects (renal function inhibition and labor induction inhibition) are common to both COX-1 and COX-2 inhibitors. |
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Aspirin
--mechanism --uses --contraindications |
Aspirin - NSAID prototype
-Salicylate Mechanism: irreversible acetylation of COX. Effects on platelets persist for lifetime of platelet (8-10days) Uses: analgesic, antipyretic, anti-inflammatory (also juvenile RA, dec incidence of colon cancer & MI) Contraindications: ulcer, gout, asthma, influenza (Reye's syndrome) |
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Aspirin
--side effects --signs of intoxication |
Aspirin
SE's: tinnitus, dec renal function, GI intolerance, hypersensitivity, hepatotoxicity Salicylate Intoxication: respiratory alkalosis followed by metabolic acidosis, headache,dizziness, mental confusion, ringing in ears, drowsiness, sweating |
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Diflunisal
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Salicylic acid derivative.
-greater anti-inflammatory effect than aspirin. -No antipyretic effect -Poor penetration into CNS -Less auditory side effects than aspirin |
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Diflunisal does not have which of the following effects:
(a) anti-pyretic (b) anti-inflammatory |
(a) anti-pyretic
Diflunisal has no anti-pyretic effect but has a greater anti-inflammatory potency compared to aspirin. |
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Mesalamine
(5-aminosalicylic acid) |
Salicylate used for its local effect in the treatment of inflammatory bowel disease.
-Oral preparation (Asacol) - used for ulcerative colitis |
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This NSAID is used to treat IBD.
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Mesalamine
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Acetaminophen
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NSAID
-Tylenol -Analgesic and antipyretic but weak anti-inflammatory agent. -Well tolerated and lack many side effects of aspirin. Substitute for aspirin in pts with contraindications. -Oral absorption, half life - 1-4 hrs, >4-6 g/d are not recommeded -Adverse effects: Overdose (10-15 g/d) --> Fatal hepatic necrosis cue to toxic metabolite -Chronic alcoholics have increased risk of toxicity. |
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Of the following aspirin effects, which one is NOT shared by acetaminophen?
(a) anti-pyretic (b) anti-inflammatory (c) analgesic |
(b) anti-inflammatory
Acetaminophen is a weak anti-inflammatory drug. |
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Give this antidote within 10 hours of acetaminophen OD..
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N-acetylcysteine
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Acetaminophen can be metabolized to these 3 non-toxic metabolites
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(1) sulfate
(2) glucoronide (3) glutathione compound which is eventually converted to mercapturic acid |
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This severe adverse effect can result from acetaminophen OD.
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fatal hepatic necrosis
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TRUE or FALSE
Chronic alcoholism can increase the risk of acetaminophen toxicity. |
TRUE
Chronic alcoholism induces P-450 enzymes, which is the key player in forming a toxic metabolite that can cause hepatic necrosis. |
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Indomethacin
--uses --adverse effects --what drug inhibits indomethacin renal secretion? |
Indomethacin - NSAID
-Oral rapid/complete absorption. Half life 2-3 hrs --tx: acute gout, ankylosiing spondylitis, management of patent ductus arteriosus (inhibit PG syn because PGs are whats keeping it open) --adverse effects: GI- nausea, vomiting, anorexia, abdominal pain, CNS severe frontal headache, dizziness, confusion, depression --probenecid inhibits renal secretion of indomethacin |
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Sulindac
--uses --rare complication |
Sulindac - NSAID - Indole derivative
-Prodrug --> active metabolite -Less ulcerogenic potential, GI irritation and blood loss than aspirin -Dose: 150-200 mg twice daily. Half life 7 hrs --tx: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout suppress polyp formation in colon cancer Rare complication: renal stone |
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Tolmetin
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NSAID - heteroaryl acetic acid derivative
-Adverse effects: GI (MC) - epigastric pain, nausea, vomiting, CNS - less common than indomethacin -Ineffective in treatment of gout |
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Diclofenac
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NSAID - heteroaryl acetic acid derivative
-Reduces both synthesis of PG and leukotrienes -Oral -Less likely than aspirin to cause peptic ulcer and GI bleeding -Adverse Effects: GI (MC), Increased hepatic transaminase -Contraindications: children, nursing mothers or pregnant women |
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Ketorolac
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NSAID - heteroaryl acetic acid derivative
-First injectable NSAID -mechanism of action: related to prostaglandin synthetase inhibition -Used for short-term (<5 days) of moderately severe acute pain that requires pain relief at opioid level (w/ no addiction), used postoperatively |
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These 2 drugs can reduce the synthesis of both prostaglandins and leukotrienes.
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1) diclofenac
(2) ketoprofen These drugs inhibit both lipooxygenase and cyclooxygenase enzymes. |
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This NSAID inhibits lipoxygenase and cycloxygenase and is not recommended for children, pregnant or nursing women.
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Diclofenac
(as a comparison, ketoprofen aslo inhibits lipoxygenase and cycloxygenase) |
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This NSAID can be used short-term for moderate - severe pain.
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Ketorolac
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Ibuprofen
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NSAID - Motrin, Advil, Nuprin
-Mild anti-inflammatory and analgesic drug with reduced symptoms of gastric irritation -Highly protein bound - metabolized in liver. -Oral. Half-life 2 hours. 200 mg = OTC dose |
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TRUE or FALSE
Ibuprofen has a more potent analgesic effect compared to its anti-inflammatory effect. |
TRUE
Larger ibuprofen doses are needed to produce anti-inflammatory effects |
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Naproxen
--uses --potency --main route of elimination |
Naproxen - NSAID -Proprionic acid derivative
-Aleve, Naprosyn -Oral, Long half-life (14hrs), taken twice daily -Less GI irritation than aspirin -Crosses placenta and appears in milk of lactating women --tx: juvenile RA, acute gout, akylosing spondylitis, rheumatoid arthrits --20x more potent than aspirin --handled mainly by kidneys |
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Name the 5 NSAIDs with (relatively) long half-lives.
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(1) naproxen -- 14hr
(2) meloxicam -- 20hr (3) nabumetone -- 24hr (4) oxaprozin -- 50hr (5) piroxicam -- 55hr |
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Ketoprofen
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NSAID - Propionic acid derivative
-Inhibits both cycolooxygenases and lipoxygenases (PG and Leukotrienes) -Short half life (2hrs) take 3-4 a day -Adverse effects: GI and CNS |
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Oxaprozin
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NSAID - propionic acid derivative
-newer drug -Very long half life (40-60 hrs) -Once daily used for anti-inflammatory |
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Piroxicam
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NSAID - Enolic acid
-structurally distinct from all other NSAIDs -Very long half life (50-60 hrs) -Potent reversible inhibitor of cyclooxygenase; nonselective COX inhibitor |
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Meloxicam (Mobic)
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NSAID -Enolic acid
-Preferentially inhibit COX-2 over COX-1 (so less side effects) -Half life 20 hrs -Used for osteoarthritis |
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This NSAID is structurally distinct from other NSAIDs and has a long half life.
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Piroxicam
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This NSAID inhibits COX-2 over COX-1 and treats osteoarthritis.
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Meloxicam
(as a comparison, nabumetone also preferentially inhibits COX-2; nabumetone however is a non-acid NSAID and it is also a prodrug) |
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Nabumetone
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NSAID - alkanones
-Only nonacid NSAID -Preferentially inhibits COX-2 at low doses -Low incidence of side effects; GI ulceration much lower than other NSAIDs -Half life 24 hrs |
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This is the only nonacid NSAID. It preferentially inhibits COX-2 at low dose, but it is not purely selective.
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Nabumetone
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Nabumetone
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NSAID - alkanones
-Only nonacid NSAID -Preferentially inhibits COX-2 at low doses -Low incidence of side effects; GI ulceration much lower than other NSAIDs -Half life 24 hrs |
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Misoprostol
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Synthetic PGE1 analog
-used to prevent ulcers in people who take certain arthritis or pain medicines, including aspirin, that can cause ulcers. It protects the stomach lining and decreases stomach acid secretion. -side effect: diarrhea |
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This is the only nonacid NSAID. It preferentially inhibits COX-2 at low dose, but it is not purely selective.
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Nabumetone
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Celecoxib
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NSAID
-Selective COX-2 inhibitor -Significantly fewer ulcers than naproxon or ibuprofen -Used for osteoarthritis and rheumatoid arthritis -Does not affect platelet aggregation or prothrombin time |
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Misoprostol
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Synthetic PGE1 analog
-used to prevent ulcers in people who take certain arthritis or pain medicines, including aspirin, that can cause ulcers. It protects the stomach lining and decreases stomach acid secretion. -side effect: diarrhea |
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Abatacept
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Anti-rheumatic Drug
-selective costimulation modulator, inhibits T cell activation -used for adult RA and juvenile idiopathic arthritis -IV injection |
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Celecoxib
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NSAID
-Selective COX-2 inhibitor -Significantly fewer ulcers than naproxon or ibuprofen -Used for osteoarthritis and rheumatoid arthritis -Does not affect platelet aggregation or prothrombin time |
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Rituximab
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Anti-rheumatic Drug
-Chimeric monoclonal antibody binds specifically to the antigen CD20 B lymphocytes -IV injection -Fatal infusion reactions have been reported |
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Abatacept
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Anti-rheumatic Drug
-selective costimulation modulator, inhibits T cell activation -used for adult RA and juvenile idiopathic arthritis -IV injection |
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List the 3 TNF-alpha blocking agents.
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(1) etanercept
(2) adalimumab (3) infliximab |
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Rituximab
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Anti-rheumatic Drug
-Chimeric monoclonal antibody binds specifically to the antigen CD20 B lymphocytes -IV injection -Fatal infusion reactions have been reported |
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Etanercept
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TNFalpha blocking agent
-Antirheumatic drug -binds specifically to TNF and blocks its interaction with cell surface TNF receptors -Given SC twice weekly |
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List the 3 TNF-alpha blocking agents.
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(1) etanercept
(2) adalimumab (3) infliximab |
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Adalimumab
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TNFalpha blocking agent
-Antirheumatic drug -binds specifically to TNF and blocks its interaction with p55 and p75 cell suface TNF receptors -Given SC every other week -TB, invasive fungal infections and other infections have been seen in pts taking this |
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Etanercept
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TNFalpha blocking agent
-Antirheumatic drug -binds specifically to TNF and blocks its interaction with cell surface TNF receptors -Given SC twice weekly |
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Infliximab
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TNFalpha blocking agent
-Anti-rheumatic drug -neutralizes activity of TNFalpha by binding w/ high affinity to the soluble and membrane bound TNF alpha and inhibits binding of TNF with its receptos -Increased risk of infections Given IV every 8 wks |
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Adalimumab
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TNFalpha blocking agent
-Antirheumatic drug -binds specifically to TNF and blocks its interaction with p55 and p75 cell suface TNF receptors -Given SC every other week -TB, invasive fungal infections and other infections have been seen in pts taking this |
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Infliximab
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TNFalpha blocking agent
-Anti-rheumatic drug -neutralizes activity of TNFalpha by binding w/ high affinity to the soluble and membrane bound TNF alpha and inhibits binding of TNF with its receptos -Increased risk of infections Given IV every 8 wks |
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Inhibition of lipoxygenase prevents the formation of this molecule.
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leukotrienes
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The inducible COX-2 enzyme is involved in the formation of this molecule.
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prostaglandins
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The housekeeping COX-1 enzyme is involved in the formation of these 2 molecules.
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COX-1 involved in formation of:
(1) prostaglandins (2) thromboxane |
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Name the specific NSAID that would treat each of the following..
(1) short term moderate - severe pain (2) IBD (3) management of patent ductus arteriosus (4) suppression of polyp formation in colon cancer (5) RA without effect on prothrombin time |
(1) moderate-severe pain: ketorolac
(2) IBD: mesalamine (3) patent DA: indomethacin (4) suppress polyp formation: sulindac (5) no effect on prothrombin time: celecoxib |
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Why is adminstering N-acetylcysteine appropriate in the case of acetaminophen overdose?
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In the case of acetaminophen OD, metabolism by conjugation becomes saturated, and the drug is oxidatively metabolized by the CYP enzymes into a toxic metabolite.
N-acetylcysteine is a precursor of glutathione and as such, increases glutathione conjugation of the toxic intermediate. Thus, the toxic intermediate is converted to a glutathione-containing compound rather than a toxic adduct that causes hepatocyte apoptosis and/or liver necrosis. |
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Which 2 NSAIDs and which anti-rheumatic drug would be appropriate for treatment of juvenile RA?
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Used to treat juvenile RA:
--aspirin --naproxen --abatacept |
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Which NSAIDs would be appropriate for treatment of ankylosing spondylitis?
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Used to treat ankylosing spondylitis..
--indomethacin --sulindac --naproxen |