Histaminergic System + Antihistamines

Question 1

What are autacoids?

Answer 1

LOCAL HORMONES
Short acting endogenous mediators usually acting as part of an inflammatory response

Question 2

What is histamine?

Answer 2

Endogenous substance synthesised, stored + released by professional histamine cells

Question 3

What are the histamine cells?

Answer 3

Mast cells
Basophils
Some neurons in CNS + PNS

Question 4

What histamine synthesised by?

Answer 4

Decarboxylation from histidine

Question 5

Where is histamine stored?

Answer 5

In granules in mast cells, basophils + enterocytes

Question 6

When is histamine released?

Answer 6

Response to certain stimuli

Question 7

What is histamine eliminated by?

Answer 7

Oxidative deamination +/ transmethylation

Question 8

How does the histamine process work?

Answer 8

L-amino acid transporter
Histidine converted to histamine
By histidine decarboxylase
Vesicular monoamine transporter
Histamine methyltransferase released
To form tele-methylhistamine

Question 9

What are the histamine receptors?

Answer 9

H1 = allergy
H2 = acid reflux
H3 = CNS
H4 = inflammation + itch

Question 10

Where are H1?

Answer 10

Smooth muscle
Endothelium
CNS

Question 11

Where are H2?

Answer 11

Gastric parietal cell
Vascular smooth muscle cells
Basophils

Question 12

Where are H3?

Answer 12

CNS cells
Peripheral NS

Question 13

Where are H4?

Answer 13

Bone marrow
White blood cells

Question 14

What do H1 do?

Answer 14

Bronchoconstriction
Vasodilation
Allergic rhinitis
Pain + itching

Question 15

What do H2 do?

Answer 15

Gastric acid secretion
Vasodilation
Inhibition of IgE-dependent degranulation

Question 16

What do H3 do?

Answer 16

Presynaptic
Feedback inhibition of histamine synthesis

Question 17

What do H4 do?

Answer 17

Mediate mast cell chemotaxis

Question 18

What is H1 G-protein coupled receptor?

Answer 18

Gq coupled to phospholipase C (PLC)

Question 19

What is H2 G-protein coupled receptor?

Answer 19

Gs coupled to adenyl cyclase (AC)

Question 20

What is H3 G-protein coupled receptor?

Answer 20

Gi/o coupled to AC

Question 21

What is H4 G-protein coupled receptor?

Answer 21

Gi/o in mast cells

Question 22

What is the response to histamine in the skin?

Answer 22

Initial red line
Flare
Wheal

Question 23

What is the response to injected intradermally histamine?

Answer 23

Red spot
Flare
Wheal

Question 24

What effect does histamine have on the heart?

Answer 24

Cardiac contractility + electrical events
Increases force of contraction by promoting Ca2+ influx

Question 25

What effect does H1 have on the lungs?

Answer 25

Bronchoconstriction, increased mucus viscosity Stimulation of vagal sensory nerve endings = cough

Question 26

What effect does H2 have on the lungs?

Answer 26

Slight bronchodilation, increased mucus sceretion

Question 27

What is the effect of histamine on peripheral vascular resistance?

Answer 27

Decreases

Question 28

What is the effect of histamine on vascular permeability?

Answer 28

Increases

Question 29

What does histamine (H3) stimulate?

Answer 29

Nerve endings (pain)

Question 30

Describe type I allergic response?

Answer 30

IgE Abs IgE binds to mast cells/basophils Ab binds antigen = release of histamine

Question 31

Describe what happens in anaphylaxis

Answer 31

Decreased BP Decreases cardiac output Bronchoconstriction + increased pulmonary secretions Pruritis

Question 32

What is the treatment for anaphylaxis?

Answer 32

Epinephrine = physiological antagonist of histamine

Question 33

What are the 3 mechanistically different approaches to minimise histamine reactions?

Answer 33

Physiological antagonism Inhibit release of histamine Pharmacological antagonism