Respiratory disease and their treatment Flashcards Preview

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Flashcards in Respiratory disease and their treatment Deck (69):
1

what mechanisms increase free intracellular calcium

- voltage gated calcium channels - phospholipase C/inositol trisphosphate - releases from intracellular stores

2

endogenous mediators for airway smooth muscle contraction

- ACh - histamine - Leukotrienes - LTC4 and LTD4

2

major cytokines of slow response of mast cell activation

IL-4, IL-5, GM-CSF

2

main mediators involved in COPD

LTB4, IL-8, TNF-alpha, ROS+++

3

what effects are controlled with relievers, controllers and preventers

- airway SM bronchoconstriction - treated with relievers, controllers and preventers - bronchial wall oedema and mucus hypersecretion - can only be treated with prenters

4

what is the action of leukotriene B4

promotes inflammation by attracting leukocytes

5

how is the B2 adrenoceptor downregulated

- decreased mRNA stability - receptor protein degradation - decreased rate of transcription

6

intrinsic stimuli for mast cell activation

C5a neuropeptides osmotic stimuli hypertonic stimuli

7

main genes turned off with GCS and their actions

- cytokines - inducible enzymes for inflammatory mediators (PLA2, iNOS, COX-2) - adhesion molecules (ICAM-1, E-selectin)

8

drugs that are LABAs

salmeterol - slow onset, 12 hour duration formoterol - rapid onset, 12 hour duration indacaterol - rapid onset, 24 hour duration

8

mediators in the rapid response of mast cell activation

cysteine-leukotrienes and PGD2

9

what blocks the actions of cysteinyl leukotrienes

luekotriene antagonists (monteleukast)

9

how do GCSs have their effects

- transactivation - activation of anti-inflammatory genes - transrepression - ligand-bound GR engages and inhibits inflammatory genes

10

when are H1 receptor antagonists indiciated

- uticaria - atopic dermatitis - hayfever - anaphylaxis and angioedema - bites and stings - motion sickness -NOT INDICATED FOR ASTHMA OR COLDS

10

treatment of PAH

endothelin receptor antagonists prostanoids phosphodiesterase inhibitors

12

what holds the small airways open

parenchymal tethering - stretch further opposes shortening of SM

13

3 classes of H1 receptor antagonists

sedative non-sedative (caused long QT) new non-sedative

13

side effects of oral GCS

- osteoporosis - diabetes - muscle wasting - hypertension - growth suppression - suppression of adrenal/pituitary/hypothalamic axis

14

definition of asthma

a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness

14

histological changes of an asthmatic epithelial cell

- goblet cell metaplasia - subepithelial collagen thickening of BM - infiltration of inflammatory cells - increased mucosal vascularity - increased smooth muscle volume - epithelial damage

14

How do SABAs work

activate B2 adrenoceptor - activates Gs - stimulates cAMP --> activates PKA: - activates SERCA - inhibits IP3R Leads to reduced cytoplasmic Ca and therefore less MLCK activation

14

action of muscarinic receptor antagonists

prevent manifestations of reflex airway obstruction - less effective than beta-2 agonists

15

pharmacological inhibitors of mast cell activation

disodium cromoglycate nedocromil sodium

16

side effects of inhaled GCS

- dysphonia -oral candidiasis - decreased serum cortisol

18

what happens to the B2 adrenoceptor one sequestrated

either dephosphorylated and recycled or degraded and lost

20

drugs that are SABAs

salbutamol terbutaline

21

actions of phosphodiesterase inhibitors

- PDE inhibition - smooth muscle relaxant - adenosine antagonism - HDAC 2 activation

22

how are cysteinyl leukotrienes made

AA --> 5-HPETE (by 5-lipoxygenase) 5-HPETE --> LTA4 --> LTC4 (by glutathione S-transferase)

23

side effects of theophylline

nausea, vomiting, diarrhoea, CNS stimulation, dysrythmias

24

when do you use LABAs on patients

in combination with GCS - used as monotherapy - linked to increased morbidity and mortality

25

main cells involved in asthma

mast cells eosinophils CD4 T cells macrophages

27

extrinsic stimuli for mast cell activation

- allergen (IgE) - polybasic drugs - mechanical stimulation - UV light/heat

28

action of disodium cromoglycate and nedocromil sodium

- only modestly anti-inflammatory - reduction in mast cell degranulation, C-fibre activation and eosionophil activation - cause annexin-1 release --> resolves inflammation

30

mechanisms decreasing free intracellular calcium

- plasma Ca ATPase - extrusion across the plasma membrane - Sarcoplasmic SERCA - uptake into internal stores

30

when are GCS indicated

- using b2 agonist >3 times a week - FEV1

31

why do local mediators only act locally?

they are quite labile they are rapidly metabolised close to their site of release

33

what are the inflammatory effects of asthma

- mucus hypersecretion and hyperplasia - vasodilation - plasma leak - oedema - epithelial shedding - bronchoconstriction - SM hypertrophy, hyperplasia - subepithelial fibrosis - sensory nerve activation

33

main cytokines of the delayed phase of mast cell activation

CSF, TNF, chemokines

35

duration of action of SABAs is dependent on

perfusion of the lung - not by metabolism

36

main cells involved in COPD

neutrophils CD8 T cells macrophages +++

38

how is phosphorylation of beta-2 adrenoceptor achieved

by PKA and beta adrenergic receptor kinase - also enhances binding of B-arrestin

38

what produces cysteinyl leukotrienes?

eosinophils, mast cells and macrophages

39

main mediators involved in asthma

LTD4, histamine, IL-4, IL-5, ROS

40

onset of SABAs

rapid - 2-5 minutes

42

mediators in the immediate response of mast cell activation

histamine, heparin, tryptase, TNF-alpha

43

what is the pharmacological treatment for inhibiting mediator production in allergy

glucocorticoids --> reduce mast cell cytokine production

44

adverse effects of SABAs

tachycardia, tremor, hypokalemia

45

when is pharmacological treatment indicated with pharmacological mast cell activation inhibition

indicated for treatment of allergic responses of mucosal surfaces

46

results of immediate phase of the mast cell responses

- pain and itch (sensory nerve activation) - bronchospasm - mucus secretion - vasodilation - hypotension - increased vascular leak of endothelium - hypovolemia - positive inotropic and chrontropic effects - gastic acid secretion - CNS - increased w

47

when is 5-lipoxygenase activated

by an increase in intracellular Ca by stimuli produced in infection, allergic responses ans other forms of inflammation

49

what types of pharmacological drugs inhibit mediator actions

H1 receptor antagonists cysteinyl leukotriene receptor antagonists

50

what are ITAMS

immunoreceptor Tyrosine-based Activation MotifS

51

result of activation of CysLT1 R

- hypotension during anaphylactic shock - vasodilator in skeletal muscle - decreased CO - hypovolaemia - airway obstruction in asthma - nasal obstruction in hayfever

52

3 phases of mast cell responses

- immediate - rapid - slow

54

where does LTC4 and metabolites act

on Cys-LT1 Receptor

54

action of cysteinyl leukotriene receptor antagonists

bronchodilation

55

4 targets for anti-allergic drugs

- inflammatory cell activation - mediator production - mediator action - prevention and desensitisation

56

regulation of airway smooth muscle contraction performed by

- protein kinase A - activates myosin light chain phosphatase - Rho kinase - inhibits myosin light chain phosphatase - protein kinase c - inhibits myosin light chain phosphatase

57

examples of cysteinyl leukotriene receptor antagonists

zafirlukast montelukast

58

what are examples of muscarinic receptor antagonists used in asthma

ipratropium bromide - non selective tiotropium bromide - M3 selective

59

regulation of beta-2 adrenoceptors achieved by: (3)

- phosphorylation (seconds) - sequestration (minutes) - downregulation (hours)

61

endogenous inhibitors of mast cell activation

PGE2 adrenaline crotisol

63

cysteinyl leukotriene receptor antagonists indicated for

- aspirin-induced asthma - exercise-induced asthma - combination therapy - allergic rhinitis

64

endogenous mediators for airway smooth muscle relaxation

- adrenaline - PGE2 - PGI2

65

main genes turned on with GCS and their actions

B2-adrenoceptor - more Rs to initiate SM contraction Annexin-1 - anti-inflammatory serpin A3 - inhibitor of serum proteases

66

drugs that are phosphodiesterase inhibitors

theophylline roflumilast

67

actions of glucocorticoids in asthma

reductions in: - activity, recruitment and survival of eosinophils and T lymphocytes - activation of mast cell and macrophage cytokine production - in proliferation, cytokine and collagen production by smooth muscle and fibroblasts LEADS TO DECREASE INFLAMMATORY CELL NUMBER AND ACTIVATION

68

mechanism of airways SM bronchoconstriction

increase in calcium -> binds to calmodulin -> activates myosin light chain kinase to phosphorylate myosin light chain -> activation of actomyosin ATPase --> myosin- actin crosslinking and contraction

69

what is the purpose of the slow response of the mast cell response

to set up the environment for infiltration of eosinophils, more mast cells and prolonged survival of these cells