Drug control in asthma

Question 1

What is asthma?

Answer 1

Recurrent reversible obstruction of airflow in airways in response to non-noxious stimuli
Difficulty in breathing; wheezing; cough

Question 2

What are reasons in having asthma?

Answer 2

Genetically susceptibility 
Trigger also required
Allergic in >30% 
Post-viral (after infection)
Psychogenic (e.g. stress can be an asthma trigger)

Question 3

How many people are being treated for asthma in Scotland?

Answer 3

390,00

Question 4

How many deaths a day are caused by asthma in the UK?

Answer 4

5 deaths/day (2000/yr)

Question 5

What is extrinsic asthma?

Answer 5

Atopic, allergic

Question 6

What is intrinsic asthma?

Answer 6

Non-atopic, non-allergic

Question 7

What are triggers of asthma?

Answer 7

Pollen 
Dust
Animal hair
Sting
Aspirin
Cold air
Irritant chemicals
Pollutants

Question 8

What is the immune system?

Answer 8

Guards against bacteria, viruses, cancer and parasites. Normally a protective mechanisms

Question 9

What is an antigen?

Answer 9

Protein or modified protein

Question 10

How is antibody synthesis induced?

Answer 10

By monocytes (blood) macrophages, lymphocytes, mast cells- IgE

Question 11

What is the equation for the immune reaction?

Answer 11

A/g + A/b –> immune reaction

Question 12

What does cell-fixed a/b provide?

Answer 12

Recognition
Anchor
Trigger

Question 13

What chemical mediators (cytokines) are released by the cell?

Answer 13

Interleukins
Prostaglandins (PG) --> recruit other cells to the site of infection
Leukotrienes (LT)
Thromboxanes (Tx)
Histamine
Platelet activating factor )PAF)

Question 14

What are the effects of cytokine mediators?

Answer 14

Vasodilation
Pain/itch
Oedema- fluid leaks out of tissue, causes congestion
Smooth muscle contraction- contraction of bronchioles

Question 15

What is an allergy?

Answer 15

An inappropriate immune response

Form of reaction, mediators involved, vary in different tissues

Question 16

What are some effects of an allergic reaction?

Answer 16

Skin- rash, itch
Gut- vomitting
Eyes, nose- hypersecretion

Question 17

What are the stages of asthma?

Answer 17

Intermediate

Late

Question 18

What is the intermediate stage of asthma?

Answer 18

Bronchoconstriction (airways constrict), may or may not be vasodilation
Anaphylaxis leads to death

Question 19

What are the late stages of asthma?

Answer 19

Oedema–> congestion
Hyper secretion –> mucus
Inflammatory cells
Bronchoconstriction and hyperreactivity

Question 20

What does is mean if there is an increase in FEV1 in lungs?

Answer 20

Treatment is working, lungs are getting better

Question 21

What is innervation of the lungs?

Answer 21

Parasympathetic
Sympathetic
Non-adrenergic non-cholinergic (NANC)
Sensory- irritation–> reflex constriction via parasympathetic

Question 22

What are upper airways constricted by?

Answer 22

Ach via M3 receptors

Question 23

What are M3 receptors?

Answer 23

Parasympathetic nerves

Question 24

What constricts the lower airways?

Answer 24

NANC transmitters

Question 25

What relaxes the lower airways?

Answer 25

NANC transmitters (e.g. NO) and circulating adrenaline (beta 2)

Question 26

What is not in the airway muscle?

Answer 26

Sympathetic nerve supply

Question 27

What constricts blood vessel smooth muscle?

Answer 27

NA from sympathetic nerves (alpha 1)

Question 28

What relaxes blood vessel smooth muscle?

Answer 28

Circulating adrenaline (beta 2)

Question 29

What system does mucus secretion decrease?

Answer 29

Sympathetic system

Question 30

What system does mucus secretion increase?

Answer 30

Parasymathetic system, inflammatory mediators and chemical/physical stimuli

Question 31

What is the immediate phase of drug therapy?

Answer 31

Smooth muscle relaxants (treat bronchospasm)

Question 32

What is the late phase of drug therapy?

Answer 32

Steroids (treat inflammation)

Question 33

What drugs are used to treat asthma?

Answer 33

``` Beta-adrenoreceptors agonists Muscarinic antagonists Theophylline Antihistamines LT antagonists Glucocorticoids (anti-inflammatory steroids) ```

Question 34

What are beta-adrenoceptor agonists?

Answer 34

Adrenaline | Alpha + beta agonist

Question 35

What do B1 adrenoreceptors agonists affect?

Answer 35

Heart

Question 36

What do B2 adrenoreceptor agonists affect?

Answer 36

Bronchi

Question 37

What is salbutamol?

Answer 37

Beta 2 only | Inhaled aerosol or powder

Question 38

What does saltbutamol do?

Answer 38

Relaxes bronchioles Decreases secretion Increases FEV1

Question 39

What is the mechanism of saltbutamol?

Answer 39

Increases adenylate cyclase Increases cAMP Decreases Ca2+ entry

Question 40

What are examples of drugs for muscarinic antagonists?

Answer 40

Ipratropium | Tiotropium

Question 41

What does Ipratropium do?

Answer 41

N+ poor absorber Blocks bronchoconstriction due to parasympathetic reflex More useful in bronchitis

Question 42

What does Tiotropium do?

Answer 42

Prolonged (24hr) M3 selective muscarinic antagonist | Better than the older ipratropium

Question 43

What is theophylline?

Answer 43

Bronchodilator

Question 44

How does theophylline relax smooth muscle?

Answer 44

Inhibition of phosphodiesterase Increases cAMP Increases cGMP Increases release of NA and Adr

Question 45

What are some possible serious side effects of theophylline?

Answer 45

Arrythmia, convulsions, low TI

Question 46

What benefits are antihistamines?

Answer 46

Little benefit in asthma (much more in hayfever etc)

Question 47

What do antagonists of leukotrienes (LTs) do?

Answer 47

Drugs to block either the LT receptor or the synthesis of LTs E.g. montelukast

Question 48

What is an example of a useful glucocorticoid (anti-inflammatory steroids)?

Answer 48

Beclomethasone- very important as prohphylactic

Question 49

How do glucocorticoides suppress immune system?

Answer 49

Decreases lymphocyte and mass cell number Decreases reactivity Decreases mediator synthesis and release Decreases b.v. permeability

Question 50

What is the glucocorticoid mechanism?

Answer 50

``` Cytoplasmic receptor Nuclear binding RNA fro lipocortin (Annexin-1) Block PLA2 Block COX-2 ```

Question 51

What are the advantages of inhalation?

Answer 51

``` Rapid response Targetted at bronchi Need less drug Less side effects Avoid liver metabolism ```