L13 Respiratory Pharmocology

Question 1

Asthma

Answer 1

Chronic, intermittent and reversible airway disease causing obstruction and type 4 hypersensitivity to small airways

Question 2

Features of asthma

Answer 2

Eosinophilic 
Mucosal oedema and plugging 
Bronchospasm - constriction of small airways 
Wheezing 
Coughing 
Atopy

Question 3

Considerations before stepping up or down

Answer 3

Adherence
Inhaler technique
Eliminate triggers I.e. allergens

Question 4

Uncontrolled asthma

Answer 4

3+ days a week with symptoms
3+ days a week with SABA required
1+ nights a week with awakening due to asthma

Question 5

Stepwise treatment of asthma

Answer 5

1. SABA throughout - salbutamol
2. low dose ICS
3. Regular preventer - low dose ICS
4. Add LABA - salmeterol
5. Increased dose of ICS or LTRA
6. Specialist therapies

Question 6

Inhaled corticosteroid examples

Answer 6

Beclometasone
Budesonide
Fluticasone

Question 7

ICS mechanism of action

Answer 7

Regular preventer when reliever alone is not sufficient

• passes through the plasma membrane as liopophilic
• activates cytoplasmic receptors (glucocorticoid receptor in cytosol)
• forms complex and passes into the nucleus
• modifies transcription therefore controls gene expression

Question 8

Effects of ICS

Answer 8

Reduces mucosal inflammation - activates genes for anti- inflammatory mediators and represses genes for inflammatory mediators
Widens airways - activates genes for Beta 2 agonists for bronchodilation
Reduces mucus - represses genes for inflammatory mediators

• Therefore reduces symptoms and exacerbations to prevent death

Question 9

Side effects of ICS

Answer 9

Local immunosuppression - candidiasis (oral thrush) and hoarse voice

Pneumonia risk in COPD patients

Question 10

Pharmacokinetics of ICS

Answer 10

• Poor oral bioavailability but inhaled
• large lipophilic side chain for slow dissolution in aqueous bronchial fluid
• adheres and acts locally
• high affinity for glucocorticoid receptors in the cytosol

Question 11

If ICS taken orally

Answer 11

• Transported from stomach to the liver via the hepatic portal system quickly
• almost complete first pass metabolism - low risk of systemic side effects

Question 12

Beta 2 agonists

Answer 12

SABA - short acting beta 2 agonist used when required - symptom relief via bronchodilation

LABA - add on to ICS used when required

• bronchodilation
• increases mucus clearance by cilia action
• prevents bronchoconstriction prior to exercise

Question 13

Beta 2 agonists used regularly

Answer 13

Reduced tolerance

Quickly fixed in young adults

Question 14

Beta 2 agonist examples

Answer 14

Fast:
SABA - salbutamol and terbutaline
LABA - formoterol (more potent and efficacious than salmeterol)

Slow:
LABA: salmeterol

Question 15

Beta 2 agonist mechanism

Answer 15

1. Beta 2 agonist bind to GPCR
2. GDP is replaced by GTP
3. G alpha S sub unit dissociates from the G beta and gamma sub unit
4. G alpha S activates adenyl cyclase
5. Which stimulates ATP to convert into cAMP
6. cAMP activate protein kinase A
7. Which causes bronchial smooth muscle relaxation

Question 16

Beta 2 agonist ADR

Answer 16

Increases sympathetic activity - flight or flight effects e.g.

• tachycardia
• palpitations
• anxiety
• tremor

COPD patients:

• Supraventricular tachycardia - increased SAN activity, increases HR and decreased refractory period and the AVN
• increased risk of right sided HF And CVD

Increased glycogenolysis (liver) - increased blood glucose 
Increased renin (kidney) - due to increeas3d HR

Question 17

Why is LABA used with ICS?

Answer 17

Increased risk of death when used alone

Masks airway inflammation and near fatal attacks

Question 18

Contraindications of beta agonists

Answer 18

Beta blockers as antagonist

Question 19

When is LABA added?

Answer 19

Asthma not controlled with ICS

Frequent asthma exacerbations

Question 20

Advantages of combined inhaler

Answer 20

Increase adherence
Safer for the patient - as not taking LABA alone
Less prescriptions
Easier to take

Question 21

Leukotriene receptor antagonist example

Answer 21

Montelukast

Question 22

Leukotrienes

Answer 22

• Mast cells and eosinophils release LTC4
• leukotrienes which cause bronchoconstriction, increased mucus production and mucosal oedema as there is increased vascular permeability
• via CysLT1 - GPCR

Question 23

LTRA mechanism of action

Answer 23

Block CysLT1 receptors preventing bronchoconstriction, increased mucous production and mucosal oedema

Only useful in 15% of asthmatic patients

Question 24

ADRs of LTRA

Answer 24

Headache
GI disturbances
Dry mouth
Hyperactivity

Question 25

Additional controller therapies

Answer 25

LAMA - long acting muscarinic antagonist - tiotropium SAMA - short a timing muscarinic antagonist- ipratropium Adenosine receptor antagonist - theophylline Special maintenance therapy - prednisolone

Question 26

LAMA mechanism of action

Answer 26

Use: - in severe asthma and COPD Mechanism: - selective for M3 - inhibition of muscarinic receptors - anticholinergic - prevents bronchoconstriction

Question 27

Side effects of LAMA

Answer 27

Anticholinergic therefore: - dry mouth - urinary retention - dry eyes

Question 28

Adenosine receptor antagonist

Answer 28

Type of methylxanthine - found in coffee Also acts as a phosphodiesterase inhibitor Theophylline - oral Aminophylline - IV in acute emergency asthma patients

Question 29

ADRs of adenosine receptor antagonists

Answer 29

Narrow therapeutic index Potentially life threatening arrhythmia Interactions with CYP450 inhibitors - increases the concentration of theophylline as there is less metabolism

Question 30

Prednisolone

Answer 30

Oral steroid for severe uncontrolled asthma Prescribed by a specialist and given a steroid card (COPD) Post acute exacerbation - short course for at least 5 days Post acute COPD - 5-7 days after hospital discharge

Question 31

Self management plan

Answer 31

For asthmatic patients | Written instruction of when and how to take inhalers

Question 32

Acute severe asthma presentation

Answer 32

Struggling to complete sentences Resp rate - 25 + Heart rate - 110+ Peak flow - a third to half of best or predicted

Question 33

Life threatening

Answer 33

Peak flow - less than a third of best or predicted Arterial oxygen saturation - less than 92% Silent chest Cyanosis Exhaustion Hypotension Altered conscious level

Question 34

Treatment for acute severe or life threatening asthma

Answer 34

Oxygen - aim for 94-98% High dose nebulised beta 2 agonist Prednisolone for 7- 14 weeks along with ICS Nebulised ipratropium bromide with B2 agonist - if beta 2 agonist response is poor Aminophylline is life threatening with no success with other treatments - caution if taking theophylline

Question 35

COPD 5 tasks of management

Answer 35

``` Task 1 - confirm COPD diagnosis Task 2 - stop smoking Task 3 - record MRC dyspnoea score - pulmonary rehabilitation for score less than 2 Task 4 - offer vaccinations Task 5 - consider medication ```

Question 36

How to treat COPD

Answer 36

Acute exacerbation requiring hospitalisation: - nebulised salbutamol or ipratropium driven by air not oxygen if hypercapnic - prednisolone (less effective than eosinophilic asthma as COPD is neutrophilic) - antibiotics - review of chronic treatment and action plan

Question 37

Inhalers

Answer 37

Blue - salbutamol reliever SABA Brown - beclometasone preventer - ICS Green - Ipratropium - SAMA

Question 38

Inhaler options

Answer 38

Pressurised metered dose inhalers - slow breath in and hold - can be used with spacer Breath actuated pMDI - when breathing in Dry powder inhalers (DPI) - fast deep inhalation

Question 39

Particle size

Answer 39

1-5 microns - perfect Too small - inhaled to alveoli and exhaled without being deposited Too big - deposited in mouth and oropharynx