resp pharmacology quick Flashcards
what does ACh on M3 receptors in the airway cause
Gq
stimulates phospholipase C
contraction
what does adrenaline on B2 receptors in airway cause
Gs stimulates adenylyl cyclase ATP --> cAMP --> PKA PKA phosphorylates \+ inhibits MLCK \+ stimulates myosin phosphatase relaxation
how does calcium initiate relaxation in a SMC
joins with calmodulin to form Ca2+-calmodulin
what does ca2+-calmodulin do
converts inactive MLCK into active MLCK
what does active MLCK do
converts inactive myosin cross bridge into phosphorylated myosin cross bridge (binds actin)
phosphorylation of regulatory MLC in the presence of elevated intracellular Ca2+ and ATP —->
contraction
dephosphorylation of MLC by myosin phosphatase —>
relaxation
in the presence of elevated intracellular Ca2+, what is greater - the rate of phosphorylation or the rate of dephosphorylation
rate of phosphorylation
true/false
relaxation requires return of intracellular Ca2+ to basal level
true - primary and secondary active transport
what does myosin light chain kinase do
dephosphorylated inactive MLC —> phosphorylated active MLC
relaxation —> contraction
what does myosin phosphatase do
phosphorylated active MLC —> dephosphorylated inactive MLC
contraction —> relaxation
give 5 characteristics of chronic asthma
increased mass of SM (hyperplasia and hypertrophy) accumulation of interstitial fluid increased secretion of mucus epithelial damage sub-epithelial fibrosis
what does epithelial damage cause
exposed sensory nerve endings (c-fibres) - hypersensitivity
what kind of hypersensitivity is asthma
Type 1 (delayed phase is type 4 but in general type 1)
what is the immediate phase of asthma
bronchoconstriction - hyperresponsiveness
what is the delayed phase of asthma
inflammation
what happens when a non-atopic individual encounters an allergen
phagocytosis of allergen by dendritic cell
low level Th1 response
what kind of immunity is it when a non-atopic individual meets an allergen
cell mediated
IgG and macrophages
what happens when an atopic person encounters an allergen
phagocytosis by dendritic cell
strong Th2 response
what kind of immunity is it when an atopic individual meets an allergen
anti-body mediated
IgE
what happens in severe asthma
Th1 also contributes
how does the antigen presenting cell present to Th cells
MHC class II
what does Th2 produce that activates B cells
IL4
also by binding to them
what do the activated B cells do
mature to plasma cells that secrete IgE
what IL activates eosinophils
IL5
what IL activates mast cells to express Fc receptors
IL4 and IL13
what does cross linking of IgE receptors cause
Ca2+ entry into mast cell and release of Ca2+ from intracellular stores
what does Ca2+ entry into mast cell and release of Ca2+ from intracellular stores cause
release of secretory granules containing preformed histamine
release of LTC4 and LTD4
release of LTB4, PAF, PGD2
what do LTC4 and LTD4 cause
airway smooth muscle contraction
increased vascular permeability
mucous secretion
what do LTB4, PAF and PGD2 cause
attract cells causing inflammation e.g. eosinophils, lymphocytes,
what do glucocorticoids do
basically decrease everything inflammatory
increase B2 receptors
how do glucocorticoids increase transcription of anti-inflammatory genes
HATs (histone acetyl transferases)
how do glucocorticoids decrease the transcription of inflammatory genes
HDACs (histone deacetyl transferases)
where are M1 found
ganglia
where are M2 found
post ganglionic neurone terminals
where are M3 found
ASM
mucus secreting cells
what M receptor
facilitates fast neurotransmission mediated by ACh acting on nicotinic receptors
M1
what M receptor
mediates contraction due to ACh
M3
what M receptor
evokes increased mucus secretion
M3
what M receptor
is an inhibitory auto receptor reducing release of ACh
M2
what would a blockade of M2 cause
increase ACh release
what immune cells are involved in COPD
neutrophils
CD8+ t cells
increased macrophage numbers
what do the immune cells in COPD cause
release of matrix metalloproteins
e.g. elastase, free radicals
what does smoking/air pollutants cause
stimulation of resident alveolar macrophages –> cytokine production
where is the synapse of the vago-vagal reflex and what nerve is involved
CNX
brainstem
what causes the immediate phase response of asthma attack
release of spasmogens from mast cells
what causes the delayed phase response in asthma attack
release of substances that attract inflammatory cells
LTB4, PAF and PGD2
where are glucocorticoids released from
zona fasiculata
true/false
glucocorticoids can resolve established inflammation
true
where are mineral corticoids released from
zona glomerulosa
what is the term for distension and damage to alveoli, destruction of acinal pouching in alveolar salsa and loss of elastic recoil in COPD
emphysema
