Block 2: Inflammation and Eicosanoids

Question 0

Histamine: source, physiological response, mechanism

Answer 0

source: mast cells and basophils
response: vasodilation, increased vascular permeability, pain
mechanism: activation of GPCRs

Question 1

Bradykinin: what is it, source, physiological response, mechanism

Answer 1

type: vasoactive peptide
source: endothelial cells
response: vasodilation, increased microvessel permeability, pain
mechanism: activation of GPCRs

Question 2

Elevated CRP is associated with what?

Answer 2

increased risk of diabetes, hypertension, and cardiovascular disease

Question 3

Cytokines: two pro-inflammatory examples, how they cause fever

Answer 3

IL-1, TNF-alpha
Increased expression of cyclooxygenase in hypothalamus -> increased formation of PGE2 which acts via cAMP to reset temperature set-point in hypothalamus -> increase body temp.

Question 5

Prostaglandin: what is it, physiological response, mechanism

Answer 5

pro-inflammatory lipid mediator

response: vasodilation/vasoconstriction, pain, fever, platelet aggregation
mechanism: activation of specific GPCRs

Question 5

Glucocorticoids: what they are, source, physiological response, mechanism

Answer 5

anti-inflammatory lipid mediators that inhibit arachidonic acid release

source: adrenal cortex
response: decrease expression of COX-2 and inhibits phospholipase-A2 (enzyme that cleaves phospholipid and releases arachidonic acid)
mechanism: activation of nuclear receptors

Question 6

Leukotrienes: what is it, source, physiological response, mechanism

Answer 6

pro-inflammatory lipid mediator

response: increased vascular permeability, chemoattractant for neutrophils, bronchoconstriction
mechanism: activation of GPCRs

Question 7

NSAIDs: mechanism

Answer 7

inhibition of cyclooxygenase, reduces production of inflammatory prostanoids

Question 8

zafirlukast and zileuton: what each of them are, theapeutic use

Answer 8

zafirlukasat: competitve antagonist of leukotriene receptors
zileuton: inhibits 5-lipoxygenase and thus the synthesis of leukotrienes
use: prophylaxis and chronic treatment of asthma

Question 9

TNF inhibitors (2)

Answer 9

etanercept, infliximab

Question 10

etanercept and infliximab

Answer 10

TNF inhibitors

etanercept: receptor analog
infliximab: monoclonal antibody

Question 11

precursor of eicosanoids

Answer 11

arachidonic acid

Question 12

what enzyme synthesizes leukotrienes and from what precursor?

Answer 12

5-lipoxygenase from arachidonic acid

Question 14

prophylaxis and chronic treatment of asthma (2)

Answer 14

zileuton and zafirlukast

Question 15

Complement system: source, physiological response, mechanism

Answer 15

source: synthesized by liver, circulate in blood
physiological response: chemotaxis, release of mediators from neutrophils, increase vascular permeability
mechanism: complement complexes cause osmotic lysis, activation of GPCRs

Question 16

Cytokines: physiological response, mechanism

Answer 16

physiological response:
TNF-alpha: fever, sepsis
IL-1: fever, fibroblast and lymphocyte proliferation
mechanism:
1. increase cyclooxygenase and lipoxygenase
2. increase adhesion molecule expression
3. induce collagenase (fibrosis)

Question 17

function of phospholipase A2

Answer 17

hydrolyzes phospholipids to release arachidonic acid

Question 18

function of cyclooxygenase

Answer 18

converts free arachidonic acid to PGH2 which is transformed enzymatically to prostacyclin, thromboxane, PGE2, PGF2

Question 19

difference between COX-1 and COX-2

Answer 19

COX-1 is constitutive and expresed in all tissues

COX-2 is inducible and is more commonly seen in inflammation

Question 20

function of 5-lipoxygenase

Answer 20

synthesize leukotrienes from arachidonic acid

Question 21

types of drugs that inhibit phospholipase A2

Answer 21

glucocorticoids

Question 22

type of drug that inhibit COX-1 and COX-2

Answer 22

NSAIDs

Question 23

type of drug that decrease expression only of COX-2

Answer 23

glucocorticoids

Question 24

inhibitors of lipoxygenase

Answer 24

zileuton and zafirlukast

Question 25

physiological response of leukotrienes

Answer 25

bronchoconstriction, increase vascular permeability, chemotaxis

Question 26

inhibits 5-lipoxygenase

Answer 26

zileuton

Question 27

leukotriene receptor antagonist

Answer 27

zafirlukast

Question 28

Eicosanoids related to pain in periphery

Answer 28

PGE2 and PGI2

Question 29

what eicosanoid is important in fever?

Answer 29

PGE2

Question 30

what second messager molecule is important in fever?

Answer 30

cAMP

Question 31

what eicosanoid is responsible for platelet aggregation and what is the mechanism? include appropriate receptor

Answer 31

thromboxane mechanism: activation of phospholipase A2 --> release of arachidonic acid --> converted to thromboxane by COX-1 --> stimulates TP receptors that couple to increase in calcium

Question 32

does thromboxane cause vasocontstriction or vasodilation?

Answer 32

vasoconstriction

Question 33

what eicosanoid is responsible for inhibiting platelet aggregation and what is the mechanism? include appropriate receptor

Answer 33

prostacyclin (PGI2) mechanism: activation of phospholipase A2 --> release of arachidonic acid --> converted to prostacycling by COX-1 and COX-2 --> stimulates IP receptor that couples to cAMP

Question 34

does prostacyclin cause vasoconstriction or vasodilation?

Answer 34

vasodilation

Question 35

what is the cellular source of prostacyclin?

Answer 35

endothelial cells

Question 36

what prostaglandins cause vasodilation of cardiovascular/vascular smooth muscle?

Answer 36

PGE2, PGI2

Question 37

which prostaglandin is a potent vasoconstrictor?

Answer 37

thromboxane

Question 38

circulating vasoconstrictor autocoid

Answer 38

angiotensin II

Question 39

what prostaglandin maintains patency of ducrus arteriosus?

Answer 39

PGE2

Question 40

what prostaglandins increase renal blood flow via vasodilation?

Answer 40

PGE2 and PGI2

Question 41

which COX enzye is important in GI and how?

Answer 41

COX-1, synthesize cytoprotective prostaglandins that inhibit gastric acid secretion, stimulates release of mucus, increase gastric mucosal blood flow

Question 42

why are therapeutic uses of prostaglandins limited?

Answer 42

adverse effects and short half-life

Question 43

dinoprostone: analog of what, therapeutic uses, second messengers, adverse effects

Answer 43

PGE2 analog uses: cervical ripening and termination of early pregnancy second messengers: calcium, cAMP adverse effects: GI-related, fever

Question 44

what is the only PGE2 analog?

Answer 44

dinoprostone

Question 45

misoprostone: analog of what, therapeutic use, second messenger, adverse effects

Answer 45

PGE1 analog use: prevention of ulcers caused by NSAIDs second messenger: cAMP adverse effects: contraindicated in pregnancy

Question 46

analogs of PGE1

Answer 46

misoprostol, alprostadil

Question 47

alprostadil: analog of what, therapeutic uses, second messenger

Answer 47

PGE1 analog uses: impotence, maintenance of patent ductus arteriosus second messenger: cAMP

Question 48

epoprostenol: analog of what, therapeutic use, mechanism (include appropriate receptor and second messenger)

Answer 48

PGI2 analog use: primary pulmonary hypertension mechanism: acts at PGI2 or IP receptor to cause a cAMP-mediated dilation of pulmonary artery vascular smooth muscle