Term
| COX-1 is constitutive where? |
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Definition
| In most tissues, including platelets & kidney, but esp in gastric epithelium and is the major source of cytoprotective prostaglandin(? u sure its not prostacyclin) formation |
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Term
| What are COX-2 induced by? |
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Definition
| Growth factors, tumor promoters and cytokines. NB that its also the major source of prostanoids in inflammation and CA |
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Term
| Where are COX-2 constitutive? |
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Definition
| Brain and kidney, furthermore endothelial COX-2 is the primary source of vascular prostacyclins |
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Term
| What are some nonselective COX inhibitors? |
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Definition
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Term
| What are the 3 selective COX-2 inhibtors? |
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Definition
Celecoxib
Etoricoxib
Meloxicam |
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Term
| How does the analgesic axn of NSAIDs work? |
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Definition
| Decreasing PGE2 synthesis; PGE2 sensitizes nerve endings to axn of bradykinin, histamine, and other chemical mediators of inflammatory process. NB that NSAIDs are superior to opioids in regards to inflammatory pain. |
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Term
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Definition
| Infection, malignancy, etc => activate WBCs to release PGE2 -> elevates the set point of the anterior hypothalamic thermoregulatory center |
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Term
| What kind of pain is particularly controlled by NSAIDs? |
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Definition
| Inflammatory and chronic postoperative pain |
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Term
| What viscera is NSAIDs not helpful for? |
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Definition
| Hollow viscera but an exception is menstrual pain |
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Term
| What Dz process are NSAIDs approved to Tx? |
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Definition
| RA, OA, acute gouty arthitis (indomethacin), ankylosing spondylitis and dysmenorrhea |
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Term
| Which NSAIDs are not used to Tx gout and why? |
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Definition
Aspirin (& salicylates) - At low levels inhibits urate excretion, and at HIGH doses is uricosuric thus increasing risk of renal calculi. (In addition it can inhibit axn of uricosuric agents)
Tolmetin - for unknown reasons is ineffective |
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Term
| Why do pts with FAP use NSAIDs? |
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Definition
| Regular use can decrease risk of colon CA by 50% |
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Term
| How can NSAIDs be used to target the A/Es of Niacin use? |
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Definition
| Intense flushing is mediated by PGD2 |
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Term
| What closes PDA in premature infants? |
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Definition
| Indomethacin. NB that its kept open via PGE2 (...) |
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Term
| How do NSAIDs cause GI effects? |
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Definition
1) Depressing mucosal cytoprotective prostaglandins (esp PGI2 & PGE2). These were involved in inhibiting gastric acid secretion, enhancing mucosal blood flow, and promote secretion of cytpprotective mucus in the intestine
2) Local irritant |
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Term
| What is used to Tx NSAID-induced gastric ulcers? |
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Definition
| Misoprostol, PPI, H2 blockers |
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Term
| What are the RR's of each NSAID? |
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Definition
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Term
| What A/Es can NSAIDs have on a hypoperfused kidney? |
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Definition
| Since prostaglandins (PGE2 & PGI2) only play a role when the kidney is hypoperfusing, NSAID-induced decrease in PGE2 -> Na2+ & H2O retention whereas PGI2 decrease -> hyperkalemia & acute renal failure (?) |
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Term
| What is the etiology of Acute Interstitial Nephritis? |
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Definition
| MCC is antibiotic and NSAID -induced type 1 hypersensitivity whereby inflammatory cells infiltrate the interstitum |
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Term
| What is Analgesic Nephropathy? |
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Definition
| Chronic use of damaging analgesics -> renal papillary necrosis -> leading to chronic interstitial nephritis |
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Term
| Which NSAIDs show serious hematological rxns? |
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Definition
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Term
| Which NSAID is a sulfonamide? |
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Definition
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Term
| How are NSAIDs physiological antagonists to ACE inhibitors? |
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Definition
| Well Kinins stimulate prostaglandin production and ACE inhibitors prevent the breakdown of kinins, now NSAIDs come in and block the production of those vasodilators & natriuretic prostaglandins |
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Term
| What other interactions do NSAIDs have with either cortocosteroids or warfarin? |
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Definition
| With the former there is a greater frequency and severity and with the latter there is an increased risk of bleeding |
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Term
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Definition
| Kid less then 20 yo takes aspirin or some other salicylate for his fever associated with a viral illness. Instead the pts shud take acetaminophen for the antipyresis (ibuprofen can also be taken). NB that its an often fatal, fulminating hepatitis w/ cerebral edema |
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Term
| How is aspirin metabolized? |
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Definition
| Well the bodys esterases deacetylate aspirin rapidly producing salicylate (weaker and reversible) |
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Term
| What are the respiratory axns of Aspirin? |
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Definition
| At TC salicylate uncouples pxidative phosphorylation -> increasing alveolar ventilation via increased inspiration trying to fix the elevated CO2. At higher doses it works directly on the respiratory center in the medulla -> hyperventilation & respiratory alkalosis, which is compensated by the kidney. At toxic levels -> central respiratory paralysis followed by respiratory acidosis |
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Term
| How do NSAIDs prolong bleeding time? |
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Definition
| By inhibiting platelet aggregation via irreveribly inhibiting TXA2 production when PGI2 is only reversibly affected |
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Term
| What are the CVS applications for NSAIDs? |
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Definition
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Term
| Are salicylates always anti-inflammatory? |
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Definition
| Nope only at higher doses. NB the other dosing regeims |
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Term
| Descripe the metabolism of aspirin? |
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Definition
Hydrolysed to salicylate & acetic acid by esterase in tissue and in blood. At low doses (<300mg), salicylate is mainly converted by liver to hydrosouluble conguates (with glycine & glucuronate) that are rapidly excreted by kidney, resulting in elimination with first-order kinetics & a T1/2 of 3.5 hrs
When the dose if >1g, conguation enzymes become saturated and zero-order kinetics is observed |
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Term
| When shud aspirin be avoided? |
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Definition
| NB that a single 325mg dose of aspirin doubles the mean bleeding time of a normal person for 4-7 days. So in pts with severe hepatic damage, hypoprothrombinemia, vit. K def or hemophilia, dont take it. Even in pts for surgery, stop taking it a wk before |
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Term
| Explain hypersensitivity to NSAIDs? |
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Definition
| Increased biosynthesis of leukotrienes cause of the diversion of arachidoniate to lipoxygenase metabolism as a result of COX inhibition |
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Term
| Comment on the uricosuric effects of aspirin? |
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Definition
Uric acid uses the same transport system as anionic drugs (aspirin, sulfinpyrazone, probenecid)
Low dose aspirin - decrease uric acid secretion (less in pee)
high dose aspirin - decreased uric acid reabsorption (more in pee) |
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Term
| What are some hepatic effect of saliylate? |
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Definition
| In pts with connective tissue disorders, with several months Tx there maybe asymptomatic increase in serum hepatic transaminases, thus contraindicated in pts w/ chronic liver Dz |
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Term
| What abt aspirin use in preg? |
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Definition
| C in 1st and 2nd trimester but a D in the 3rd |
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Term
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Definition
| mild chronic salicylate intox. Syndrome includes: headache, dizzy, tinnitus, diff hearing, dim vision, mental confusion, lassitude, drowsy, sweating, thirst, hyperventilation, N/V/D |
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Term
| Severe intoxication of salicylates is seen as? |
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Definition
Acutely as respiratory alkalosis & metabolic acidosis
Chronically leads to depression of medulla (respiratory depression and vasomotor deprssion -> circulatory collapse). COD is respiratory failure |
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Term
| Do COX 2 inhibitors have a caridoprotective axn? |
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Definition
| No as they have no impact on platelet aggregation |
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Term
| Why would u have renal toxicity with COX-2 inbitors? |
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Definition
| Cause they are constitutively express there |
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Term
| Why would someone say that COX-2 inhibitors be said to have a thrombotic event? |
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Definition
| COX 1 mediates synthesis of TXA2 in platelets leading to aggregation and COX 1 & 2 in the endothelium via PGI2 inhibit this aggregation, thus when u use COX 2 selective inhibitors u leave the platelets to aggreagate and knock out the PGI2 from the endothelium |
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Term
| What are the COX 2 inhibitors? |
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Definition
Currently celecoxib is the only one in USA, Rofecoxib & valdecoxib have be withdrawn cause of their prothrombotic effects. Etoricoxib is a second generation COX 2 inhibitor with the highest selectivity ratio of any coxib for COX 2 BUT not available in USA.
Meloxicam prefers COX 2 over COX 1 but is not selective as coxibs |
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Term
| How is acetaminophen different from NSAIDs? |
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Definition
| Acetaminophen has no anti-inflammatory or anti-platelt effects. Furthermore it doesnt affect uric acid levels as it acts more centrally thus can even be used in pts w/ hemophilia of peptic ulcer or bronchospasm precipitated by aspirin. Furthermore cause it lacks the peripheral effect of aspirin it can be used along with probenecid to Tx GOUT |
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Term
| What is the DOC for Tx-ing short-term fever and minor pain during pregnancy? |
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Definition
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Term
| What is the A/E associated with acetaminophen OD? |
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Definition
| Dangerous hepatotoxin, antidote is the inhalant acetylcysteine, a sulfhydryl donor |
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