Histaminergic System + Antihistamines Flashcards
What are autacoids?
LOCAL HORMONES
Short acting endogenous mediators usually acting as part of an inflammatory response
What is histamine?
Endogenous substance synthesised, stored + released by professional histamine cells
What are the histamine cells?
Mast cells
Basophils
Some neurons in CNS + PNS
What histamine synthesised by?
Decarboxylation from histidine
Where is histamine stored?
In granules in mast cells, basophils + enterocytes
When is histamine released?
Response to certain stimuli
What is histamine eliminated by?
Oxidative deamination +/ transmethylation
How does the histamine process work?
L-amino acid transporter
Histidine converted to histamine
By histidine decarboxylase
Vesicular monoamine transporter
Histamine methyltransferase released
To form tele-methylhistamine
What are the histamine receptors?
H1 = allergy
H2 = acid reflux
H3 = CNS
H4 = inflammation + itch
Where are H1?
Smooth muscle
Endothelium
CNS
Where are H2?
Gastric parietal cell
Vascular smooth muscle cells
Basophils
Where are H3?
CNS cells
Peripheral NS
Where are H4?
Bone marrow
White blood cells
What do H1 do?
Bronchoconstriction
Vasodilation
Allergic rhinitis
Pain + itching
What do H2 do?
Gastric acid secretion
Vasodilation
Inhibition of IgE-dependent degranulation
What do H3 do?
Presynaptic
Feedback inhibition of histamine synthesis
What do H4 do?
Mediate mast cell chemotaxis
What is H1 G-protein coupled receptor?
Gq coupled to phospholipase C (PLC)
What is H2 G-protein coupled receptor?
Gs coupled to adenyl cyclase (AC)
What is H3 G-protein coupled receptor?
Gi/o coupled to AC
What is H4 G-protein coupled receptor?
Gi/o in mast cells
What is the response to histamine in the skin?
Initial red line
Flare
Wheal
What is the response to injected intradermally histamine?
Red spot
Flare
Wheal
What effect does histamine have on the heart?
Cardiac contractility + electrical events
Increases force of contraction by promoting Ca2+ influx
What effect does H1 have on the lungs?
Bronchoconstriction, increased mucus viscosity
Stimulation of vagal sensory nerve endings = cough
What effect does H2 have on the lungs?
Slight bronchodilation, increased mucus sceretion
What is the effect of histamine on peripheral vascular resistance?
Decreases
What is the effect of histamine on vascular permeability?
Increases
What does histamine (H3) stimulate?
Nerve endings (pain)
Describe type I allergic response?
IgE Abs
IgE binds to mast cells/basophils
Ab binds antigen = release of histamine
Describe what happens in anaphylaxis
Decreased BP
Decreases cardiac output
Bronchoconstriction + increased pulmonary secretions
Pruritis
What is the treatment for anaphylaxis?
Epinephrine = physiological antagonist of histamine
What are the 3 mechanistically different approaches to minimise histamine reactions?
Physiological antagonism
Inhibit release of histamine
Pharmacological antagonism
