Asthma and COPD

Question 1

Define asthma

Answer 1

Reversible increases in airway resistance, involving bronchoconstriction and inflammation. FEV1:FVC is less than 70-80% - shows airway resistance. Variations in PEF which improves w beta2 agonist (morning dipping). Managed pharmacology but poor compliance = failure

Question 2

What is COPD

Answer 2

Chronic bronchitis + emphysema.
>90% smoking related
FEV1 reduces
Little variation in PEF, little reversibility w beta 2 agonist

Question 3

How does the parasympathetic nervous system control bronchial calibre?

Answer 3

ACh acts on M3 receptors
Bronchoconstriction
Increase mucus

Question 4

How does the sympathetic nervous system control bronchial calibre?

Answer 4

Vagus nerves stimulates airways.
Circulating adrenaline acting on beta2-adrenoceptors on smooth muscle causing relaxation and inhibiting mucus secretion
Releasing NA acting on adrenoceptors on parasympathetic ganglia to inhibit transmission

Question 5

What can provoke an asthma attack?

Answer 5

Genetic predisposition is provoked by allergens, cold air, viral infections, smoking, exercise. Characterised by EARLY and LATE phase

Question 6

List the clinical features of an asthma attack

Answer 6

Wheezing
Breathlessness
Tight chest
Cough - worse at night/exercise
Decreases in FEV1, reversed by beta2 agonist

Question 7

Describe the mechanism for asthma after a stimulus

Answer 7

–> Causes mast cells in lungs to become unstable to release mediators: spasmogens (–>bronchospasm) and chemotaxins (–>WBCs to arrive and inflammation)

Question 8

TRUE or FALSE? Early phase shows a recovery in an asthma attack and then minutes later a late phase shows much smaller response

Answer 8

False! Late phase comes hours later and is much more prominent response

Question 9

List examples of spasmogens

Answer 9

Histamine
Prostaglandin (bronchoconstrictors))
Leukotrienes (bronchoconstrictors and chemotaxins)
Platelet activating factor

Question 10

After arachidonic acid is chopped out of membranes by phospholipase A2 enzyme they produce what two mediators and by what pathway?

Answer 10

Prostaglandin through cyclooxygenase enzyme (COX pathway) and leukotrienes through lipoxygenase enzyme (LOX pathway)

Question 11

How do bronchodilators work?

Answer 11

Reverse bronchospasm (early phase). Rapid relief - RELIEVERS (before an attack)

Question 12

What are preventers?

Answer 12

Taken continuously, used to prevent an attack

Prevents but no relief

Question 13

What is the 1st choice reliever for asthma patients and what is the mechanism?

Answer 13

BETA2-ADRENOCEPTOR AGONISTS (salbutamol). Increases FEV1. Acts on beta2 adrenoceptors in smooth muscle which is coupled w adenylyl cyclase to increase cAMP -> relaxation.

Question 14

Why is a non-selective (affecting beta1&2) agonist no longer 1st choice reliever?

Answer 14

Had an affect on the heart due to beta-1 receptors on the heart

Question 15

Why are beta2 agonists given by inhalation

Answer 15

To reduce side effects

Question 16

What happens with prolonged use of beta2 agonists and what is given to patients to reduce this?

Answer 16

Receptor down-regulation - it will become less responses. Given steroid to reduce this

Question 17

When are long acting beta agonists (e.g. salmeterol) given and why?

Answer 17

For long term prevention and control (overnight). Binds to receptor and is retained. Has to use with steroids and associated w incr mortality. It isn’t a reliever

Question 18

What are Xanthines?

Answer 18

Bronchodilators - 2nd line use. Oral. Phosphodiesterase inhibitors (enzymes that break down cAMP)

Question 19

How do M-receptor antagonists work and how/when are they used?

Answer 19

Block parasympathetic bronchoconstriction (specific for M3).
Inhalation - to reduce muscarinic side effects (dry mouth, constipation)
Little use in asthma, used in COPD

Question 20

Anti-inflammatory agents - CORTICOSTEROIDS are preventative, what is their mechanism and what are they mainly used for?

Answer 20

(e.g. beclomethasone - inhalation, or prednisolone - oral)
Effects the AA pathway - activate intracellular receptors leading to gene transcription (decr cytokine production) and production of LIPOCORTIN -(inhibits synthesis of PGs and LTs. They are more focused on the anti-inflammatory response

Question 21

Give the side effects of giving steroids with beta2 agonists and say how you can reduce these

Answer 21

Throat infections (thrush), hoarseness - reduce this by washing mouth out after use or use a space device.
Adrenal suppression - it will produce less natural steroids - improve by limiting time scale of use.

Question 22

They block leukotrienes. They are preventative and bronchodilators. They antagonise actions of LTs. They are a good choice for atopic patients bc it helps with the anti-inflammatory response - what am I?

Answer 22

Leukotriene receptor antagonists (LTRAs)

Question 23

Omalizumab - for difficult to treat asthma as a last choice drug - what is it and how does it work?

Answer 23

MAB - monoclonal antibody. Directed against IgE but not bound. Prevents them from binding to immune cells and which leads allergen-induced mediator release in allergic asthma.

Question 24

What is the stepped care approach in BTS guidelines for asthma?

Answer 24

Short acting beta2 agonist plus steroid.
+trial of LABA or LTRA or xanthine.
+increase dose of inhaled steroid.
+oral steroid.

Question 25

What is considered a failure of treatment in asthma according to BTS guidelines?

Answer 25

Identified as attacks or is they need to use salbutamol for relief more than twice a week

Question 26

When are spacer devices given?

Answer 26

For young and old patients
Patients w poor technique
To reduce steroid impaction

Question 27

How are bronchodilators, inhaled steroid, antibiotics and oxygen therapy used in COPD

Answer 27

Bronchodilators - beta2-agonist +tiotropium (longer acting M antagonist)
Inhaled steroids are less effective in COPD.
Antibiotics are used for infections as lungs are susceptible

Question 28

Describe (roughly) the summary of guidelines to manage COPD

Answer 28

Look at yellow diagram in presentation by randall

Question 29

Why are NSAIDs (aspirin, ibuprofen) not used in patients w asthma

Answer 29

They may provoke asthma by increasing LT production. They are COX inhibitors - means more AA goes down the LOX pathway - more leukotrienes for an asthma attack.

Question 30

Why are beta-blockers contraindicated in asthma patients.

Answer 30

Act upon adrenoceptors in the heart (for heart failure) but can still affect the lungs (even if it is selective) - therefore can induce an attack as it blocks the effect of a drug (salbutamol) and natural adrenaline to produce cAMP.
(note: they are used in caution w COPD - you need to weigh consequences).