Arachadonic acid metabolites (acute inflammation)

Question 1

Arachadonic Acid

Answer 1

is present in esterified form in membrane phospholipids

Eicosonoids are AA metabolites

Question 2

Eicosanoids

Answer 2

bind G protein coupled receptors on many cell types and can be involved in nearly every step of inflammation

Question 3

How are ARACH AC freed from membrane phospholipids?

Answer 3

Phospholipase A2

Corticosteroids inhibit Phospholipase’s action

Question 4

Bifurcation of Arch Ac pathway

Answer 4

cyclooxygenases make prostaglandins

lipoxygenases make various “HPETEs”…Leukotrienes and Lipoxins

Question 5

Cox type 1

Answer 5

constitutively expressed in most tissues and is central to a metabolic pathway protecting the gastric lining from the acid it produces

Thus chronic NSAID use has loss of stomach lining as a side effect because these are non specific cox1 and cox2 inhibitors

Question 6

Cox type 2

Answer 6

minimally expressed under normal conditions

Induced by inflammation!!

Question 7

Downstream of COX, vasc endo cells have the enzyme _______with converts PGH2 into _____ aka _______.

Which does what?

Answer 7

prostacyclin synthetase

PGH2-> PGI2

PGI2 “prostacyclin” dilates blood vessels and inhibits platelet aggregation

Question 8

Prostacyclin has the opposite funciton of ____?

Answer 8

Thromboxane A2

Question 9

Platelets express enzyme called ________?

This enzyme converts PGH2-> ?

which does what?

Answer 9

thromboxane synthetase

PGH2-> THROMBOXANE A2

constricts blood vessels and promotes platelet aggregation

Question 10

Mast cells make which prostaglandin? and what does it do?

Answer 10

PGD2

• vasodilation
• incr vasc perm
• chemoattractant for neutrophils

Question 11

PGE2

Answer 11

vasodilation

incre vasc perm

Question 12

PGF2

Answer 12

CONTRACTION of uterus, bronchioles, arteriole smooth muscle

Question 13

5 Lipoxygenase converts arachadonic acid to _____

Answer 13

5HPETE (mainly in neutrophils)
5HETE is chemoattr for more neutrophils
5HPETE is the precursor for all the leukotrienes

Question 14

LTB4

Answer 14

potent chemoattractant for neutrophils

activator of neutrophils

Question 15

LTC4, LTD4, LTE4

*acting on venules primarily

Answer 15

intense vasoconstriction  (opposite of H...vasodilation)
intense bronchoconstriction  (more than H)
intensely increased vascular permeability (more than H)

Question 16

Lipoxins A4 & B4

5HPETE produced by 5-lipoxygenase can be converted to these lipoxins. They are anti-inflammatory, inhibit neutrophil chemotaxis, and inhibit adhesion to endothelium.

Answer 16

Leukocytes (neutrophils) produce intermediates in lipoxin synthesis, and these are converted to lipoxins by platelets interacting with the leukocytes.

Question 17

ASthma drugs?

Answer 17

lipoxygenase inhibitors

leukotriene receptor blockers

Question 18

Bradykinin (no an eicosanoid btw)

short lived peptide generated from plasma kininogens by kallikreins

Answer 18

• pain
• vasodilation
• increased vasc perm

-a mediator of anaphylaxis

Question 19

PAF: Platelet Activating Factor

low dose?
high dose?

Answer 19

lose dose: vasodilation and incre vasc perm

high dose: VASOCONSTRICTION AND BRONCHOCONSTRICTION