Eicosanoids, Thermoregulation, Inflammation, and Coagulation

Question 1

What are eicosanoids?

Answer 1

Signaling molecules created from the metabolism of arachidonic acid (metabolites)- responsible for pain, inflammation, fever, and diseases associated with inflammation

Question 2

What is the role of phospholipids A2 role in Arachidonic acid metabolism?

Answer 2

PLA2 acts on the phospholipid of cell membrane to release arachidonic acid

Question 3

What causes the cell phospholipids to be converted into arachidonic acid?

Answer 3

Physical, chemical, inflammatory, and nitrogen if stimuli with the enzyme phospholipase A2

Question 4

What are the pathways of metabolism of arachidonic acid?

Answer 4

1. Cyclooxygenase (COX)
2. Lipooxygenase (LOX)
3. Cytochrome P450 (CYP)

Question 5

What are the types of eicosanoids derived from the COX pathway?

Answer 5

Prostacyclins, prostaglandins, thromboxanes

Question 6

How can PGE1 analog be used in patient with patent ductus arteriosus?

Answer 6

After birth PGE1/PGE2 decreases to close patent ductus arteriosus but PGE1 analogs can keep it open in the cases of certain congenital heart diseases until the patient can get surgery

Question 7

Describe the clinical uses of Topiglan:

Answer 7

-PGE1 analog
-MOA= vasodilation in corpus cavermosum
-indication= injectable for erectile dysfunction

Question 8

Describe the clinical uses of Misoprostol:

Answer 8

-PGE1 analog
-MOA=cytoprotection, increases mucin and bicarbonate production
-indication= prevention of peptic ulcers for patients that take high doses of NSAIDs or vaginal inserts can be given to pregnant individuals to induce labor

Question 9

Describe the clinical uses of Dinoprostone:

Answer 9

-PGE2 analog
-MOA= low concentrations induced contraction of pregnant uterus
-Indication= labor

Question 10

Describe the clinical uses of Lantanoprost:

Answer 10

-PGF2a analog
-MOA= increases ureoscleral outflow
-indication= topical treatment of glaucoma

Question 11

Describe the clinical uses of Epoprostenol:

Answer 11

-prostacyclin PGI2
-MOA= vasodilator or inhibitor of platelet aggregation
-indication= pulmonary hypertension and can be used for patients on dialysis to avoid clotting in machine

Question 12

What is the role of naturally occurring eicosanoids?

Answer 12

Pain, thermoregulation, coagulation, inflammation

Question 13

What is the role of eicosanoids in pain?

Answer 13

Nociceptors (specialized neurons that initiate the sensation of pain), tissues, an inflammatory cells produce prostaglandins (eicosanoids) that affect pain transmission- pain perception is induced by eicosanoids by sensitizing nociceptors

Question 14

Define: allodynia

Answer 14

Perception of pain from normal stimulus

Question 15

Define: hyperalgesia-sensitization

Answer 15

Exaggerate response to pain stimulus

Question 16

Describe PGE2 responsibility in peripheral sensitization hyperalgesia:

Answer 16

Increased COX-2 expression increases PGE2 sensitization -> increases terminal membrane excitability-> inflammatory hyperalgesia

Question 17

Describe PGE2 responsibility in central centralization hyperalgesia:

Answer 17

Enhanced spinal dorsal horn neuron excitability that augments pain intensity widens the perception area results in pain from innocuous stimuli

Question 18

What is the mechanism of analgesic action of Aspirin and NSAIDs?

Answer 18

COX inhibitors

Question 19

What is the role of eicosanoids in thermoregulation?

Answer 19

Fever results when set point of anterior hypothalamic regulatory center is elevated by PGE2 synthesis that is stimulated by pyrogens (ex cytokines from white blood cells)

Question 20

Describe the antipyretic (anti-fever) effects of COX inhibitors?

Answer 20

Fever plays a critical role in innate immunity and drive heat sensitive activities such as recruiting Tcells and neutrophils but COX inhibitors impede PGE2 synthesis and release

Question 21

Describe the role of eicosanoids in blood coagulation?

Answer 21

-PGI2 prevents platelet aggregation when vascular endothelial is intact
-TXA2 encourages platelet aggregation when vascular endothelial is damage
together they control coagulation

Question 22

How do COX2 inhibitors effect blood coagulation?

Answer 22

Increase TXA2 which increases coagulation which increases CVD risk

Question 23

Describe the MOA of aspirins anti-coagulation effects:

Answer 23

-Inhibits COX activity thus reducing TXA2 (by platelets) and reduces PGI2 (by endothelial cells)
-endothelial cells= nucleus= new COX, but platelets= no nucleus= no COX, so PGI2 synthesis is greater than TXA2
-net results of decreased coagulation

Question 24

What are the risks of taking aspirin long-term?

Answer 24

Bleeding risk

Question 25

Describe the MOA of taking aspirin and NSAIDs concurrently:

Answer 25

-aspirin binds irreversibly to platelets through acetylation
-NSAIDs bind reversible with H bonds and can inhibit aspirins anti-platelet effects
take aspirin 30 mins before NSAIDs, then wait at least 8 hours before taking aspirin again