Hormonal/Lipid Mediators (Cardio)

Question 1

NSAID potency is paralled by:

Answer 1

Potency of prostaglandin inhibition

Question 2

Arachidonic acid is a precursor for what?

Answer 2

biological active lipids

Question 3

PUFA stands for? Comes from?

Answer 3

Poly-unsaturated fatty acids from our diet

Question 4

How and Why would you want to store arachidonic acid?

Answer 4

Stored esterified in membrane phospholipids. Cause it’s POTENT once activated!

Question 5

How do you RELEASE THE (arachidonic acid) KRAKKEN? (from the membrane?)

Answer 5

increase intracellular calcium

Question 6

2 ways to metabolize arachidonic acid:

Answer 6

1. COX1 (constitutive)- physiological PGs

2. COX2 (inducible) - gene induced by inflammatories like IL-1/TNF

Question 7

COX-1 and COX-2 are expressed in which cells

Answer 7

ALL THE CELLS.

Question 8

Features of Cyclic endoperoxides? what happens to them?

Answer 8

Highly unstable and converted to PGE, PGF, PGD

Question 9

T/F Prostaglandins survive in the blood stream.

Answer 9

False. degraded by endothelial cells

Question 10

PGE2 does what 5 things?

Answer 10

1. Relaxes smooth muscle
2. vasodilator
3. hyperalgesic
4. pyrogenic
5. angiogenic

Question 11

PGD2 and PGF2-alpha do what?

Answer 11

both bronchoconstrict

Question 12

Main action of NSAIDs?

Answer 12

block cyclooxygenase

Question 13

NSAID adverse effect?

Answer 13

gastric irritation/ulceration

Question 14

Do NSAIDS influence cellular inflammation?

Answer 14

Nope. Mostly vascular.

Question 15

Explain the synergy between PGE2 and BK

Answer 15

BK alone increases paina smidge, PGE alone only makes it red. Together they form a dynamic duo and BRING THE PAIN.

Question 16

If PGE2 only acts locally, how does it get to the hypothalamus to cause fever

Answer 16

IL-1 travels from infection to hypothalamus, induces COX2 to produce PGE2 to turn the heat up.

Question 17

PGE2 isn’t all bad, tell me 4 reasons why?

Answer 17

1. Promotes blood flow
2. promotes angiogenesis
3. increases music secretion
4. reduces gastric acid secretion

Question 18

Is Thromboxane A2 a prostaglandin?

Answer 18

Nope. Missing the pentacyclin ring

Question 19

What’s the half life of Prostacyclin?

Answer 19

3 minutes

Question 20

Prostacyclin is our protector against coronary artery disease. 2 reasons why?

Answer 20

1. reduce platelet activation

2. vasodilator

Question 21

What is the half-life of Thromboxane A2?

Answer 21

30 seconds

Question 22

What makes Thromboxane A2?

Answer 22

Platelets

Question 23

Thromboxane A2 is prostacyclin’s evil twin brother. Two reasons why?

Answer 23

1. increases platelet activation

2. vasoconstrictor

Question 24

Why is Aspirin so special?

Answer 24

1. Promotes prostacyclin

2. Acetylation of COX

Question 25

What does Aspirin do to platelets?

Answer 25

irreversibly binds to them

Question 26

Platelet life span is how long?

Answer 26

8 days

Question 27

PGI2 aka....

Answer 27

Prostacyclin

Question 28

What are Aspirin triggered lipoxins?

Answer 28

Lipoxins involved in inflammation resolution.

Question 29

What happens if you convert linolenic acid to Eicosapentaenoic (EPA) instead of arachidonic acid?

Answer 29

Increase PGI3 instead of TxA3

Question 30

What does Increased PGI3/TxA3 ratio mean?

Answer 30

lower risk of heart disease

Question 31

5 Lipoxygenase does what? how is it activated? where is it found?

Answer 31

Inflames shit up. Activated by increased calcium via infection, allergic etc. ONLY found in inflammatory cells.

Question 32

We like to target 5 lipoxygenase with drugs. Why?

Answer 32

It's ONLY found in inflammatory cells so we can minimize side effects

Question 33

Leukotriene B4 does shit to smooth muscle, so how does it cause inflammation?

Answer 33

attracts leukocytes

Question 34

What does montelukast do?

Answer 34

blocks CysLT1R (hay fever and asthma)

Question 35

Why is a local mediator only act locally?

Answer 35

Rapidly metabolized or 'diluted'

Question 36

6 reasons why is the Mast Cell so Mighty:

Answer 36

``` -Antigen via IgE – Complement fragments C3a/C5a – Neuropeptides – Cytokines and chemokines – Bacterial components – Physical trauma ```

Question 37

Histamine interact with what kind of receptors?

Answer 37

G-Protein Coupled Receptors (H1-4)

Question 38

What's Histamine's Triple Response?

Answer 38

1. Reddening: vasodilation at initiating site 2. Swelling: increase vascular permeability 3. Flare: response through sensory fibres

Question 39

What is Pruritus?

Answer 39

Itching

Question 40

Antihistamines target which receptor?

Answer 40

H1

Question 41

Name 2 sedative antihistamines

Answer 41

chlorpheniramine | promethazine

Question 42

Name 2 non-sedative antihistamine drugs. Why were they withdrawn from market?

Answer 42

terfenadine | astemizole

Question 43

Name two newer non-sedative agents?

Answer 43

Cetirizine | Loratidine

Question 44

Name two H2 receptor antagonists. What do they treat?

Answer 44

Cimetidine Ranitidine Both treat peptic ulcers

Question 45

Generally: Bradykinin is and does what?

Answer 45

Local peptide mediator for pain and inflam

Question 46

Bradykinin degrades into Kininase I and II, Kininase II is also known as:

Answer 46

Angiotensin Converting Enzyme

Question 47

Neural action of Bradykinin?

Answer 47

stimulate sensory nerve endings: Pain

Question 48

Other actions of Bradykinin?

Answer 48

1. contract uterus, airways, gut | 2. epithelial secretion in airways, gut

Question 49

Vascular actions of bradykinin?

Answer 49

Dilate arterioles and venules | Increase vascular permeability

Question 50

What is icatibant?

Answer 50

Selective B2 receptor antagonist for Rx of hereditary angioedema (too much BK)

Question 51

When the endothelium was removed from a vessel, what does Acetylcholine act like?

Answer 51

Vasodilator

Question 52

When the endothelium was intact from a vessel, what does Acetylcholine act like?

Answer 52

vasoconstrictor

Question 53

EDRF stand for?

Answer 53

endothelium-derived relaxant factor (ie. NO)

Question 54

EDHF stands for? does what?

Answer 54

endothelium-derived hyper polarizing factor, relaxes vessels

Question 55

Name the 3 isoforms of NOS

Answer 55

– nNOS (nerves, epithelial cells) – iNOS (inducible- macrophages, smooth muscle) – eNOS (endothelial cells)

Question 56

What is an L-NAME?

Answer 56

Inhibits NOS

Question 57

3 things that NOS does?

Answer 57

1. inhibit platelet adhesion and aggregation 2. Neurotransmitter 3. Wasodilates in response to shear forces