CPT18 - Respiratory Pharmacology

Question 1

NICE guidelines for management of asthma

Assessment and Signs of Uncontrolled Asthma

Regular Preventer
Initial Add-On
Additional Control

Answer 1

1.) Assessment - symptoms, lung function, optimise inhaler technique and adherence, eliminate triggers

2. ) Scaling the Algorithm - uncontrolled asthma:
   - using SABA or experiencing symptoms > 2x a week
   - waking up at night due to asthma at least once a week
3. ) Regular Preventer - low dose ICS + SABA prn
   - ICS is a daily dose whilst the SABA is prn
4. ) Initial Add-On - low dose ICS + SABA + LTRA/LABA
   - LTRA instead of a LABA simply because its cheaper
   - if LTRA is ineffective, switch to more expensive LABA
5. ) Additional Control - increasing dose of ICS
   - increasing ICS to a medium dose

Question 2

4 features of using inhaled corticosteroids (ICS) to manage asthma

Examples x3
Mechanism x3
Pharmacokinetics x3
Side Effects x3

Answer 2

1.) Examples - beclomethasone (Qvar), budesonide, fluticasone

2. ) Mechanism - modifies gene transcription (steroid)
   - activation: ß2 receptors, anti-inflammatory mediators
   - repression: inflammatory mediators (e.g. cytokines)
   - ↓mucosal inflammation, ↓mucus, widens airways
3. ) Pharmacokinetics
   - low oral bioavailability and lipophilic side chain added
   - slow dissolution in aq bronchial fluid so works there
   - high affinity for glucocorticoid receptor
4. ) Side Effects - local immunosuppressive action:
   - oral candidiasis, hoarse voice, cough, pneumonia (in COPD)

Question 3

4 features of using ß2-agonists to manage asthma

Examples x4
Mechanism
Usage
Side Effects x5

Answer 3

1. ) Examples-short or long (12h) acting, fast or slow onset
   - SABA: salbutamol, terbutaline
   - LABA: salmetrol (slow), formoterol (fast),
2. ) Mechanism - bronchodilation in airway SM
   - also ↑mucus clearance by action of cilia
   - ß-blockers can reduce effects of ß2-agonists
3. ) Usage - SABA is used as required, LABA is B.D
   - prior to exercise to prevent bronchoconstriction
   - Fostair inhaler contains combo of ICS + LABA
4. ) Side Effects
   - ↑SNS: tachycardia, palpitations, anxiety, tremor
   - SVTs: ↑HR leads to ↓refractory period at the AVN
   - ↑glycogenolysis (liver), ↑renin (kidneys)
   - muscle cramps (LABA)

Question 4

3 features of using a leukotriene receptor antagonist (LTRA) to manage asthma

Example
Mechanism
Side Effects x4

Answer 4

1.) Example - montelukast (oral)

2. ) Mechanism - blocks CysLT1 receptor
   - LTC4 is released by eosinophils/mast cells and binds to CysLT1-R to: ↑bronchoconstriction, ↑mucus and ↑oedema
3. ) Side Effects
   - headache, dry mouth, GI disturbance, hyperactivity

Question 5

4 other drugs used to manage severe asthma

Tiotropium
Ipratropium
Theophylline/Aminophylline
Non-Inhaled Corticosteroids

Answer 5

1. ) Tiotropium-long acting muscarinic antagonist (LAMA)
   - relative selectivity for M3 (↓bronchoconstriction)
   - side effects: anticholinergic effects (e.g. dry mouth)
2. ) Ipratropium - short acting MA (SAMA)
   - less selectivity for M3 receptors than the LAMA
   - nebulised w/ oxygen so ↓systemic side effects
   - main side effect is a dry mouth (nebuliser)
3. ) Theophylline - adenosine receptor antagonist
   - inhibits TNF-alpha and ↓leukotriene synthesis
   - narrow therapeutic index, can cause arrhythmias
   - concentrations increase w/ CYP450 inhibitor
   - aminophylline is the IV (soluble) form
4. ) Non-Inhaled Corticosteroids - specialist maintenance
   - oral prednisolone or IV hydrocortisone (acute)
   - post acute exacerbation for at least 5 days

Question 6

Management of Acute Severe/Life Threatening Asthma

OH S(H)IT

Answer 6

1.) Oxygen - aim for 94-98% SATS

2. ) Hydrocortisone (IV) - steroids
   - IV > oral prednisolone due to faster action
   - starting early reduces mortality and readmission

3.) SABA - nebulised salbutamol

4. ) Ipratropium Bromide - nebulised
   - used if SABA has poor response alone
5. ) Theophylline - oral
   - IV aminophylline if life-threatening w/ no improvement

Question 7

Management of acute exacerbations of COPD

Answer 7

1. ) Salbutamol +/- Ipratropium
   - nebulised w/ air if patient is hypercapnic
2. ) Corticosteroids - oral prednisolone 40mg (5 days)
   - can be less effective in eosinophilic asthma due to reduced action on neutrophils

3.) Antibiotics - broad sprectrum if severe

Question 8

3 types of inhalers

pMDI
Breath-Acuated pMDI
DPI

Answer 8

1. ) Pressurised Metered Dose Inhalers (pMDI) - classic
   - inhale and press at the same time
   - can be used w/ a spacer to improve delivery
2. ) Breath-Actuated pMDI
   - automatic release upon inspiration
3. ) Dry Powder Inhalers (DPI)
   - micro-ionised drug plus carrier powder