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respiratory > asthma > Flashcards

asthma Flashcards

1
Q

what does coupling to Gs protein cause

A

adenyl cyclase, to form cAMP, which forms PKA which causes relaxation by phosphorylating and activating myosin phosphatase and phosphorylating and inhibiting myosin light chain phosphatase

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2
Q

what do B2 agonsits do in relation to mucus

A

they decrease mucus release and increase mucus clearnace

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3
Q

what are particularly useful in nocturnal asthma

A

LAMA

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4
Q

what do repeated use of B2 agonists do

A

cause desensitisation of B2 adrenoceptors and endocytosis (resulting in loss of function)

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5
Q

what are the 2 kinases involved with repeated activation of B2 adrenoceptors

A

PKA and GRK

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6
Q

what is the difference in PKA and GRk

A

PKA can be phosphorylated even when no agoinst is bound but for GRK to be phosphorylated an agonist must be bound

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7
Q

what does PKA cause

A

reduced G protein coupling

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8
Q

what does GRK cause

A

G protein coupling/endocytosis

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9
Q

give examples of cysteinyl leukotrienes

A

LTC4, LTD4, LTE4

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10
Q

where are LTC4, LTD4 AND LTE4 derived from

A

mast cells and infiltrating inflammatory cells and cause smooth muscle contraction, mucus secretion and oedema

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11
Q

where is arachidonic acid released from

A

released by phospholipase A2 when stimulated by mast cell activation

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12
Q

what does arachidonic acid stimulate

A

mast cell 5-lipoxygenase by FLAP

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13
Q

what are cysLT1s more effective against

A

antigen induced and exercise induced bronchospasm

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14
Q

what is the thought mechanism of action for methyxanthines

A

they inhibit phosphodiesterases

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15
Q

how are methylxanthines and CystLT administered

A

orally

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16
Q

what affect do methylxanthines have

A

anti-inflammatory actions and bronchodilator at high concentrations

17
Q

what side effects can methylxanthines cause

A

at supra therapeutic range they can cause problems with CNX, CVS, GI tract and kidney inc dysrhythmia, seizures and hypotension
also cause nausea, vomiting abdo discomfort and headache at therapeutic range

18
Q

how might theohilline improve the effects of glucocorticosteroids

A

it activates histone deacetylases (HDAC)

19
Q

why are methylxanthines problematic

A

numerous drug interactions involving CYP450s, particularly antibiotics that inhibit CYP450s

20
Q

what is another name for cortisol

A

hydrocortisone

21
Q

why are synthetic derivatives of cortisol/hydrocortisone used in the treatment of asthma

A

they would have both mineralcorticoid and glutocorticoid properties, mineralcorticoid properties are not useful so give endogenous steroids with only glucocorticoid effects

22
Q

do glucocorticoids have a bronchodilator effect

A

no

23
Q

what is the effect of glucocorticoids

A

they decrease inflammation

24
Q

what is expression of inflammatory genes associated with

A

acetylation of histones by HATs, this causes unwinding of DNA form histones allowing transcription

25
Q

what happens when HATS are acitvated

A

the DNA is unwound from its histones allowing transcription

26
Q

do HATs increase or decrease transcription and how

A

the increase transcription as the acetylation unwinds DNA form histones allowing transcription

27
Q

what do glucocorticoids do in relation to gene expression

A

they recruit histone deacetylases HDACs to activated gene and switch off gene transcription

28
Q

what do glucocorticoids prevent

A

prevent allergen induced reflux into lung and cause apoptosis
decrease formation of TH2 cytokines (eg IL4 AND 55) and cause apoptosis
they prevent the production of antibodies in particular IgE

29
Q

what are the cellular effects of glucocorticoids

A
  • decrease the number of inflammatory cells
  • decrease cytokine mediators, -decrease the leaking in the endothelial cell
  • increase B2 receptors -decrease cytokines
  • decrease mucus secretion
30
Q

can glucocorticoids resolve established inflammation

A

yes they prevent inflammation and resolve established inflammation

31
Q

what are the common side effects due to deposition of steroids in the oropharynx

A

dysphonia (hoarse and weak voice), oropharyngeal candidiasis (thrush)

32
Q

what should patients be encouraged to do

A

take sufficient inhaled glucocorticoids to control symptoms and avoid disease progression which may be irreversible

33
Q

what are cromones also known as

A

mast cell stabilisers

34
Q

where do cromones have no direct effect

A

no direct effect upon bronchial smooth muscle

35
Q

what do cromones do

A

decrease in the sensitivity of irritant receptors associated with sensory C-fibres that trigger exaggerated reflexus and reduction of cytokine release

respiratory (4 decks)

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