Local and Hormonal Mediators

Question 1

Where is histamine released from?

Answer 1

Granules stored in mast cells - mast cells located in places where body is in contact with the environment

Question 2

How are mast cells activated?

Answer 2

antigen activating IgE, complement cascade (C3a, C5a), neuropeptides, cytokines, chemokines, bacterial components, physical trauma

Question 3

What are histamine receptors?

Answer 3

H1-4 - GPCRs

Question 4

What are the three responses caused by histamine?

Answer 4

reddening (vasodilation), wheal (vascular permeability), flare (spreading through sensory fibres)

Question 5

What is the action of antihistamines?

Answer 5

H1 blockers

Question 6

When are antihistamines used?

Answer 6

In allergic symptoms, adjunct therapy to adrenaline for cardiovascular integrity, and for motion sickness because of actions in the CNS

Question 7

What is chlorpheniramine?

Answer 7

A competitive, reversible H1 receptor antagonist that is sedative

Question 8

What is promethazine?

Answer 8

A competitive, reversible H1 receptor antagonist that is sedative

Question 9

What is terfenadine?

Answer 9

A competitive, reversible H1 receptor antagonist that is non-sedative but may cause sudden ventricular arrhythmia

Question 10

What is astemizole?

Answer 10

A competitive, reversible H1 receptor antagonist that is non-sedative but may cause sudden ventricular arrhythmia

Question 11

What is cetirizine?

Answer 11

A competitive, reverislbe H! receptor antagonist that is non-sedative with fewer risks of unwanted cardiac effects

Question 12

What is loratidine?

Answer 12

A competitive, reversible H1 receptor antagonist that is non-sedative with fewer risks of unwanted cardiac effects

Question 13

What is the action of H2 receptor antagonists?

Answer 13

Regulate stomach acid secretion - originally used to treat peptic ulcers before the discovery of the bacteria causing them

Question 14

How is bradykinin synthesised?

Answer 14

Prekallikrein (an inactive plasma protein) is activated to kallikrein by cleavage by factor XII (hageman factor). Kalikrein then cleaves kininogen in to bradykinin

Question 15

What size is bradykinin?

Answer 15

9 amino acids

Question 16

How is bradykinin degraded?

Answer 16

Kinase II (angiotensin converting enzyme) cleaves off the last two enzymes of bradykinin

Question 17

What are the actions of bradykinin?

Answer 17

Vasodilator, increases vascular permeability, pain, contract uterus, airways, gut, epithelial secretion in airways and gut

Question 18

What are the bradykinin receptors?

Answer 18

B2 and B1

Question 19

What is icatibant?

Answer 19

A selective B2 receptor antagonist for angioedema (a condition where patients produce elevated levels of bradykinin due to C1 esterase inhibitor deficiency)

Question 20

Does acetylcholine cause vasodilation or vasoconstriction?

Answer 20

Both - if the endothelium is present it causes vasodilation at a lower concentration and vasoconstriction at a higher concentration, if the endothelium is absent it causes vasoconstriction

Question 21

What is endothelium-derived relaxant factor?

Answer 21

NO - this is what makes acetylcholine cause vasodilation when endothelium is present

Question 22

What are endothelium derived vasoactive factors?

Answer 22

Factors released from the endothelium which cause relaxation or contraction - e.g. prostacyclin, NO and EDHF cause relaxation and endothelin causes contraction

Question 23

How do ACh and bradykinin receptors cause the generation of NO?

Answer 23

Receptor activation and mechanical stress leads to elevation in calcium levels, calcium stimulates NOS, NOS makes NO from arginine, NO diffuses from endothelium to smooth muscle, NO activates guanylate cyclase in smooth muscle which causes synthesis of cGMP - leads to muscle relaxation

Question 24

What are the three isoforms of NOS?

Answer 24

nNOS in nerves and epithelial cells, iNOS in macrophages and smooth muscle, eNOS in endothelial cells

Question 25

What is the action of NOS inhibitors?

Answer 25

vasoconstriction and hypertension

Question 26

What is L-NAME?

Answer 26

N-nitro-L-arginine methyl ester - a NOS inhibitor

Question 27

What is the physiological role of NO?

Answer 27

Flow dependent vasodilation, inhibiting platelet adhesion and aggregation, neurotransmitter