Pharmacology Flashcards
What does a Gs subunit of a GPCR do?
stimulate adenylate cyclase and increase cAMP production and PKA activation
What does a Gq subunit do?
Stimulate phospholipase C, and increase IP3 and diacylglycerol leads to PKC activation and calcium release from the endoplasmic reticulum.
What does Gi/o subunit do?
inhibit adenylate cyclase, decrease cAMP production, Beta-Gamma subunit inhibits calcium ion channels and activates potassium ion channels.
Examples of ionotropic receptors?
- serotonin= 5-HT3 receptors
- ATP= P2X receptors
- Acetylcholine= nicotinic receptors
What happens when an inflammatory response goes wrong?
- Type I hypersensitivity
- Airway disorders
- autoimmune haemolytic anaemia- dogs
- sweet itch- horses
What are some of the principle mediators of inflammation
Histamine, Bradykinin, nitric oxide, cytokines= interleukins, interferons, chemokines, colony-stimulating factors; Eicosanoids= prostaglandins, thromboxanes, leukotrienes; other plasma proteins= complement, coagulation and fibrinolytic factors; platelet-activating factors, Neuropeptides
What are the main vascular responses to inflammation?
- Vasodilation
- Increased vascular permeability
- Exudation
Where are mast cells produced?
bone marrow, released as immature cells and mature in the tissues.
where are mast cells found?
-beneath the skin, throughout the respiratory system, digestive and urinary tracts
What receptor do mast cells express?
FcεRI with a high affinity to IgE
What are the roles of histamine?
- tissue repair and inflammation
- control of local blood supply- vasodilation and vascular permeability
- contributes to allergic and anaphylactic reactions
- neurotransmitters in the CNS
- Gastric acid secretion
where is histamine found?
- Throughout the body but in high concentrations around the lungs, skin, GIT, and brain= the interfaces between the body and the outer environment.
- Present in mast cells and basophils- that contain granules
- Found in neurones and enterochromaffin-like cells in stomach
What are the steps of Mast cell degranulation?
- Priming of mast cell
- Secondary exposure to the allergen
- Binding of IgE which increases Ca²⁺ concentration in cell
- Migration and fusion of vesicles with cell membrane
- Degranulation
What can inhibit mast cell degranulation?
cAMP
What can cause histamine release?
- neuropeptides
- some basic drugs
How many histamine receptors are there?
4- and they are GPCR
What are the histamine receptors?
- H1
- H2
- H3
- §H4
What does H1 histamine receptor do?
This is the most important in an inflammatory response:
- System vasodilation. ) Increased IP3 and DAG- Stimulate Ca²⁺
- Increased vascular permeability ) ⤴︎
- itching
- bronchoconstriction
- ileum contraction
- effects on neural action potential firing
What does the H2 histamine receptor do?
- Stimulate gastric acid secretion – receptor coupling, increases cAMP
- Relax smooth muscle
- Speed up heart
- inhibit antibody and cytokine production
- inhibit neutrophil activation
What does H3 histamine receptor do?
-Inhibits neurotransmitter release from neurones -> receptor coupling cAMP reduced
What do H4 histamine receptors do?
- Regulates neutrophil release from bone marrow
- mast cell chemotaxis
- receptor coupling reducing cAMP
What are H1 receptor antagonists?
Class of drugs that treat or prevent allergies
orally active and hepatically metabolised
What does a 1st generation H1 receptor antagonist do?
- Able to cross the blood-brain barrier
- 4-6 hours duration, give dose throughout day
What does the 2nd generation H1 receptor antagonist do?
- Can’t cross the blood-brain barrier
- 12-24 hour duration- one tablet lasts for the whole day.