Pharmacology - Asthma

Question 1

where are cell bodies of preganglionic fibres located

Answer 1

brain-stem

Question 2

parasympathetic stimulation of postganglionic cholinergic fibres causes…
(2)

Answer 2

bronchial smooth muscle contraction (mediated by ACh receptors)
increased mucus secretion

Question 3

parasympathetic stimulation of postganglionic nonchilinergic fibres causes…

Answer 3

bronchial smooth muscle relaxation (mediated by NO vasoactive intestinal peptide)

Question 4

sympathetic stimulation causes…

4

Answer 4

bronchial smooth muscle contraction (activated via adrenaline)
decreased mucus secretion
increased mucocilary clearance
vascular smooth muscle contraction

Question 5

increase in concentration of calcium in smooth muscle causes…

Answer 5

depolarisation to occur

Question 6

how calcium initiates contraction in smooth muscles

Answer 6

calcium bound calmodulin > activates Myosin light chain kinase > phosphorylates and activates myosin cross bridge > binds to actin > smooth muscle contraction occurs

Question 7

how contraction of smooth muscle occurs

Answer 7

dephosphorylation of myosin light chain (on myosin cross bridge) by myosin phosphatase

Question 8

examples of causes of asthma attacks

4

Answer 8

allergens
exercise
respiratory
smoke/dust/environmental pollutants

Question 9

asthma is…

Answer 9

intermittent attacks of bronchoconstriction

Question 10

symptoms of asthma

4

Answer 10

tight chest
wheezing
difficulty in breathing
coughing

Question 11

chronic asthma

Answer 11

involves pathological changes to bronchioles from long standing inflammation

Question 12

pathological changes which occur in relation to chronic asthma
(5)

Answer 12

increased smooth muscle mass (hypertrophy/hyperplasia)
accumulation of interstitial fluid (oedema)
increased mucus secretion
epithelial damage (sensory nerve ending exposure)
sub-epithelial fibrosis

Question 13

2 types of asthma responses

Answer 13

low level TH1 reponse - initial (nonatopic individual)
strong TH1 repsonse - overtime (atopic individual)
[atopic = hyperallergic]

Question 14

low level TH1 response involves…

Answer 14

cell-mediated immune response (IgG and macrophages)

Question 15

strong TH2 response involves…

Answer 15

antibody mediated immune response (IgE)

Question 16

types of drugs used in asthma

2

Answer 16

relievers - act as bronchodilators

controllers/preventors - act as anti-inflammatory agents (reduce airway inflammation)

Question 17

examples of reliever drugs

4

Answer 17

short acting beta2-adrenoceptor agonists (SABAs)
long acting beta2-adrenoceptor agonists (LABAs)
cysLT1 receptor antagonists
methylxanthines

Question 18

examples of controllers/preventor drugs

4

Answer 18

gluccorticoids
cromoglicate
humanised monoclonal IgE antibodies
methylxanthines

Question 19

mechanism of action for beta2-adrenoceptor agonsits

Answer 19

act as physiological antagonists of all spasmogens

Question 20

short acting agents SABA

2

Answer 20

salbutamol

terbutaline

Question 21

short-acting agents result in…

Answer 21

increased mucus clearance

decreased mediator release from mast cells and monocytes

Question 22

long-acting beta2-adrenoceptor agonists

2

Answer 22

salmeterol

formoterol

Question 23

salmeratol
(LABA) is fast to act
(true/false)

Answer 23

false

saleterol is slow to act, however, formorterol is fast

Question 24

LABAs should always be coadministered with what drug?

Answer 24

glucocorticoid - steroid hormones

LABAs alone may worsen asthma by several mechanisms

Question 25

CystLT1 (cysteinyl leukotriene) receptors antagonists | 2

Answer 25

monotelukast | zafirlukast

Question 26

mechanism of action for CysLT1 receptor antagonists

Answer 26

acts competitively at CysLT1 receptor

Question 27

CysLT1 receptor antagonists prevent... | 3

Answer 27

smooth muscle contraction mucus secretion oedema

Question 28

oedema

Answer 28

swelling caused by buildup of fluid

Question 29

emphysema

Answer 29

lung disease - causes shortness of breath due to damaged alveoli

Question 30

via which route are CysLT1 receptor antagonists administered?

Answer 30

oral route

Question 31

xanthines

Answer 31

methylanthines - theophylline - aminophylline

Question 32

mechanism of action of xanthines

Answer 32

uncertain - might involve inhibition of isoforms of phosphodiesterases, inactivate cAMP and cGMP

Question 33

which drug has both anti-inflammatory and bronchodilator actions?

Answer 33

methylxanthines/xanthines | very narrow therapeutic window

Question 34

methylxanthines cause...

Answer 34

mediator release from mast cells increased mucus clearance may improved lung ventilation

Question 35

anti-inflammatory agents

Answer 35

corticosteroids - glucocortoids - mineralcocorticoids

Question 36

role of glucocorticoids | 2

Answer 36

resolves established inflammatory | prevents inflammation

Question 37

why are synthetic derivatives of cortisol, rather than cortisol itself, used in treatment of asthma

Answer 37

``` because cortisol (an endogenous steroid) possesses both glucocorticoid and minerlocorticoid actions - latter is unwanted in treatment for inflammatory conditions. [the derivatives have no mineralcorticoid activity] ```

Question 38

why is inhalational route of glucocorticoids administration is favoured in mild or moderate asthma?

Answer 38

despite not having no direct bronchodilator action glucocorticoids are delivered via inhalation to minimise adverse systemic effects

Question 39

molecular mechanism of action of glucocorticoids | 4

Answer 39

signal via nuclear receptors (GRalpha) - 1/ bind to GR alpha in cytoplasm 2/ produce dissociation of inhibitory heat shock proteins 3/ activated receptors moves to nucleus and assemble into homodimers 4/ bind to DNA altering transcription of specific genes

Question 40

cellular effects underlying the anti-inflammatory action of glucocorticoids in inflammatory cells (5)

Answer 40

eosinophil decrease (apoptosis) decreased cytokine production in Th cells mast cell decrease decreased cytokine production from macrophages dendritic cell decrease

Question 41

glucocorticoids decrease transcription of anti-inflammatory proteins and increase transcription of inflammatory proteins (true/false)

Answer 41

false | they increase anti-inflammatory protein transcription and decrease inflammatory protein transcription

Question 42

role of HDAC (histone deacetylases) and HATs (histone acetyltransferases) - produced by glucocorticoids

Answer 42

HDAC - condenses chromatin to prevent transcription | HATs - unwinds DNA, allowing transcription

Question 43

cellular effects underlying the anti-inflammatory action of glucocorticoids in inflammatory cells

Answer 43

decreased cytokines mediators in epithelial cells decreased leak in endothelial cells increased beta-2-receptors and decreased cytokines in airway smooth muscles decreased mucus secretion in mucus glands

Question 44

clinical use of glucocorticoids in asthma

Answer 44

short term use - do not alleviate early stage bronchospasms | long term use - more effective (combined with LABA)

Question 45

most common adverse effects of glucocorticoids

Answer 45

``` dysphonia -hoarse and weak voice oropharyngeal candidiasis (thrush) ```

Question 46

cromoglicate

Answer 46

delivered via inhalation (little systemic absorption) can reduce both phases of an asthma attack requires frequent dosing

Question 47

omalizumab

Answer 47

monoclonal antibodies against IgE blocks IgE expensive treatment intravenous administration