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Flashcards in Histamine Deck (31):
1

What is the basic structure of histamine

It is a basic amine formed from histidine (amino acid)

2

What cell types is histamine found in

Mast cells
Basophils
Paracrine (mast-like) cells
Neurones

3

Where is histamine mainly stored

Mast cells

4

How is histamine mainly stored

In intracellular granules. In a complex with heparin and an acidic protein

5

What is the mechanism of histamine release from mast-cells

Allergen bound to IgE on surface of mast-cell. Allergen-IgE interaction leads to cytosolic calcium increase. This promotes exocytosis of secretory granule contents -> Histamine.

6

How many subtypes of histamine are there

4
(H1-4)

7

How does histamine affect signalling mechanisms in cells

Through interaction with GPCRs/ G proteins

8

How does Histamine H1 affect signalling mechanisms

Activates phospholipase C. Produces IP2 and DAG.
Activates PKC and increases cytosolic calcium levels.

9

How does Histamine H2 affect signalling mechanisms

Activates adenylate cyclase. Produces cAMP. Activates PKA.

10

How do Histamine H3 and H4 affect signalling mechanisms

Inhibit adenylate cyclase. Decreases cAMP levels. Deactivates PKA

11

What are the three stages of the histamine response and what causes them

Flush - dilates small arterioles
Wheal (lump) - increases permeability of post capillary venules. Allows plasma fluid leakage
Flare - acts on sensory nerve terminals. Triggers electrical impulses. Causes release of peptide that causes vasodilation.

12

What are the main pharmacological effects of histamine

Vasodilation (H1+2)
Increased heart rate and force (H2)
Bronchoconstriction (H1)
Smooth muscle constriction (H1)
Acid secretion in stomach (H2)
Regulation of immune cells (H1-4)

13

How do the histamine (H1) receptors cause vasodilation

Receptors are on endothelial cell. Can activate:
Endothelial NO synthesis/release; causes smooth muscle relaxation
Endothelial cell contraction; causes increased vascular permeability. Allows plasma and protein leakage into tissues.

14

How do the histamine (H2) receptors increase heart rate/force

Receptors are on 'pacemaker' and muscle cell of heart. Increases firing rate (pacemaker) and contractility (muscle).
Indirectly, vasodilation causes low blood pressure; activates baroreceptor reflexes; increases sympathetic drive on heart.

15

How do the histamine (H2) receptor mediate acid secretion in the stomach

Receptors on gastric pariental cells cause HCl and pepsin secretion by cells

16

What role do histamine receptors play in the CNS

Histamine released from histaminergic nerves in the CNS.
Involved in control of vomiting reflex (+other functions)
Some H1 receptor antagonists have anti-emetic and sedative effects
Regulate release of neurotransmitters (H3)

17

What is Urticaria

Raised itchy/painful rash that migrates. AKA nettle rash/hives.
Type 1 hypersensitivity

18

What is atopic eczema

Chronic relapsing itchy disease of skin. AKA atopic dermatitis
Type 1 hypersensitivity

19

What are H1 receptor antagonists used to treat

Type 1 allergic reactions.
E.g. Hay fever, rashes, insect stings/bites
NOT good for bronchial asthma because other factors are involved

20

Give examples of H1 receptor antagonists

Mepyramine/promethazin. Crosses the blood/brain barrier. Can cause drowsiness because receptors are present in the brain too.
Loratidine/cetirizine.
More modern. Don't enter CNS.

21

What causes anaphylactic shock and how is it treated

Caused by large-scale histamine release. Causes life-threatening fall in bp.
Treated with adrenaline (causes bronchodilation (beta2 receptors) and vasoconstriction (alpha1 receptors)). H1 receptor antagonist can also be used afterwards.

22

What are the two types of hormone released by the GI tract

Endocrine (e.g. gastrin)
Paracrine (e.g. histamine

23

What are the main stomach secretions

Pepsinogen (from chief/peptic cells)
HCl (from parietal cells)

24

What are the main three stimuli that act on the parietal cells

Gastrin
Acetylcholine
Histamine

25

How does histamine stimulate parietal cells

Acts on the histamine (H2) receptors.
Receptors are more sensitve than H2Rs on blood vessels.

26

What are the clinical uses of H2 receptor antagonists

Can reduce acid secretion so can treat: peptic ulcer, reflux oesophagitis and Zollinger-Ellison syndrome
Can also promote healing of duodenal ulcers

27

What are thought to cause peptic ulcers

Not fully understood. Infection of Helicobacter pylori is a major cause. Also a shift in the balance between mucosal damaging/protecting mechanisms plays a role

28

How can a H2 receptor antagonist work to treat problems

Competitively inhibit H2 receptors, so inhibit gastric acid secretion. Can reduce acid secretion by 90%+

29

Give an example of an H2 receptor antagonist

Cimetidine/Ranitidine. (also now nizatidine and famotidine)

30

Name some side effects of H2 receptor antagonists

Diarrhoea, dizziness, muscle pains, rashes.
Sometimes also decreased sexual function and confusion.

31

What are the specific side effects of the H2R antagonist Cimetidine

Cimetidine inhibits the enzymes in the liver (cytochrome P450) that inactivate many drugs and limit duration/strength of drug action.
Without these enzymes, drug metabolism many be delayed and pharma effects increased.
E.g. Warfarin (anti-coagulant) can cause internal bleeding if used in conjunction.