Podiatry Boards Part 2
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NSAIDS are weak acids or bases?
What NSAIDs are Prodrugs that must be converted in the Liver Cytochrome P450?
What NSAID is totally elminated thru the biliary tract?
Sulindac and Indomethacin
Most NSAIDs are excreted thru what?
What is the problem with renal failure pts and NSAIDs?
The metabolites can accumulate and be reabsorved.
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.
What is the MOA of NSAIDs?
- Analgesic, antipyretic, anti-inflammatory
- Inhibition of Prostaglandin synthesis by inhibiting COX
What is the affect of prostaglandins?
- Raise set point of hypothalamic temps
- Bradykinin, histamine causing vasodialation and edema
Where is COX 1?
Expressed in most tissues of GI, kidneys and blood vessels
Where is COX 2?
Has less side effects if blocked
What are teh NSAIDs that are selective COX2?
Nabumetone, Celebrex, Vioxx
Where are most NSAID ulcers?>
- Antrum and stomach
- H. pylori is in the duodenom
MC side effect of NSAID is?
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)
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
What NSAIDs are less harsh on the GI and kidney?
- Nabumetone- Selective COX2
- Choline Magnesium Salicylate
- Celebrex- COX2 inhibitor
What do prostaglandins do at the kidneys?
- Regulate vascular tone
- Maintain GFR
- Enhance sodium and water excretion
- Stimulate Renin secretion
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
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
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
- Hemolytic anemia
What is the affect of NSAIDs on the liver?
- May increase liver problems if they already exist
- Diclofenac can be heptotoxic
What can NSAIDs do to the CNS?
- Headaches- vasoconstriction secondary headache (Indomethacin)
NSAIDs may cause damage to cartilage?
Some studies say yes by inhibiting hyaluronic acid and glycosaminoglycans
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 excretion
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