Drugs And The Respiratory System

Front 1

What is the location of where asthma and bronchitis take place?

Back 1

The conducing zone of the bronchial tree

Front 2

What does COPD stand for?

Back 2

Chronic Obstructive Pulmonary Disease

Front 3

What are two examples of COPD?

Back 3

Emphysema

Small airways disease

Front 4

What happens when an allergic asthmatic inhales an antigen?

Back 4

Mast cells in airway sense allergen as they have IGE receptors (immunoglobulin receptors)

Mast cells release histamines when the allergen is encountered

Front 5

When mast cells release histamines in response to an allergen, what 4 things does this cause?

Back 5

Bronchoconstriction

Oedema

Mucus secretion

Inflammation

Front 6

What are the two main drugs used in the treatment of asthma?

Back 6

Bronchodilators

Anti-inflammatory agents

Front 7

What are two examples of bronchodilators?

Back 7

Beta 2-agonists

Muscarinic antagonists

Front 8

What are some examples of anti-inflammatory agents?

Back 8

Glucocorticosteroids

Xanthines

Cromones

Leukotrienes

Anti-IgE

Front 9

What is an example of a short acting beta-2 agonist?

Back 9

Salbutamol

Front 10

What is an example of a long acting beta 2 agonist?

N.B long acting means they can be taken once or twice a day

Back 10

Salmeterol

Front 11

Theophylline is a __________ used as a bronchodilator in asthma

Back 11

xanthine

Front 12

What is the mechanism of action for beta-agonists in the treatment of asthma as COPD?

Back 12

Stimulate the beta-2 receptors on lung epithelium

Increase in cAMP

Activates protein kinase A

Phosphorylates MLCK (myosin light chain kinase)

Relaxation of airway smooth muscle

Front 13

What do beta-2 adrenorecptor agonists inhibit?

Back 13

Mast cell degranulation

Front 14

How are beta-2 adrenorecptor agonists administered?

Back 14

Via the inhaled route (metered dose inhaler, dry powder, nebuliser)

N.B photo is of a nebuliser

Front 15

What are some side effects of beta-2 adrenoceptor agonists?

Back 15

Tremor

Increased heart rate

Hypokalemia (low [K+])

Front 16

Muscarinic antagonists relieve the symptoms of asthma. What do they prevent?

Back 16

Prevent smooth muscle contraction

Prevent mucus secretion induced by activation of parasympathetic nerves

Bronchoconstriction

Front 17

What are two examples of muscarinic antagonists?

Back 17

Ipratropium bromide (6hr)

Tiotropium bromide (24hr)

Front 18

What are some side effects of muscarinic antagonists?

Back 18

Dry mouth (no saliva ---> mouth ulcers ---> can't swallow)

Urinary retention

Constipation

Acute angle glaucoma

Front 19

Current anti-inflammatory therapy includes:

a) Glucocorticosteroids

b) Theophylline

c) Leuokotrirene receptor antagonists

d) Anti-IgEL Omalizumab

e) Cromones

For each of these, state how they are administered.

Back 19

a) inhaled and oral

b) oral

c) oral

d) subcutaneous

e) inhaled

Front 20

How do glucocorticosteroids work in asthma?

Back 20

Steroids are lipophilic so can pass through membrane

Steroid binds GR (glucocorticoid receptor) which is bound to a heat shock protein (HSP90)

HSP90 transfers the glucocorticosteroid in its GR receptor to the nucleus of the cell.

Once inside nucleus, HSP90 disassociates.

The complex of the steroid in its receptor affects gene expression in the nucleus

Front 21

The complex of a glucocorticosteroid in its receptors affect gene expression. Gene expression can either be enhanced or repressed. What are these terms known as?

Back 21

Trans-activation

Trans-repression

Front 22

What can glucocorticoids enhance the expression of (trans-activation)?

Back 22

Annexin

Beta-2 adrenoceptors

Mitogen kinase phosphatase

Front 23

What can glucocorticoids repress the expression of (trans-repression)?

Back 23

Cytokines

Chemokines

Adhesion molecules

Inflammatory enzymes (COX2, NOS)

Front 24

What are some actions of glucocorticosteroids in asthma?

Back 24

Inhibition of leukotriene and cytokine synthesis/release

Inhibit recruitment of inflammatory cells (T cell,s eosinophils, mast cells)

Anti-oedema

Increases beta-adrenorecptor function (enhances bronchodilator effect of beta-2 agonists)

Front 25

What does ICS stand for?

Back 25

Inhaled corticosteroids

Front 26

What are some roles of ICS in asthma therapy?

Back 26

Prevents infiltration and activation of inflammatory cells

Reduces mucosal oedema (swelling of airway wall)

Improves airflow and hence lung function

Decreases airway hyper responsiveness

Reduce symptoms (e.g bronchospasm)

Reduce frequency and severity of exacerbations

Improves quality of life

Front 27

What are some side effects of glucocorticosteroids taken by inhaled routes (e.g fluticasone propionate) ?

Back 27

Oral candidiasis ( fungal infection)

Hoarseness, cough, voice problems,

Front 28

What are some side effects of glucocorticosteroids when taken by the oral route or prolonged high dose?

Back 28

Growth retardation

Bruising

Suppression of hypothalamic pituitary axis (a complex set of direct influences and feedback interactions among : the hypothalamus, the pituitary & adrenal glands)

Osteoporosis

Hypertension

Weight gain

Ocular hypertension (pressure in eyes higher than normal)

Front 29

What are leukotriene antagonists and 5-LO inhibitors??

Back 29

Anti-inflammatory drugs that inhibit pathways to leukotriene synthesis or prevent leukotriene binding to its receptor

Front 30

5-lipoxygenase inhibitors are examples of anti-leukotriene drugs. Give an example.

Back 30

Zileuton

Front 31

Leukotriene receptor antagonists are examples of anti-leukotriene drugs. Give an example.

Back 31

Montelukast

Front 32

For each of these statements about anti-leukotriene drugs, state whether they are true or false.

1.Relativelyshort acting (need to be taken multiple times per day)

2. Greatestbenefit in mild asthma (combination with GCS)

3.Usefulfor aspirin sensitive and exercise induced asthma

4. Oralbioavailability ( the fraction of the orally administered drug that reaches the systemic circulation)

Back 32

1. False - they are relatively long acting (once per day)

2. False- greatest benefit in severe asthma

3. True

4. True

Front 33

What are some side effects of anti-leukotriene drugs? (rare)

Back 33

Headache

GI disturbance ( as blocks COX and 5-LO)

Front 34

How do xanthines work?

Back 34

Inhibit PDE

so the metabolism of cAMP is impaired

so there is more smooth muscle relaxation

Front 35

What are two examples of xanthines (2) ?

Back 35

Theophylline

Caffeine

Front 36

What is the therapeutic window for xanthines?

Back 36

Aprox 10-20 ug/mL

Front 37

What are some side effects of xanthines?

Back 37

Nausea

Vomiting

Arrhythmias

Hypokalemia ( low [K+] )

Hypotension (low bp)

Seizures

Front 38

Xanthines interact with numerous drugs which increase/decrease plasma levels. True or false.

Back 38

True

Front 39

What promotes plasma clearance of xanthines?

Back 39

Smoking

Front 40

What are cromones?

Back 40

Drugs that inhibit inflammation in a number of allergen-mediated diseases

N.B they are often found in medications for hay fever

Front 41

Complete this statement about cromones:

Cromones reduce inflammatory cell ___________ and _____________

Back 41

activation

recruitment

Front 42

What are more effective : cromones or glucocorticosteroids?

Back 42

Glucocorticosteroids

Front 43

What is an example of a cromone?

Back 43

Sodium cromoglicate

Front 44

What is omalizumab (xolair) ?

Back 44

First biological agent for treatment of asthma

Front 45

How does Omalizumab (xolair) work?

Back 45

Binds to free IgE and prevents it building up in the body

(N.B Immunoglobulin E (IgE) are antibodies produced by the immune system. If you have an allergy, your immune system overreacts to an allergen by producing antibodies called Immunoglobulin E (IgE))

Front 46

How must Omalizumab (xolair) be given?

Back 46

As a subcutaneous injection

Front 47

Omalizumab (xolair) is very costly. Therefore when is it used?

Back 47

Therefore only used in moderate to severe asthmatics whose asthma is not controlled by glucocorticosteroids

Front 48

What are immunoglobulins?

Back 48

Immunoglobulin E (IgE) are antibodies produced by the immune system.

If you have an allergy, your immune system overreacts to an allergen by producing antibodies called Immunoglobulin E (IgE). These antibodies travel to cells that release chemicals, causing an allergic reaction.