NSAIDs

Question 1

common mechanisms of NSAIDs

Answer 1

inhibit COX, which blocks formation of prostaglandins, thromboxane A2

Question 2

function of PGI2

Answer 2

vasodilation, inhibits platelet aggregation

Question 3

function of TXA2

Answer 3

vasoconstriction, platelet aggregation

Question 4

function of PGI2 and PGE2

Answer 4

decrease gastric acid secretion; lower pain threshold

Question 5

function of PGE2 and PGF2

Answer 5

contract uterine smooth muscle

Question 6

major sites of COX1 expression (which could result in toxicity of NSAIDs)

Answer 6

platelets, kidneys, blood vessels, stomach

Question 7

when is COX2 expressed vs when COX1 is expressed?

Answer 7

COX2 expression is induced during inflammation; COX1 expression on nearly every cell

Question 8

how do NSAIDs produce analgesia?

Answer 8

by blocking production of prostaglandins, which lower pain threshold. effective against mild to moderate dull, aching pain; act synergistically with opiates

Question 9

how do NSAIDs produce anti-inflammatory effects?

Answer 9

reduce edema by bocking PGE2, PGI2; reduce pain; high concs of NSAIDs reduce neutrophil migration

Question 10

how are NSAIDs antipyretic?

Answer 10

PGE2 alters body temp set point, so it blocks production of PGE2

Question 11

clinical uses of NSAIDs

Answer 11

pain, primary dysmenorrhea, joint inflammation, fever

Question 12

why is GI distress, damage, bleeding a common side effect of NSAIDs?

Answer 12

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

Question 13

common renal side effects of NSAIDs

Answer 13

fluid retention (increased AHD activity), decreased sodium excretion, decrease GFR, interstitial nephritis

Question 14

common vascular side effects of NSAIDs

Answer 14

prolonged bleeding time and hypertension in sensitive patients.

Question 15

contraindications of NSAIDs

Answer 15

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)

Question 16

salicylate NSAIDs

Answer 16

aspirin, diflunisal

Question 17

acetic acid derivative NSAIDs

Answer 17

indomethacin, ketorolac

Question 18

proprionic acid derivative NSAIDs

Answer 18

ibuprofen, naproxen

Question 19

enolic acid derivative NSAIDs

Answer 19

meloxicam

Question 20

COX2 selective NSAID

Answer 20

celecoxib

Question 21

mechanism of action of salicylates (aspirin)

Answer 21

binds to COX irreversibly!; alters ratio of PGI2:TXA2 in the vasculature (decreases TX over time)

Question 22

describe what happens to TXA2 and PGI2 in an endothelial cell after a dose of aspirin

Answer 22

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.

Question 23

to reduce the chance of a 2nd MI, a px must..

Answer 23

take a low dose aspirin once every day

Question 24

PCKNs of aspirin/salicylates

Answer 24

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

Question 25

symptoms of mild intoxication of aspirin (and how many grams?)

Answer 25

6-7 g: tinnitus, vomiting, vertigo, hyperventilation (resp alkalosis)

Question 26

symptoms/dose of moderate aspirin toxicity

Answer 26

8-10 g; increased metabolic rate, fever, metabolic acidosis

Question 27

symptoms/dose of severe aspirin toxicity

Answer 27

20-50 g: respiratory depression, higher free conc of drug, acid/base probs, dehydration, loss of electrolytes, coma, renal and resp failure

Question 28

treatment for salicylate intoxication

Answer 28

cool, rehydrate, correct electrolyte imbalance, prevent further absorption (emesis), alkalinize the urine to increase excretion (bicarb, or sodium citrate), hemodialysis, diazepam for convulsions

Question 29

contraindications of aspirin

Answer 29

px w/ renal disease, bleeding disorders, hypersensitivity, gout, young child after viral infection (reyes syndrome), use w/ caution during 3rd trimester

Question 30

properties of ibuprofen (proprionic acid derivative) at low doses vs high doses

Answer 30

low dose: more effective analgesic high dose: anti-inflammatory activity as effective as aspirin

Question 31

half life of naproxen (proprionic acid deriv)?; potency?

Answer 31

long T1/2: 13 hr intermediate potency

Question 32

most potent NSAID

Answer 32

indomethacin (acetic acid deriv)

Question 33

clinical uses of indomethacin

Answer 33

acute gout, spondylitis, osteoarthritis, ductus arteriosus

Question 34

NSAID that can be given IM or IV (orally and IV)/ clinical use?

Answer 34

ketorolac; short-term pain management

Question 35

half life of meloxicam/ what's its more selective for / clinical uses

Answer 35

20 hr COX2 osteoarthritis, RA

Question 36

why do selective COX2 inhibitors (celecoxib) have a health advisory?

Answer 36

they also have some selective inhibitor activity against PGI2 synthase; increased incidence of CV events

Question 37

studies show that non-aspirin NSAID use..

Answer 37

increases the incidence of arial fib and increases recurrent MI; even short-term use is not advised in px with known CV disease

Question 38

what is gout caused by? what triggers the inflammation?

Answer 38

metabolic disorder characterized by hyperuricemia and deposition of monosodium urate in joints; inflammation triggered by action of granulocytes trying to remove the urate crystals

Question 39

drugs for acute treatment of gout

Answer 39

colchicine, indomethacin colchicine-highly toxic but good for acute attacks; nausea, vomiting, diarrhea

Question 40

drugs for prevention of gout

Answer 40

probenecid (urate diuretic) inhibits renal tubular reabsorption of urate allopurinol (XO inhibitor) blocks urate synthesis by suicide inhibition of XO

Question 41

side effect of uricosuric agents and XO inhibitors

Answer 41

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)

Question 42

*site of inhibition of PGE2 production by NSAIDs

Answer 42

hypothalamus

Question 43

characteristic of mild intox of aspirin

Answer 43

tinnitus