Eicosanoids and NSAIDs

Question 1

What are eicosanoids? (molecule type, examples)

Answer 1

class of lipids include prostaglandins, throboxanes, leukotrienes

Question 2

What is the COX2 seletive NSAID I should know? Benefits/side effects?

Answer 2

celecoxib. theoretically would decrease GI discomfort. sides: inhibit PG production in kidney: hypertension and edema: increased MIs. give at low dose for short periods.

Question 3

Misoprostol: uses? class/type?

Answer 3

PGE1 analogue/PGE agonist prevents NSAID induced gastric ulcers. also, therapeutic abortion.

Question 4

What do NSAIDS treat? What are the two types of NSAIDS? MoA?

Answer 4

treat inflammation ,fever, and pain. traditional NSAIDS block all COX enzymes. Newer enzymes are somewhat selective for COX2. All except aspirin are competitive inhibitors. Inhibit PG and TX synthesis.

Question 5

Where do the cardiovascular benefits of aspirin come from?

Answer 5

aspirin is an irreversible non-selective COX inhibitor. COX in platelets is especially sensitive, since platelets can’t regenerate COX.

Question 6

What is the most common precursor of eicosanoids? (in humans) Why are eicosanoids hard to study?

Answer 6

arachidonic acid they are hard to study because the reaction to eicosanoids varies widely from tissue to tissue and from species to species.

Question 7

What are the leukotriene inhibitor classes and uses?

Answer 7

reduce bronchoconstriction of asthma and allergens Classes are 5-lipoxygenase inhibitors to prevent LT synthesis and LT receptor inhibitors

Question 8

What are the four traditional NSAID I need to know? Any exceptions in usage/MoA>

Answer 8

aspirin (irreversible inhibitor, not competitive), ibuprofen, naproxen (alleve), and acetominophen (does not have anti-inflammatory benefits).

Question 9

What kinds of effects to eicosanoids usually have?

Answer 9

local effects: many enzymes degrade them, and active eicosanoids usually not found in systemic circulation. and they work in conjunction with other processes: sensitizing or antagonizing agents.

Question 10

Describe, very basically, eicosanoid biosynthesis.

Answer 10

derived from arachodonic acid, which is usually trapped in the plasma membrane. synthesis depends on the release of arachodonic acid from the plasma membrane, usually related to stimuli that lead to an increase in intracellular calcium. Increased calcium causes the translocation of cytosolic PLA2 to the plasma membrane, where PLA2 can free arachidonic acid. This arachidonic acid is metabolized to various eicosanoids.

Question 11

What is lipocortin?

Answer 11

a protein that inhibits PLA2 and thus inhibits the synthesis of eicosanoids (no arachodonic acid release from the plasma membrane). Incudeable by glucocordicoids and partially explains their anti-inflammatory action.

Question 12

What are COX enzymes (function, pharm significance)

Answer 12

enzymes that make prostaglandins and thromboxanes from free arachidonic acid. This is the enzyme that is inhibited by NSAIDs.

Question 13

What are the 2 forms of COX?

Answer 13

COX1: constitutively expressed. helps with cytoprotetction and gastric endothelium protection. COX2: induced by stimuli and palys a role in inflammation and cancer.

Question 14

How are leukotrienes made from free arachidonic acid?

Answer 14

lipoxygenases form HPETEs from arachidonic acid. HPETEs rapidly metabolized to active leukotrienes.

Question 15

Eicosanoid receptors: types? effects?

Answer 15

all are membmrane boud G protein coupled receptors. diversity of responses: LARGE number of receptors and a diverse number of signaling cascades.

Question 16

What are the effects of eicosanoids on platelets? Which eicosanoids are important, source, and what are their effects?

Answer 16

TXA2. contributes to increased platelet aggregation and blood clotting at injury sites, as well as in pathologies like CVA and MI. PGI2 inhibits platelet aggregation and disaggregates preformed clumps. PGI2 synthesized by endothelial cells to counteract effects of TXA2.

Question 17

What is a use for PGF agonists?

Answer 17

treat glaucoma

Question 18

What are the effects of eicosanoids on vascular tone? Which eiconosoids, source, effects, triggers

Answer 18

only local effects. PGI2 made by COX is released by endothelial cells. relaxes blood vessels. sheer stress triggers the release of PGI2.

Question 19

What eicosanoids play a role in the lungs? triggers?

Answer 19

leukotrienes. generally released in response to inflammatory agents. cause bronchoconstriction and leukocyte invasion.

Question 20

What is the role of eicosanoids in the inflammatory response?

Answer 20

In general, prostaglandins and leukotrienes are potent mediators of the immune response and acute inflammatory response. increase local blood flow, increase vascular permeability, and promote leukocyte infiltration.

Question 21

What is the role of eicosanoids in the kidneys, and what is the significance of this?

Answer 21

long term use of all COX inhibitors limited by effects on the kidney: hypertension, edema, CHF. In part because eicosanoids play a role in renal blood flow and salt excretion.

Question 22

Role of eicosanoids in the uterus.

Answer 22

nonpregnant: PGFs contract and PGEs relax. Pregnant uterus: muscle contraction.

Question 23

What are the effects of eicosanoids on the stomac?

Answer 23

PGs inhibit gastric acid secretion

Question 24

Effects of eicosanoids on the nervous system.

Answer 24

Pain- PGE2 and PGI2 and LTB4 increase sensitivity to nociceptors. and, fever mediated by PGE2 in the hypothalamus.

Question 25

What are the effects of eicosanoids on the eye?

Answer 25

PGF2 increases outflow of aqueous humor: decr. intraoculuar pressure.