NSAIDs Flashcards
1. Describe the mechanism of action of aspirin, list its major side effects and signs associated with overdose, describe the treatment of aspirin overdose, and list the contraindications to the use of aspirin 2. Describe the major differences in duration of action, key uses and key side effects of aspirin, salicylic acid, diflunisal, indomethacin, ketorolac, ibuprofen, naproxen, meloxicam and celecoxib. 3. Describe the mechanism of action and special considerations for the use of colchicin
major sites of COX-1 that can result in NSAID toxicity
platelets, blood vessels, stomach, kidney
expressed during inflammation
Cox-2
typical NSAID theraputic uses
analgesic, anti-inflammatory, antipyretic
decrease the pain threshold
prostaglandins
mediate edema response
PGE2/PGI2
ways NSAIDS reduce inflammation
inhibit PGE2/PGI2 and reduce neutrophil migration
alters body temp set point
PGE2
clinical uses of NSAIDS
Pain, primary dysmonorrhea, Joint inflammation, fever
GI Side effects of NSAIDS
distress, damage, bleeding
way that NSAIDS increase stomach acid
inhibit PGE2/PGI2 which normally inhibit the H+/K+ ATPase, and increase bicarb production in the paritel cells. This leads to more proton release and less buffering
renal side effects of NSAIDS
fluid retention , decresed sodium excretion, decreased GFR, instersitial nephritis
How NSAIDS can increase bleeding
in pts with reduced clotting factors, TXA2 may be needed more to clot - NSAIDS reduce TXA2
ways NSAIDS can increase BP
reduces PGI2, which oppose vascular contractions. inhibition of COX-1/2 decreases Na+ and H2O excretion
salicylate prototypes (3)
asprin, aslicylic acid, difunisal
Acetic acid derivitaves (2)
indomethacin, ketorolac
proprionic acid derivitives (2)
ibuprophen, naproxen
enolic acid derivtive
meloxicam
COX-2 selective inhibitor
celecoxib
MOA of salicylates
binds to COX irreversably, alters ratio of PGI2/TXA2 in vasculature
Sx of salicylate toxicity
theraputic doses: GI bleedin, decreased uric acid excretion, hypersenstivy reactions
mild intox (salicylism): tinnitus, vomiting, vertigo, hyperventalation due to resp alkalosis
moderate tox: increased metabolic rate, fever, metabolic acidosis
severe tox: resp depression, dehydration, come, organ failure
theraputic dose of salicylate
2-4 g.day
lethal dose of salicylate
160 g/day
tx for salicylate tox
1) cool, rehydrate, correct acid.base imbalances
2) prevent further absorption via emesis and lavage
3) alkalinize urine
4) hemodyalsis
5) diazepam for convulsions
Contraindications for salicylates
renal disease, bleeding disorders, gout, young kids, 3rd trimester preg
advantages of naproxen
long t 1/2, intermediate potency
most potent NSAID
indomethacin
uses of indomethacin
acute gout, arthritis, closing PDA
SE of indomethacin
GI distress and aplastic anemia
IV NSAID often uses with opiate
ketoralac
partially selective COX-2 inhbitor used fir RA and OA in adults
meloxicam
reason most COX-2 inhibitors taken off market
high risk of CV events
population that is advised not to take non-asprin NSAIDS at all
people with known CV disease
triggers inflamation in gout
granulocytes trying to remove urate crystals in joints
DOC for acute gout
colchicine
MOA of colchicine
inhibits release of chemotactic and inflammatory factors
disadvantage of colchicine
highly toxic - very low TI
side efects of colchicine
n/v, diarrhea
DOC for prevention of gout
probenecid and sulfinpyrazone, allopurinol, feboxustat
MOA of probenecid and sulfinpyrazone
inhibits renal reabsorption of urate
MOA of allopurinol
suicide inhibitor of xanathine oxidase - blocks urate synthesis
SE of allopurinol
GI irritation and skin reactions, inhibits other enzymes in purine pathway
febuxostat MOA
nonpurine inhibitor of xanthine oxidase - blocks urate synthesis
SE of febuxostat
liver tox and GI irritation
