P: anti-inflammatory drugs 1 - week 5 Flashcards
Describe the 2 ways that chemical signalling occurs between cells, then describe the 3rd way
- release of molecules as secreted mediators
- direct interaction with membrane bound molecules (cell to cell contact)
- Hybrid mechanism: Exosomes - little lipid-lined vesicles that contain proteins on lipid membrane, and also have various nucleic acids inside them
Name 5 important local mediators
- histamine (a small amine)
- prostaglandins
- leukotrienes
- bradykinin
- nitric oxide
note: prostaglandins and luekotrienes are eicosanoids
Why would a local mediator usually only act locally?
often they are quite labile or are rapidly broken down close to the site of release
Name 4 modulatory functions of local mediators
- smooth muscle tone/length
- glandular secretion
- permeability (cascular and airway)
- sensory nerves (pain and itch)
Where is the major source of histamine in the body?
Mast cells
where are mast cells found? Where are they most abundant?
found in pretty much every tissue/organ in the body. Most abundant at sites that came into contact with the external environment (e.g. skin, resp. tract)
Where in the mast cells is histamine stored? How can we see this?
In electron microscopy you’ll see that the mast cells have these densely stained granules. And histamine is found/stored within these granular matrices
What is de-granulation of mast cell?
When there’s a stimulus for the mast cell, de-granulation occurs. This is where these granules fuse with the plasma membrane of the cell, and release their contents (i.e. HISTAMINE) out into the extracellular environment
Describe the process of allergic inflammation with mast cells
The body produces IgE, which reacts with allergens. IgE is ralied against these substances and it binds to the surface of mast cells via this high affinity IgE receptor called FCeR1
How high or low is FCeR1 afinity for IgE?
High
What happens to the mast cellwhen IgE is produced against an allergen?
the IgE binds and “sensitizes” the mast cell. Results in de-granulation of the mast cell and release of the histamine
How does histamine mediate its activities?
through interacting with 4 receptors (H1, H2, H3, H4)
Which histamine receptor should you target for allergic inflammation tx?
use H1 receptor antagonists. This will prevent histamine from acting on the H1 receptor
List the 3 classes of H1 receptor antagonists
- sedative - e.g. chlorpheniramine, promethazine
- non-sedative (poor entry into CNS) - e.g. tefenadine, astemizole
- newwer non-sedative agents - e.g. cetrizine, loratidine
Why were older non-sedative H1 receptor antagonists withdrawn from the market?
because they could cause rare, sudden ventricular arrhythmia
What advantage do newer non-sedative agents of H1 receptor antagonists have over the older ones?
they have a reduced risk of unwanted cardiac effects
What is the brand name for acetylsalicylic acid?
aspirin
What are the 3 main outcomes of salicylate?
- anti-pyretic (fever)
- analgesic (pain)
- anti-inflammatory actions
What is the active component in semen that was able to regulate smooth muscle tone?
Prostaglandins
How many cells produce prostaglandins?
most cells
