asthma

Question 1

what is asthma?

Answer 1

an condition associated with: airway hyperresponsiveness reversible airflow limitation bronchial inflammation

Question 2

what are the symptoms of asthma?

Answer 2

wheezing shortness of breath cough worse at night

Question 3

what are the triggers for asthma?

Answer 3

intrinsic- emotion, diet, cold air/ exercise

extrinsic - exposure to allergens drugs (asiprin, beta blockers), pollutants (cigerette smoke, dust, fumes)

Question 4

what are the long term aims of asthma treatment?

Answer 4

abolish symptoms maintain optimal lung function prevent permenant lung damage prevent death from acute attack avoid unnecessary side effects

Question 5

what are the differences between reliever and preventer medication for asthma?

Answer 5

reliever - bronchodilator → relax smooth muscle / widens airway (works rapidly and directly to reverse bronchoconstriction)preventer - anti-inflammatory → stops response to allergen

Question 6

name four types of bronchodilators used in asthma

Answer 6

beta 2 adrenergeric receptor agonists
theophylline
muscarinic receptor anatagonists
leukotriene receptor antagonists

Question 7

give three examples of preventer medication used in asthma

Answer 7

beclometasone sodium cromoglicate montelukast

Question 8

which target is most appropriate to treating asthma?

Answer 8

ß2 receptors as these are found in: lungs blood vessels muscle spindles

Question 9

what does salbutamol have a similar structure to?

Answer 9

adrenaline

Question 10

how can ß2 adrenergic receptor agonists be given?

Answer 10

inhaled or orally

Question 11

name two short acting ß2 adrenergic receptor agonists and explain when they would be given

Answer 11

salbutamol

terbutaline*inhaled beefore exertion to reduce exercise induced asthma - duration of action 3-5hrs

Question 12

name two long-acting ß2 adrenergic receptor agonists and explain when they would be given

Answer 12

salmeterol

formoterol* only used in patients taking inhaled steriods - can be taken 1-2 times daily - duration of actio 12hrs

Question 13

what are the side effects of ß2 adrenergic receptor agonists? explain why these occur

Answer 13

tremor - ß2 receptors in muscles activated increased HR - stimulation of cells in SA node reduced K+ (hypokalaemia) - stimulation of sodium/potassium pump nervous tension/ headache - activation of ß2 receptors in CNS

Question 14

how can the systemic effects of ß2 adrenergic receptor agonists be reduced?

Answer 14

by inhaling drug

Question 15

when would a glucocorticosteroid be used in asthma?

Answer 15

as a preventer

Question 16

name five glucovorticosteroids that are used via an inhaler to prevent asthma attacks

Answer 16

beclomethasone diproprionate
budesonside
fluticasone propionate
prednisolone
hydrocortisone

Question 17

why are the systemic effects of inhaled glucocorticosteroids reduced?

Answer 17

poor bioavailablity

Question 18

what can glucocorticosteroids often be administered in combination with?

Answer 18

ß2 adrenergic receptor agonists

Question 19

describe the activation of ß2 adrenoceptors

Answer 19

ß2 adrenergic receptor agonists bind to ß2 receptor causing a conformational change to the molecule. This change in shape converts ATP to cAMP which activates PKA and muscle relaxation

Question 20

describe the actions of glucocorticoids in asthma

Answer 20

reduces production of:
cytokines, spasmogens (LTC4, LTD4), leuocyte chemotaxins (LTB4, PAF)
therefore reduces:
bronchospasm, recruitment and activation of inflammatory cells

Question 21

explain the mechanism of action of glucocorticosteroids (GCs)

Answer 21

GCs are synthesised from cholesterol allowing them to cross cell membrane
when inside the cell GCs bind to steroid receptors
the drug-receptor complex forms a dimer which can cross into nucleus
in nucleus the dimer binds to specific DNA sequence inducing or supressing genes
protein production influenced
GCs inhibit transcription of COX-2 gene - reducing protein production and inflammation

Question 22

what are the side effects of glucocorticosteroids?

Answer 22

local immunosuppression - oral thrush local effects on vocal cords - dysphonia (hoarseness)

Question 23

what is prednisolone used forn and how does it work?

Answer 23

treats acute asthma attack short course - 7 days (high dose) continue with high dose inhaled steroid in chronic/severe asthma
works by: suppressing immune system activity and release of inflammatory mediators

Question 24

explain the danger of stopping glucocorticosteroids abruptly

Answer 24

results in acute adrenal insuffiency as patients ability to synthesise GCs has been suppressed → leads to patient being unable to maintain a stress response leading to addisonian crisis

Question 25

what are antimuscarinic receptor antagonists and what are they used for?

Answer 25

``` short acting (reliever) - 3-5hrs used alonside high-dose inhaled glucocorticosteroids for severe asthma ```

Question 26

what is the mechanism of action for antimuscarinic receptor antagonists?

Answer 26

block muscarinic receptors → blocks action of endogenous acetylcholine inhibits elevated mucus secretion

Question 27

given an example of an antimuscarinic receptor antagonists and explain its side effects

Answer 27

ipratropium - causes dry mouth and precipitates glaucoma

Question 28

what are cromoglicates and how do they work?

Answer 28

cromones inhibit release of chemicals from inflammatory cells (mast cells) → prevents bronchospasm reduces allergen induced responses and bronchospasm during/after exercise stops mast cell degranulation   

Question 29

name 2 cromoglicates

Answer 29

nedocromil sodium sodium cromoglicate | * stops mass cells releasing histamine and other chemicals - mainly used in children

Question 30

what do leukotrienes cause?

Answer 30

bronchoconstriction release of inflammatory cells increase in secretions in airways

Question 31

what do leukotriene receptors antagonists do?

Answer 31

relax airways and prevent inflammation

Question 32

give two examples of leukotriene receptor antagonists and explain side effects

Answer 32

montelukast zafirlukast* causes GI disturbance

Question 33

when is theophylline (aminophylline) used?

Answer 33

orally or IV in patients with persistant symptoms / severe acute asthma

Question 34

can theophylline be used with other drugs?

Answer 34

yes - ß agonists and/or steroids

Question 35

what are the drawbacks and side effects of theophylline?

Answer 35

drawbacks: narrow therapetic windowside effects: increased HR, palpitations, convulsions, headache

Question 36

explain the mechanism of action of theophylline

Answer 36

blocks phosphodiesterase enzyme (PDE) which breaksdown into 5'AMP - therefore more cAMP is available to stimulate smooth muscle relaxation

Question 37

what is omalizumab (xolair) used for and how it given?

Answer 37

an antibody (given subcutaneously) every 2-4 weeks reduces effect of allergen induced reactions used in adults with severe allergic asthma not controlled by ß agonists and glucocorticosteroids

Question 38

what are the side effects of omalizumab?

Answer 38

bruising pain on injection small risk of anaphylaxis

Question 39

what is the mechanism of action of omalizumab?

Answer 39

antibody inhibits binding of IgE to receptor surface of mast cell and basophils prevents release of pro-inflammatory mediators and reduces allergen induced airway reactions

Question 40

describe the treatment strategy for asthma from mild to severe

Answer 40

inhaled short acting ß2 agonists (as needed) inhaled steroids add inhaled long acting ß2 agonists and increase dose of inhaled steroids short and long acting ß2 agonists and inhaled steroids and another drug (eg. LTR antagonist) continuous or frequent use of oral steriods (and immunosuppressants

Question 41

what can be substituted for inhaled ß2 agonists in stage 1 of the asthma treatment strategy?

Answer 41

ipratropium oral ß agonists theophyllines

Question 42

describe what therapy would be given in acute asthma attack

Answer 42

bronchodilators given via nebuliser glucocorticosteroids given (oral prednislone, IV hydrocortisone) - route depends on severity oxygen therapy needed if O2 saturation reduced ( in poor response aminophylline injection (severe, acute attacks)

Question 43

what are the side effects of cromoglicates?

Answer 43

irritation of upper resp. tract | hypersensitivity reactions

Question 44

what are the actions of leukotriene antagonists?

Answer 44

act on cystrinyl-leukotriene receptors | prevent actions of LTC4, LTD4 (which are brochial spasmogens and stimulate mucus secretion)

Question 45

what are the side effects of leukotriene antagonists?

Answer 45

headache | GI disturbance

Question 46

when would antimuscarinic receptor antagonists be used?

Answer 46

in asthma where there is evidence of overactive Ach production

Question 47

describe the muscarinic system in normal airways and in some asthma airways

Answer 47

normal - Ach released from cholinergic nerves, few muscarinic receptors activated , smooth muscle relaxed airways open asthma - Ach more active so more muscarinic receptors activated which causes contraction of smooth muscle