Respiratory pharmacology

Question 1

Lung related disease is the biggest cause of death in the UK. Is lung related mortality increasing or decreasing?

Answer 1

Increasing due to an ageing population

Question 2

What is the biggest cause of respiratory death?

Answer 2

Lung cancer

Question 3

What are the top 2 selling respiratory drugs?

Answer 3

Inhaled corticosteroids

Bronchodilators

Question 4

If a drug ends in -sone or -lone, what type of drug is it likely to be?

Answer 4

Corticosteroid

Question 5

If a drug ends in -mab, what type of drug is it likely to be?

Answer 5

Monoclonal antibody

Question 6

In the respiratory tract, does the conducting or respiratory region of the lung have the higher surface area?

Answer 6

Respiratory region (95% of lungs surface area) - this means that a lot of the drug will be absorbed here

Question 7

Do smaller or larger particles get to the alveolar region of the lung best?

Answer 7

Smaller particles

Larger particles get to the upper airways, mouth and throat best.

Question 8

Which area in the lung has the fastest absorption?

• respiratory region
• intermediate region
• main bronchi

Answer 8

respiratory region in the alveoli

Question 9

what is a drawback of intranasal administration?

Answer 9

anatomical limitation (narrow lumen)

Question 10

if a patient inhales too forcefully, where is the drug likely to be deposited?

Answer 10

in the upper airways, mouth and throat

Question 11

name 4 different delivery systems for inhaled drugs

Answer 11

1. pressurised metered dose inhalers - fine spray when pressing down
2. spacer devices - slows down particles and allows more time for evaporation of propellant so drug can be inhaled
3. dry powder inhalers - no propellant, needs sufficient inspiratory effort to breathe in
4. nebulisers - disperinqs a liquid into a fine mist which can be inhaled through mask or mouthpiece. No co-ordination needed.

Question 12

Benefits of inhaled drugs? (8)

Answer 12

• Lungs are robust and are able to safely handle repeated exposure to therapeutics
• Large surface area
• Rapid absorption
• Action is either directly on the lung or enters the systemic circulation
• Lungs are naturally permeable to peptides
• Fewer drug metabolising enzymes in the lung compared to blood or liver
• Non-invasive port of entry into systemic circulation
• Fewer systemic side effects

Question 13

Describe how cell signalling causes bronchoconstriction to occur

Answer 13

Voltage gated calcium channels or histamine causes cell signalling which activates ROCK (kinase in cell) which phosphorylates actin and myosin causing muscles to contract and leads to bronchoconstriction.

Question 14

What are the 2 categories of bronchodilators?

Answer 14

1. adrenergic (sympathetic) to cause bronchodilation

2. Anti-cholinergic (parasympathetic) to block bronchoconstriction from happening

Question 15

how do b2 adrenoceptor antagonists work?

Answer 15

they work on b2 adrenoceptors to cause smooth muscle relaxation and bronchodilation and inhibit histamine release from mast cells

Question 16

give an example of a B2 adrenoceptor antagonist

Answer 16

SABA - salbutamol
LABA - formoterol or salmeterol
Ultra LABA - indacaterol allows once daily dosing

Question 17

How do anticholinergics work? Give an example of a drug

Answer 17

they work ACh being to muscarinic receptors which prevents smooth muscle contraction in the airways.
Example: atropine, ipratropium bromide, tiotropium bromide.

Question 18

What drug class can be used as anti-inflammatory for asthma

Answer 18

glucocorticoids (corticosteroids)

Question 19

Name some ICS used in the UK

Answer 19

beclomethasone dipropionate
budesenide
ciclesonide
fluticasone proprionate
mometasone furoate

Question 20

how do corticosteroids work to reduce inflammation?

Answer 20

• They reduce the number of inflammatory cells in the airways
• Suppress the production of chemotactic mediators.
• Inhibit inflammatory cell survival in the airways (premature apoptosis)
• Suppress inflammatory cell expression in airway epithelial cells

Question 21

Side effects of ICS?

Answer 21

use the lowest dose possible

• loss of bone density
• adrenal suppression
• cataracts, glaucoma

Question 22

some asthmatics can become resistant to corticosteroids, with 1% requiring oral corticosteroids. Resistance is often linked to what type of asthma?

Answer 22

Non-eosinophilic (neutrophilic asthma)

Question 23

Do corticosteroids work for COPD?

Answer 23

No, most patients are resistant, responsive patients are thought to have concomitant asthma.

Question 24

What effect do B2 agonists and ICS have when given together?

Answer 24

They help each other work

• glucocorticoids increase expression of cell surface receptors helping beta agonists to work
• LABAs increase the translocation of ICS from cytoplasm into the nucleus helping them work.

Question 25

Bronchiectasis occurs when there is excessive and chronic persistent inflammation in the lung. Antibiotics can be used to treat infective organisms but what remains the main treatment for severe disease?

Answer 25

Surgery and transplantation

Question 26

Idiopathic pulmonary fibrosis occurs when there is excessive fibrous connective tissue leading to permanent scarring, airway wall thickening and breathing difficulties. What is the treatment for this condition?

Answer 26

Transplants are best option for severe cases
Pirfenidone (reduces fibroblast proliferation and collagen production) and nintendanib (slows progression of fibrosis in the lung) are new drugs which significantly slow down the rate of disease progression in IPF.