drugs and histamine receptors Flashcards
What 4 conditions occur when inflammation goes wrong?
- Anaphylaxis
- Asthma
- Rheumatoid arthritis
- Atherosclerosis
Which step of inflammation do medicines such as steroid, antihistamines and anti-inflammatory drugs target?
Release of chemical mediators
Which 2 mediators cause vasodilation?
- Histamine
- Prostaglandins (PGE2 & PGI2)
Which 2 mediators cause increased vascular permeability?
- Histamine
- Platelet activating factor (PAF)
Which 4 mediators cause exudation (fluid filtering from circulatory system into the surrounding tissue)?
Plasma proteins:
- Complement
- Coagulation system
- Fibrinolytic system
- Kinin system
What are the 7 principle mediators/autocoids/local hormones of inflammation and allergy?
- Histamine
- Platelet Activating Factor
- Bradykinin
- Nitric Oxide
- Cytokines (interleukins, interferons, chemokines, colony stimulating factors)
- Eicosanoids (prostagladins, thromboxanes, leukotrienes)
- Plasma proteins (kinins, complement, coagulation and fibrinolytic factors)
When are these mediators released?
From cells upon stimulation
How is histamine synthesised?
Decarboxylation of histamine by L-histadine decarboxylase
Which 2 enzymes rapidly metabolises histamine?
n.b. they produce two different products
Histamine-N-methyltransferase
or
Diamine oxidase/histaminase
How many different types of histamine receptor subtypes have been discovered?
4
Which two types of celLs contain histamine contained in granules?
- Mast cells
- Basophils
Which cells in the gastric glands in the gastric mucosa are also found to contain histamine?
Enterochromaffin-like cells (ECL)
In which organs of the body can the highest levels of histamines be found?
Lung
Skin
Brain
GI tract
n.b. they are found throughout the body too!!
Where are mast cells produced?
Bone marrow
(released as immature cell and matures in the tissue)
Which antibody does the FCERI receptor have a high affinity for?
IgE
What are the 4 stages of mast cell degradation?
- Priming of mast cells (body produced IgE = bind mast cells = chemical mediator release)
- 2nd exposure to allergen = IgE bind to mast cell surface
- Activates mast cell (granule movement and fusion to membrane due to increased Ca)
- Degranulation (release of chemical mediators)
Which two other factors can activate mast cells?
Complement components:
C3a
C5a
Which process gets the complement & phagocytes present mainly in the blood to the site of tissue invasion?
Inflammatory response
What 2 things can cause histamine release?
- Some neuropeptides (e.g. substance p)
- certain basic drugs (e.g. morphine & tubocurarine)
n.b. some basic drugs e.g. morphine and other opioids can displace histamine from mast cells without activating cell surface receptors
What inhibits histamine release?
An increase in cAMP
e.g. by beta adrenoreceptor agonists
What are the 3 physiological roles of histamine?
- local immune response (tissue repair, inflammation, control of local blood flow, allergies & anaphylaxis)
- regulates physiological function in the gut (increased gastric acid secretion = H2)
- Neurotransmitter in CNS
Why is the reaction to histamine location dependant?
- different histamine receptors
(all GPCRs) = H1, H2, H3 & H4
(located in different tissues & couple different G proteins)
What type of receptor is the H1 receptor?
And where is it found?
GPCR - Gq
= activates PLC & PIP2
Found in smooth m, endothelium & CNS tissue
Activation of the H1 receptor causes (8):
- Bronchial smooth muscle contraction
- vasodilation
- separation of endothelial cells
- increased vascular permeability
- pain and itching
- motion sickness
- allergic rhinitis
- sleep and appetite suppression
