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NSAIDS are weak acids or bases?
Acids
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What NSAIDs are Prodrugs that must be converted in the Liver Cytochrome P450?
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What NSAID is totally elminated thru the biliary tract?
Sulindac and Indomethacin
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Most NSAIDs are excreted thru what?
Kidney
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What is the problem with renal failure pts and NSAIDs?
The metabolites can accumulate and be reabsorved.
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How do NSAIDs get to inflamed tissue?
The acidity of inflamed synovial tissue allows for increase penetration into joints and a larger portion of the unbound drug in synovial fluid. This concentration will remain constant.
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What is the MOA of NSAIDs?
- Analgesic, antipyretic, anti-inflammatory
- Inhibition of Prostaglandin synthesis by inhibiting COX
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What is the affect of prostaglandins?
- Raise set point of hypothalamic temps
- Bradykinin, histamine causing vasodialation and edema
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Where is COX 1?
Expressed in most tissues of GI, kidneys and blood vessels
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Where is COX 2?
Has less side effects if blocked
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What are teh NSAIDs that are selective COX2?
Nabumetone, Celebrex, Vioxx
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Where are most NSAID ulcers?>
- Antrum and stomach
- H. pylori is in the duodenom
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MC side effect of NSAID is?
GI
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Why the GI and how to prevent?
- It increases the acid production and decreases mucous production by decreasing Prostglandins in the gut (which increase bicarb and mucous production for protection)
- Take NSAIDs with food
- They have enteric coated NSAID= Naproxen (Alieve)
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What are some cytoprotective agents?
- Protect the GI:
- Misoprostol (Cytotec)
- H2 antagonist (Cimetidine, Ranitidine, Famotidine) which block release of histamine from parietal cells
- Sucralfate (Carafate) Neutralize stomach acids
- Prilosec- H2 blocker
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What NSAIDs are less harsh on the GI and kidney?
- Nabumetone- Selective COX2
- Etodolac
- Choline Magnesium Salicylate
- Salsalte
- Celebrex- COX2 inhibitor
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What do prostaglandins do at the kidneys?
- Regulate vascular tone
- Maintain GFR
- Enhance sodium and water excretion
- Stimulate Renin secretion
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What prostglandin affects the lungs?
- PGE2 is a bronchodilator and stabilizes histamine stores in mast cells- Block this and get bronchospasms
- Can affect Leukotriene production also (LOX)
- Leukottrienes can cause bronchoconstrictions
- NSAIDs that may block LOX and COX are better for pts with pulmonary problems
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NSAIDs may block COX but then increase production of LOX. What is the affect of leukotrienes on the heart?
LTD4 causes vasocontriction, must be careful giving an NSAID
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What can NSAIDs do to the blood?
- Impair platelet aggregation by inhbiting thromboxane A2 but is reversible (Unlike ASA)
- NSAIDs should be discontinued before sx because of this 4-5 days before, ASA 8-12 days and Piroxicam 8-10 days
- Another problem is blood dyscrasis
- Aplastic anema
- Agranulocytosis
- Hemolytic anemia
- Thrombocytopenia
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What is the affect of NSAIDs on the liver?
- May increase liver problems if they already exist
- Diclofenac can be heptotoxic
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What can NSAIDs do to the CNS?
- Headaches- vasoconstriction secondary headache (Indomethacin)
- Tinnitus
- Confusion
- Irritability
- Dizzy
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NSAIDs may cause damage to cartilage?
Some studies say yes by inhibiting hyaluronic acid and glycosaminoglycans
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What can NSAIDs do to other drugs that are bound to proteins?
- Kick them off
- It can displace Warfarin and increase the active free form
- Increase valproic acid and phenytoin (Antiepileptics)
- Increase sulfonylureas cause hypoglycemia
- Anatgonize antihypertensives b/c they inhibit Na and water excretionÂ
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