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31 Cards in this Set
- Front
- Back
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Dysmenorrhea
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Caused by prostaglandin production in uterine smooth muscle leading to painful muscle cramping.
Aspirin is ineffective, but ibuprofen, naproxen and other NSAIDs are widely used |
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Bartter's syndrome
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Results from overproduction of renal prostaglandins
NSAIDs (other than aspirin) are effective |
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Patent Ductus Arteriosus
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PGs are involved in maintaining patency of ductus. NSAIDS (indomethacin, ibuprofen) have been given to effect closure.
Care should be taken about using these durgs at near-term pregnancy |
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Acute gouty arthritis
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Treat with NSAIDs (not ASA)
Mechanism is unknown |
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Familial Adenomatous Polyposis (FAP) and colorectal cancer
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NSAID use was associated with reduced formation of polyps and cause regression of polyps.
Mechanism is uncertain |
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NSAID effect on GI
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Causes gastric and duodenal lesions by:
Direct irritation of mucosa Inhibition of PG synthesis (particularly PGI2 and PGE2). Cox-1 constitutively expresses PGI2 and PGE2 in the GI tract, which activates the prostaglandin EP3 receptor to reduce gastric acid secretion. Blocking Cox-1 will results in excessive gastric acid production Cox-1 inhibition contributes to decreased mucus production, decreased HCO3- secretion, and impaired mucosal proliferation (all part of the mucosal defense system) PGE2 and misoprostol (PGE1 analog) alleviate some of the symptoms |
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NSAID effects on kidneys
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Renal cortical eicosanoids, particularly prostacyclin, are required to increase renal blood flow and contribute to the maintenance of adequate glomerular filtration rate. As a consequence, administration of NSAIDs to patients with compromised renal function, either due to intrinsic renal disease, or due to pre-renal azotemia (e.g., congestive heart failure), may result in the precipitation of acute renal failure.
Clinically, NSAID-induced renal failure produces oliguria and hyperkalemia out of proportion to renal failure. Additionally, NSAID-induced renal failure is often associated with a low fractional excretion of sodium (relatively unusual in acute renal failure). |
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NSAID effect on lungs
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NSAIDs cause bronchoconstriction in 10% of asthmatics.
Both constrictor and dilator (including PGE2) substances in the bloodstream are normally acting upon the smooth muscle of the bronchus. NSAIDs decrease the amount of this dilator substance resulting in a greater effect of the remaining constrictor substances. Cause 2 is the concept of substrate switching. Since both COX and the 5-lipoxygenase share arachidoante as a substrate, inhibition of COX might provide additional substrate to the LO pathway. This increases the synthesis of LTC4 and LTD4 which are both potent bronchoconstrictor substances. |
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NSAIDs and heart surgery
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NSAIDs inhibit platelet aggregation and use post-surgery reduced MI, stroke, renal failure, and bowel infarction
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NSAIDs and parturition
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Prolongs the delivery process
Prostaglandins E and F series are uterotropic; biosynthesis by the uterus increases in hours prior to parturition from induction of COX-2 expression. |
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Salsalate (Disalcid)
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An ester of two salicylic acid molecules which is hydrolyzed in the small intestine or plasma to salicylic acid. This compound produces less GI irritation than aspirin. It does not significantly antagonize platelet function as it is only a weak cyclooxygenase inhibitor. It is commonly used in collagen vascular diseases.
A salicylate which lacks acetyl groups, is weaker (than aspirin), reversible, inhibitors of COX. Despite this difference, it possess potent anti-inflammatory and analgesic properties. salsalate - two salicylic acid molecules salsa dancing late because their stomachs are not upset (decrease GI toxicity) SALSA ironically causes less GI irritation. |
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Mesalamine
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This salicylate is used in the treatment of inflammatory bowel disease and exert their effects without being absorbed systemically.
Good for "Messy" diarrhea (IBS) |
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Sulfasalazine
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This salicylate is used in the treatment of inflammatory bowel disease and exert their effects without being absorbed systemically.
Sulfasalazine is a salicylate derivative that is cleaved into its active component by bacteria in the colon where it acts. -SULFAsalazine is activated in the colon (stinky sulfa smell). |
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Bismuth subsalicylate
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The active ingredient in Pepto-Bismol, it is used as a source of bismuth in the treatment of H. pylori-associated peptic ulcer disease
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Diflunisal
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Marketed as Dolobid, it is a difluorophenyl derivative of salicylic acid. It is a competitive inhibitor of COX and is used as an analgesic.
that flusy is celebrating with both COXes! "Di"--> competitively inhibits both COX enzymes, "Flun"--> Flunks, because it was so busy competing with the COX's that it had to copy off of someone else for the exam and got caught (derivative of aspirin...sort of a copy...), "Sal" --> it is an analgesic (salve) |
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Acetaminophen toxicity
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The principal toxicity is hepatic. Large doses of acetaminophen predisposes to the formation of large amounts of N-acetyl-benzoquinoneimine, which reacts with, and depletes, glutathione. In the absence of glutathione, the reactive metabolite binds covalently to hepatocyte macromolecules leading to dysfunction of enzyme systems. This can lead to irreversible hepatic necrosis. Evidence of hepatic damage can be delayed for several days. Laboratory evidence of acetaminophen-induced liver damage includes elevations in plasma aminotransferases, bilirubin and prothrombin time. Pathological specimens reveal centrolobular necrosis. Treatment is the sufhydryl compound, N-acetylcysteine (Mucomyst), which repletes intracellular glutathione levels. This antidote should be administered within 10-36 hours after acetaminophen ingestion.
Other toxic effects include renal tubular necrosis, hypoglycemic coma, and hypersensitivity reactions. No effects on cardiovascular, and respiratory systems. No effects on acid-base balance. |
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Indomethacin (Indocin)
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A non-selective COX inhibitor that is not commonly used as antipyretic or for acute inflammation. Still used by some to treat rheumatoid arthritis, acute gouty arthritis, and ankylosing spondylitis. Also treatment of patent ductus arteriosus and as a tocolytic agent in suppressing pre-term labor.
It frequently produces CNS side effects including headache, dizziness, confusion, depression, psychosis, and hallucinations. In addition, there are the usual GI side effects, and impaired platelet function. IndOMEthacin I=for Immune disease O=for Open ductus ME=for just "me" for now (suppresses preterm labor) |
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Ibuprofen (Motrin, Rufen, Advil, Nuprin)
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NSAID
Approved for rheumatoid arthritis, osteoarthritis, analgesia, dysmenorrhea and fever; patent ductus arteriosus. |
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Sulindac (Clinoril)
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NSAID. Approved for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis. This is a prodrug which is metabolized to the active sulfide form. The sulfide is excreted in the bile and then reabsorbed from the intestine (enterohepatic circulation). Enterohepatic cycling prolongs the duration of action o 12-16 hours.
It causes little direct GI irritation. But its other toxicities are characteristic for non-selective COX inhibition. Sulindac is still in duct (bile duct and the general vicinity) - has a longer duration of action due to enterohepatic cycling |
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Diclofenac (Voltaren)
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NSAID
Approved for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dysmenorrhea, analgesia and fever. It is a potent non-selective COX inhibitor |
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Ketorolac (Toradol)
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Approved only for analgesia, although it has typical NSAID properties (antipyretic, antiinflammatory). Given IM or IV as an analgesic post-surgery. Equivalent to morphine, 10 mg, or meperidine 100 mg. Advantage is that it is not associated with tolerance, respiratory depression or withdrawal effects. Can be used orally as an analgesic, but only for a limited time (5 days) because of GI and renal toxicity. It also inhibits platelet aggregation. It is a non-selective COX inhibitor.
"lacs" the tolerance and withdrawal effects of morphine but has GI and renal toxicity. Use post-surgery. -After TOe surgery, I want ketolorac, especially because it lacks tolerance, resp depression, and withdrawal. |
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Celecoxib
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COX-2-selective drugs are marketed for inflammatory conditions in individuals who are at risk for the GI toxicity of non-selective NSAIDs or who are intolerant to non-selective NSAIDs.
Specific COX-2 inhibitor, less specific than rofecoxib There is a slight indication that the COX-2 selective drugs may increase the risk of hypertension and thrombotic events in some patients. The frequency of renal effects seems to be similar to other members of the NSAID group. Selective COX-2 inhibitors decrease production of PGI2 but not TXA2, suggesting that they could have a prothrombotic effect. Recent studies have raised concerns that selective COX-2 inhibitors may increase the risk of thrombotic cardiovascular events |
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Rofecoxib
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Selective Cox-2 inhibitor, removed from the market due to concerns that it increases the risk of thrombotic CV events
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N-acetylcysteine (Mucomyst)
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Treatment for acetaminophen overdose associated liver disease.
Large doses of acetaminophen predisposes to the formation of large amounts of N-acetyl-benzoquinoneimine, which reacts with, and depletes, glutathione. In the absence of glutathione, the reactive metabolite binds covalently to hepatocyte macromolecules leading to dysfunction of enzyme systems. This can lead to irreversible hepatic necrosis. N-acetylcysteine (Mucomyst) repletes intracellular glutathione levels. This antidote should be administered within 10-36 ours after acetaminophen ingestion. acysts (assists) with liver N-ecrosis from ACETaminophen |
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Misoprostol
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An oral PGE1 analog, misoprostol, reduces the incidence of NSAID-induced gastric ulceration, and misoprostol is more effective in preventing both duodenal and gastric ulcers than H2-receptor antagonists. However, use of misoprostol is associated with diarrhea in up to 30% of patients, which may limit its clinical utility.
Miso soup is good for the stomach -- unless it gives you diarrhea. |
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Sodium salicylate
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A salicylate which lacks acetyl groups, is weaker (than aspirin), reversible, inhibitors of COX. Despite this difference, it possess potent anti-inflammatory and analgesic properties.
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Mechanisms of Actions of Salicylates and Other NSAIDs:
Cyclooxygenase inhibition |
Aspirin, ibuprofen, indomethacin and many others
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Mechanisms of Actions of Salicylates and Other NSAIDs:
Inhibition of NF-kB |
Sodium salicylate
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Mechanisms of Actions of Salicylates and Other NSAIDs:
Inhibition of PPAR-delta |
Sulindac
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Mechanisms of Actions of Salicylates and Other NSAIDs:
Shedding of L-selectin |
Aspirin, ketoprofen, indomethacin
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Aspirin: Unique features
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1. Irreversible inhibitor of COX
2. useful in secondary prevention of MI/stroke 3. useful in primary prevention of MI/stroke 4. useful in the immediate post-surgical period after CABG 5. associated with Reye's syndrome |
