Lecture objectives
- Allergic reactions, histamine and antihistamines
- Histamine receptors
- Antihistamine drugs (H1 antagonists)
- Gastric antihistamine drugs (H2 antagonists)
What is inflammation
Histamine and allergic diseases
see allergy and hypersensetivity
Hypersensitivity reactions (type I)
See hypersensitivity
Sensitisation phase
hes talking about the b cell encoutering the allergen and makeing ige antibodies and doing clinal expansion
activation phase
the allergen antibodies attached to the mast calls are activated triggering degranulation
Histamine, a ubiquitous biogenic amine in immunity and physiology
Histamine is structurally related to neurotansmitter like dopamine and serotonin, It is widely districuteed across the body, primary tissue source is the mast cell and in the blood basophils are the source,
Sources of histamine: storage and turnover
there is a slow and fast turnover pool
slow stores large amounts and releases it
fsat does not store histamine and instead just make
Histamine receptors
there are 4 and they are GPCRs
H1 is involved in allergy, inflammetion, and smooth muscle contraction
H2 regulates Gastric acid secretion
H1 and H2 are the main targets of antihistamines
H1 receptors
- Cause increase in intracellular calcium
- smooth muscle contraction
- Increased vascular permeability
Functions and location
Vascular endothelium
Increases vasodilation and vascular permability
contributes to swelling, redness and hypotension
Bronchcial endothelium
Causes constriction, contributing to asthma symptoms
Sensory nerve endings
Triggers itching and pain
Histamine effects from H1
Dilates blood vessels
contracts intestinal and bronchial smooth muscle
increases bascular permability and oedema
sensetises afferent nerve terminals
neurotransmitter that increases wakefullness
Triple response
The effects of histamine may be seen in the triple response. this is the 3 things that happen with a localised allergic reaction (eg a prick test).
They are
- wheal
- flare
- Itch
H2 receptors
Functions and locations:
Stomach (parietal cells)
stimulates HCL secretion via H+/K+ ATPase activation
Cardiovascular (cardiac muscle)
Increases heartrate and cardiac output
Histamine effects (H2)
Stimulates secretion of gastric acid
Increases cardiac rate and output
Antihistamines
H1 antihistamines
H1 antihistamines are antiallergy drugs. Some examples include:
- Fexofenadine (Telfast), cetirizine (zyrtec) (2nd gen, non-sed)
- Diphenhydramine (benadryl) (1st gen, sed)
These drugs are competitive antagonists at H1 receptors
The side effects are:
- anticholinergic effects
- Sedation
Indications are:
allergic rhinitis, acute urticaria (hives) - hay fever - insect bits - Conjunctivitis
Some 1st gen antihistamines (benadryl) are:
Antiemetic agents
Anti-tussive agents
Produce anticholinergic effects in the CNS
Sedative/hypnotic agents
Cromolyn (cromoglicate) is different
It inhibits release of histamine from mast cells
used as a nasal spray
Treatment of motion sickness
Some antihistamines work on the brainstem vestibular nuclei to reduce motion induced nausea and vomiting.
H2 receptors antagonists
Cimetidine, renitidine
main use is to inhibit gastric acid secretion. (peptic ulcers and reflux oesophagitis)
largely omeprazole is used for this,
Summary
AND GUT content