NSAIDs Flashcards
common mechanisms of NSAIDs
inhibit COX, which blocks formation of prostaglandins, thromboxane A2
function of PGI2
vasodilation, inhibits platelet aggregation
function of TXA2
vasoconstriction, platelet aggregation
function of PGI2 and PGE2
decrease gastric acid secretion; lower pain threshold
function of PGE2 and PGF2
contract uterine smooth muscle
major sites of COX1 expression (which could result in toxicity of NSAIDs)
platelets, kidneys, blood vessels, stomach
when is COX2 expressed vs when COX1 is expressed?
COX2 expression is induced during inflammation; COX1 expression on nearly every cell
how do NSAIDs produce analgesia?
by blocking production of prostaglandins, which lower pain threshold. effective against mild to moderate dull, aching pain; act synergistically with opiates
how do NSAIDs produce anti-inflammatory effects?
reduce edema by bocking PGE2, PGI2; reduce pain; high concs of NSAIDs reduce neutrophil migration
how are NSAIDs antipyretic?
PGE2 alters body temp set point, so it blocks production of PGE2
clinical uses of NSAIDs
pain, primary dysmenorrhea, joint inflammation, fever
why is GI distress, damage, bleeding a common side effect of NSAIDs?
PGs help secrete mucous, bicardonate, H+ to protect the stomach from acid. NSAIDs decrease PG levels, so overtime the stomach acid causes pain and bleeding ulcers
common renal side effects of NSAIDs
fluid retention (increased AHD activity), decreased sodium excretion, decrease GFR, interstitial nephritis
common vascular side effects of NSAIDs
prolonged bleeding time and hypertension in sensitive patients.
contraindications of NSAIDs
px with reduced clotting factors, where TXA2 plays an important role in clotting; px with atheroschlerosis, where PGI2 plays an important role in opposing constriction (because NSAIDs increase bleeding and blood pressure)
salicylate NSAIDs
aspirin, diflunisal
acetic acid derivative NSAIDs
indomethacin, ketorolac
proprionic acid derivative NSAIDs
ibuprofen, naproxen
enolic acid derivative NSAIDs
meloxicam
COX2 selective NSAID
celecoxib
mechanism of action of salicylates (aspirin)
binds to COX irreversibly!; alters ratio of PGI2:TXA2 in the vasculature (decreases TX over time)
describe what happens to TXA2 and PGI2 in an endothelial cell after a dose of aspirin
inhibits endothelial and platelet COX; level of TX decreases permanently for the 21 day life of the platelets. endothelial cells regenerate AA and PGI in a couple hours.
to reduce the chance of a 2nd MI, a px must..
take a low dose aspirin once every day
PCKNs of aspirin/salicylates
rapidly metabolized to salicylic acid (T1/2=15 mins); salicylic acid is active/has T1/2 of 3-4 hours
1st order at low dises, 0 order at high doses
decrease of pH increases distribution
symptoms of mild intoxication of aspirin (and how many grams?)
6-7 g: tinnitus, vomiting, vertigo, hyperventilation (resp alkalosis)
symptoms/dose of moderate aspirin toxicity
8-10 g; increased metabolic rate, fever, metabolic acidosis
symptoms/dose of severe aspirin toxicity
20-50 g: respiratory depression, higher free conc of drug, acid/base probs, dehydration, loss of electrolytes, coma, renal and resp failure
treatment for salicylate intoxication
cool, rehydrate, correct electrolyte imbalance, prevent further absorption (emesis), alkalinize the urine to increase excretion (bicarb, or sodium citrate), hemodialysis, diazepam for convulsions
contraindications of aspirin
px w/ renal disease, bleeding disorders, hypersensitivity, gout, young child after viral infection (reyes syndrome), use w/ caution during 3rd trimester
properties of ibuprofen (proprionic acid derivative) at low doses vs high doses
low dose: more effective analgesic
high dose: anti-inflammatory activity as effective as aspirin
half life of naproxen (proprionic acid deriv)?; potency?
long T1/2: 13 hr
intermediate potency
most potent NSAID
indomethacin (acetic acid deriv)
clinical uses of indomethacin
acute gout, spondylitis, osteoarthritis, ductus arteriosus
NSAID that can be given IM or IV (orally and IV)/ clinical use?
ketorolac; short-term pain management
half life of meloxicam/ what’s its more selective for / clinical uses
20 hr
COX2
osteoarthritis, RA
why do selective COX2 inhibitors (celecoxib) have a health advisory?
they also have some selective inhibitor activity against PGI2 synthase; increased incidence of CV events
studies show that non-aspirin NSAID use..
increases the incidence of arial fib and increases recurrent MI; even short-term use is not advised in px with known CV disease
what is gout caused by? what triggers the inflammation?
metabolic disorder characterized by hyperuricemia and deposition of monosodium urate in joints; inflammation triggered by action of granulocytes trying to remove the urate crystals
drugs for acute treatment of gout
colchicine, indomethacin
colchicine-highly toxic but good for acute attacks; nausea, vomiting, diarrhea
drugs for prevention of gout
probenecid (urate diuretic) inhibits renal tubular reabsorption of urate
allopurinol (XO inhibitor) blocks urate synthesis by suicide inhibition of XO
side effect of uricosuric agents and XO inhibitors
can cause acute gout attack when crystal begin to break up
to avoid this, use 1-2 weeks after an acute attack and combine with colchicine or NSAID (not aspirin)
*site of inhibition of PGE2 production by NSAIDs
hypothalamus
characteristic of mild intox of aspirin
tinnitus
