Mkgrady8 Gpmdc 3 Nsaids I

Front 1

what are the traditional NSAIDS and non narcotic analgesics

Back 1

aspirin (aka acetyl salicyclic acid) and acetaminophen

Front 2

what are the cox-2 selective agents

Back 2

celecoxib (celebrex)

Front 3

general mechanism of NSAIDS

Back 3

they act by inhibiting the cyclooxygenase (COX) enzyme; inhibition of the COX enzyme blocks the production of the prostaglandin's which mediate the pathogenesis of inflammation and fever; so their actions are= ANTI INFLAMMATORY, ANALGESIC (this is why they're also called non-narcotic analgesics), AND ANTIPYRETIC

Front 4

what are the roles of prostaglandins in inflammation

Back 4

vasodilation, vascular permeability, sensitizes nerve receptors to other inflammatory mediators, fever

Front 5

so where does the inhibition of cyclooxygenase (COX) fit in with the inflammatory process

Back 5

arachidonic acid is first acted on by COX on it's way to making prostaglandins, thromboxanes (prothrombotic compound), or prostacyclines (antithrombotic compounds); have to be a little carful blocking COX through because then arachidonic acid can be pushed into its alternate route of leukotrienes (can cause bronchospams)

Front 6

what effect do prostaglandins have on the stomach

Back 6

increase mucous secretion, increase bicarb secretion, inhibit gastric secretion

Front 7

what effect does thromboxane have on the blood

Back 7

inducer of platelet aggregation

Front 8

what effect do prostaglandins have on the kidney

Back 8

modulates the production of renin, and of renal blood flow (causes vasodilation)

Front 9

what effect do prostaglandins have on inflammation

Back 9

vasodilation and increased vascular permeability; cause pain; cause the hypothalamus to increase body temp (fever)

Front 10

when aspirin interacts with COX where does it act

Back 10

on serine 530; it acetylates it; THIS IS UNIQUE AMONG TH NSAIDS BECAUSE BY ACETYLATING THE ACTIVE SITE IT IRREVERSIBLY INACTIVATED THE ENZYME; this means that the platelets are no longer able to make any of the arachidonic break down products (except the leukotrienes) until their death and therefore clearance of the drug (will have blood thinning effect for many days)

Front 11

so what is the difference between this COX-1 and COX-2

Back 11

we didn't know that there were these 2 isoforms; COX-2 is only expressed in the BRAIN and parts of the KIDNEY, AND ENDOTHELIUM (AND OVARY); otherwise it is very similar to COX-1 and inhibited by the same things (but could we make one that is specific to COX-2? and why would that be helpful?)

Front 12

stress in the kidney leads to what

Back 12

dehydration leads to an increase in COX-2 expression which produces prostaglandins that play an important role in preserving renal function; this example is just to show that COX-2 does have some specific functions different from that of COX-1

Front 13

COX-2 in the brain

Back 13

in the hypothalamus the production of prostaglandins by COX-2 is what is responsible for resetting the body's thermostat during fever

Front 14

overall responsibilities of COX-1 and COX-2

Back 14

COX-1 is responsible for the homeostatic functions of prostaglandins (ex. stomach mucin) while COX-2 is responsible for the inflammatory response as well as some homeostatic functions

Front 15

side effects of our standard NSAIDS

Back 15

the blocking of the homeostatic functions of COX-1 as well as the inflammatory of COX-2; gastric ulcers, blockade of platelet agg, inhibition of uterine motility, inhibition of prostaglandin mediated renin production, inhibition of fever, inhibition of pain, inhibition of inflammation

Front 16

examples of some COX (in general) inhibitors (NSAIDS)

Back 16

aspirin, indomethacin, ibuprofen, acetaminophen, diclofenac, naproxen

Front 17

the COX-2 inhibitor that we will study

Back 17

CELECOXIB aka celebrex (way more specific for COX-2 than for COX-1)

Front 18

what is the problem with Vioxx and Bextra

Back 18

they are also COX-2 inhibitors and so they inhibited the formation of PGI2 (an antithrombotic agent) so basically they increased the risk of thrombosis (people were having heart attacks) and they were taken off the market; why doesn't celebrex do this? it probably does do this but they stopped the studies (protect their product) (don't give it to a pt that even has a slight risk of MI); also it has slightly less specificity for COX-2 than the others (so maybe some COX-1 thrown in is good)

Front 19

a 62 y/o women has recently become a pt of your and you havediagnosed her as having rheumatoid arthritis (RA). This pt also has a history of coronary heartdisease. In discussing treatment optionsfor her RA, in addition to prescribing a DMARD (disease modifyinganti-rheumatic drug), you express a hesitation in prescribing celecoxib(celelbrex). In your explanation to heryou point out that this drug is a COX-2 selective inhibitor and like anotherCOX-2 selective inhibitor (Rofecoxib, Vioxx) that was taken off the market,over time it may inhibit the production of WHICH EICOSANOID that is thenassociated with an increase in the risk of a cardiovascular event (e.g.myocardial infarction)?A. thromboxane A2(TXA2)B. prostaglandin E1(PGE1)C. prostacyclin I2(PGI2)D. Prostaglandin F2(PGF2)E. Leukotriene (LTB4)

Back 19

C. prostacyclin I2 (PGI2)