Eicosanoids and NSAIDs

Question 1

corticosteroids

Answer 1

anti inflammatory

act by inducing phospholipase A2 inhibitory proteins (lipocortins) so that arachidonic acid isn’t released

Question 2

PGI2 (prostacyclin):

Answer 2

binds to IP receptors on platelets
-facilitates anti-platelet function (dis-aggregation)
made in endothelial cells downstream of COX-2
increase CAMP
vaso/bronchodilation (relaxes sm muscle)
increases renal perfusion
increases pain sensation

Question 3

PGE2

Answer 3

binds to EP3 receptor in hypothalamus, gut
made downstream of COX1
vaso/bronchodilation
critical for fever
increases pain sensation
decreases NE
increases gut smooth muscle contraction
GI protective (decreases gastric acid secreation, increases GI mucous)
decreases cAMP

Question 4

PGF2alpha

Answer 4

req’d for induction of labor

PLC mediated

Question 5

TXA2

Answer 5

thromboxane A2: platelet aggregation
made in platelets
dependent on COX-1
vaso/bronchoconstriction

Question 6

Leukotrienes

Answer 6

vasoconstrictors, inflammation, causes leaky venules –> edema, bronchoconstrictoin (asthma, COPD, allergy)

Question 7

LTB4:

Answer 7

neutrophil chemoattractant, cauases PMNs to stick, migrate from circulation to tissues

Question 8

misoprostol:

Answer 8

PGE2 mimetic, decreases GI bleed/SFX

Question 9

Zileuton:

Answer 9

oral inhibitor of 5-Lipoxygenase (inhibits LTB4,C4,D4, E4 formation)

Question 10

acetaminophen

Answer 10

aka paracetamol, Tylenol
antipyretic, antianalgesic, not good for inflammation
weak inhibitor of Cox1,2; mechanism of action unknown
little to no GI bleeding
absorbed from GI tract, excreted in urine
hepatic toxicity

Question 11

aspirin

Answer 11

irreversible COX inhibitor
anti-inflammation, anti-analgesic, anti-pyretic in high doses (high enough to cause GI bleed)
low doses: platelet funciton inhibition
- decreased renal blood flow –> renal toxicity
-Reye’s syndrome in children

Question 12

Celecoxib (celebrex)

Answer 12

cox-2 selective inhibitor

Question 13

Rofecoxib (Vioxx)

Answer 13

cox-2 selective inhibitor

Question 14

Ibuprofen

Answer 14

aka Motrin, Advil, Naproxen
nonselective, competitive Cox inhib.
treats arthritis, fever, patent ductus arteriosus, etc

Question 15

Indomethacin

Answer 15

nonselective COX inhib
suppresses premature labor, treats patent ductus arteriosus
-frequent CNS SFX, not frequently used

Question 16

Ketonolac (Toradol):

Answer 16

NSAID, given IM or IV post surgery for analgesic

• no tolerance, respiratory depression, or withdrawal
• inhibit platelet aggregation
• oral only for a limited time (5d) after this, GI and renal toxicity