Pharmacology Flashcards
what type of fibres does the vagus nerve carry
preganglionic fibres
what mediated bronchial smooth muscle contraction
ACh acting on M3 muscarinic ACh receptors
what mediates increased mucus secretion
ACh acting on M3 muscarinic ACh receptors
what do bronchial contraction and increased mucus secretion cause
increased airway resistance
through what receptor does the sympathetic division relax smooth muscles
β2-adrenoceptors activated by adrenaline released from the adrenal gland
what does β2-adrenoceptors mediate
decreased mucus secretion
increased mucociliary
reduce air way resistance
how does asthma cause airway narrowing
inflammation
bronchoconstriction
decrease FEV1 and PEFR
what are the two components of neurogenic inflammation
hypersensitivity and hyperreactivity
what is the first stage of development of allergic asthma
initial presentation of an antigen (e.g. dust mite or pollen) initiates an adaptive immune response
what are the steps of the induction phase
1 - aeroallergen breaches airway epitheliumt
2 - allergen processed by CD4+
T cell
3 - becomes Th0 cell
4 - Th0 cell preferentially mature to Th2 cells that produce a cytokine environment
5 - Th2 cells activate B cells by binding to them and by IL-4 production
6 - B cells mature to IgE secreting P cells
What are the two parts of the induction phase
Antigen presentation
Clonal expansion and maturation
what is the second stage of development of allergic asthma
effector phase
what are the stages of the effector phase
1 - Eosinophils differentiate and activate in response to IL-5 released from Th2 cells
2 - Mast cells in airway tissue express IgE receptors in response to IL-4 and IL-13 released from Th2 cells
what is the third stage of development of allergic asthma
subsequent presentation of antigen
what do cross linked IgE receptors stimulate
- calcium entry into mast cells
- release of Ca2+ from intracellular stores
what does the release of calcium from intracellular stores cause
- release of secretory granules containing histamine and the production and release of other agents that cause airway smooth muscle contraction
- release of substances that attract cells causing inflammation into the area
what happens in the immediate phase of asthma
- stimulus
- mast cell degranulation
- bronchospasm caused by spasmogens-chemical e.g. histamine
- chemotaxins attract inflammatory cells (Th2) cells into the area
- chemokines activate cells
- leads to late phase
what happens in the late phase of asthma
- infiltration of releasing TH2 cells and monocytes
- activation of inflammatory cells e.g. eosinophils
- Eosinophils release proteins damaging to airway structure
- Proteins cause shedding of airway i.e. epithelial damage
what is the mechanism of action of beta2 adrenoreceptor agonists
1 - Drug attaches to receptor 2 - Increased Gs secretion 3 - Increased Adenylyl cyclase release 4 - AC reacts with ATP to form cAMP 5 - cAMP inhibits release of PDE 6 - cAMP stimulates release of PKA 7 - PKA phosphorylates MLCK 8 - Relaxation
what does persistent activation of beta2 adrenoceptors cause
receptor desensitisation
endocytosis
results in loss of function
what are the two kinase involved in beta2 adrenoceptors agonist drug mechanisms
protein kinase A (PKA) and G protein receptor kinases (GRKs)
stages of phosphorylation and endocytosis by GRK
1 - Agonist binds 2- Phosphorylation by GRK 3 - G-protein coupling stops 4 - Binding of B-arrestin 5 - Pit is formed 6 - Pit buds off and comes vesicle 7 - B-arrestin unbinds from vesicle EITHER 8 - vesicle is targeted for degradation by lysosomes OR 9 - recycling vesicle
what do beta2 adrenoceptor agonists do
increase mucous clearance
decrease mediator release from mast cells and neutrophils