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Respiratory > Pharmacological Management of Asthma and COPD > Flashcards

Pharmacological Management of Asthma and COPD Flashcards

1
Q

Describe the characteristics and pathogenesis of asthma.

A
  • Characteristics:
    • Airway narrowing which is reversible
    • Airway hyper-responsiveness
    • Airway inflammation
  • Pathogenesis:
    • Acute and chronic inflammatory responses in airways
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2
Q

Describe the cross-section of a bronchiole in severe chronic asthma.

A
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3
Q

What are the ideal outcomes of asthma control?

A
  • No daytime symptoms.
  • No night-time waking due to asthma.
  • No need for rescue medication.
  • No asthma attacks.
  • No limitations on activity including exercise.
  • Normal lung function (FEV1 and / or PEF > 80% predicted or best).
  • Minimal side-effects from mediation
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4
Q

What are the routes of administration of asthma treatment?

A
  • Primarily - inhalation of aerosol or dry powder.
    • Rapid, reduced systemic side-effects
    • Particle size is important
  • Oral
  • Injectable
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5
Q

What are the 2 major groups of drugs for asthma managemet?

A
  • Bronchodilator (relievers)
  • Anti-inflammatory agents (preventers)
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6
Q

What are the different types of inhaler used in asthma management?

A
  • MDI = metered dose inhaler.
  • Breath-actuated (e.g. autohaler, easibreathe).
  • Accuhaler - dry powder.
  • Via a spacer / aerochamber.
  • Prescribe by brand (except salbutamol).
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7
Q

Describe the principle of using a spacer.

A
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8
Q

What are the 5 categories of drugs used to treat and prevent asthma? Give an example of each.

A
  • β2-adrenoceptor agonists
    • Short-acting (SABA) e.g. salbutamol
    • Long-acting (LABA) e.g. salmeterol
  • Glucocorticoids
    • E.g. beclometasone, budesonide
  • Cysteinyl leukotriene antagonists (LTRA)
    • Montelukast
  • Methylxanthines
    • Theophylline and derivatives
  • Monoclonal antibodies - Anti-IgE treatment
    • Omalizumab
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9
Q

Describe the SIGN guidelines on asthma management (treatment ladder - 5 steps).

A
  • It is important to remember that you are not only going in one direction.
  • As well as stepping up the treatment ladder, you can also step down, especially in children.
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10
Q

Describe the mechanism of action of β2-adrenoceptor agonists.

A
  • Stimulates bronchial smooth muscle β2 receptors, relaxes muscles, dilates airways, reducing breathlessness.
  • Inhibit mediator release from mast cells and infiltrating leucocytes.
  • Increase ciliary action of airway epithelial cells - aids mucus clearance.
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11
Q

What are the side-effects of β2-adrenoceptor agonists if given orally / I.V. or high dose inhaled?

A
  • Sympathomimetic effects
  • Muscle pain / cramps
  • Electrolyte disturbances (e.g. hypokalaemia)
  • Hyperglycaemia
  • Paradoxical bronchospasm (very rare)
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12
Q

Describe SABAs.

A
  • Short-acting β2 agonist
    • Salbutamol
    • Terbutaline
  • Fast-acting, lasts up to 5 hours.
  • ‘Rescue remedy’ / ‘reliever’
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13
Q

Describe LABAs.

A
  • Long-acting β2 agonist
    • Salmeterol
    • Formoterol
  • Lasts longer (up to 12 hours).
  • Given to prevent bronchospasm (at night or during exercise) in patients requiring long-term therapy.
  • Salmeterol is slower to act than formoterol.
  • Do not prescribe as sole therapy for asthma - add a preventer, use as combination inhaler.
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14
Q

What is the alternative to a β2 agonist which will also have a bronchodilatory effect?

Give examples.

A
  • Muscarinic receptor antagonists.
    • Ipratropium (SAMA)
    • Umeclidinium (LAMA)
  • Very seldom used - in severe asthma already on β2 agonists and steroids.
  • Muscarinic antagonist has the same effect as β2 agonist.
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15
Q

What is the mechanism of action of ICS?

A
  • Glucocorticoids
  • Anti-inflammatory and immunosuppressive.
  • Inhibit formation of cytokines (includes interleukins).
  • Inhibit activation and recruitment to airways of inflammatory cells.
  • Inhibit generation of inflammatory prostaglandins and leukotrienes, thus reducing mucosal oedema.
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16
Q

Under what circumstances would glucocorticoids be prescribed?

A
  • “Preventers”.
  • Used at step 2 in the treatment ladder.
  • Used if:
    • Patient has had an asthma attack in the last 2 years.
    • Patient has symptoms or using SABA more than 3 times per week.
    • Patient is waking at night with wheeze.
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17
Q

Describe the action of glucocorticoids on T-lymphocytes in allergic asthma.

A
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18
Q

Describe the anti-inflammatory effects of inhaled corticosteroids.

A
  • Adherence is vital to see effects.
  • Slower onset of action.
  • Decreases mucosal inflammation, widens airways and reduced mucous secretion.
  • Longer term effects over months - reduction in airway responsiveness to allergens and irritants (including exercise).
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19
Q

Give examples of ICS.

What are their routes of administration and side-effects?

A
  • Usual route = inhaled.
    • Beclomethasone
    • Budesonide
    • Fluticasone
  • Route of administration in acute severe attacks = oral or IV.
    • Oral = Prednisolone
    • I.V. = Hydrocortisone
  • Side effects:
    • Oropharyngeal candidiasis
    • Dysphonia (hoarseness)
  • Systemic side effects (chronic high dose, inhaled and oral)
    • Osteoporosis
    • Adrenal insufficiency
    • Growth retardation
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20
Q

What are leukotriene receptor antagonists used for?

“The Lukasts”

A

For asthma prophylaxis​

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21
Q

What is the mechanism of action of leukotriene receptor antagonists?

A
  • Leukotrienes are a derivative of the inflammatory “arachidonic cascade”.
  • The LTRAs block effects of bronchoconstricting cysteinyl luekotrienes (specifically CysLT1) in the airways, resulting in bronchodilation.
  • Reduce eosinophil recruitment to the airways, reducing inflammation, epithelial damage and airway-hyperreactivity.
    • It is particularly good in patients whose asthma has an atopic element.
  • This results in:
    • ​Decreased exercise-induced asthma.
    • Decreased both early and late phase bronchoconstrictor response to allergens.
22
Q

Under what circumstances would leukotriene receptor antagonists be prescribed?

A
  • Step 3 or 4 in the treatment ladder.
  • They should be added to a LABA or ICS.
23
Q

Give examples of leukotriene receptor antagonists.

What is their route of administration?

What are their side effects?

A
  • Taken by oral route.
  • Motelukast
  • Zafirlukast
  • Side-effects:
    • Abdominal pain
    • Headache
    • Hyperkinesia (children)
24
Q

What are methylxanthines?

Describe their mechanism of action.

A
  • Theophylline
  • Aminophylline
  • Phosphodiesterase inhibitors
    • Increased intracellular cAMP in bronchial smooth muscle → relaxation.
  • PDE implicated in inflammatory cells.
  • Methylxanthines have a bronchodilator and anti-inflammatory action.
  • Also blocks adenosine receptors resulting in bronchodilation.
25
Q

What are the side-effects of methylxanthines?

A
  • Narrow therapeutic index; dose or rate related.
    • A small dose increase can result in a massive increase in the drug concentration in the body. This can become toxic. Most of this is dose related but can also be rate related. If it is given too fast possible increased side effects due to a rate issue.
  • GI upset
  • Arrhythmias
  • CNS stimulation
  • Hypotension
26
Q

What is the indication for use of monoclonal antibodies?

‘The Mabs’

A

Used in severe persistent allergic asthma.

27
Q

Describe monoclonal antibodies.

Give an example of a Mab.

A
  • Mechanism of action:
    • ‘Preventer’
    • Injectable route
    • Slow to work - peaks at 3-4 months
    • Reduces exacerbations and it steroid sparing
    • Expensive
    • Can cause anaphylaxis and increase risk of strokes / heart disease.
  • Omalizumab - antibody to IgE, inhibits mediator release from basophils and mast cells.
28
Q

What are the 5 steps in asthma management according to the NICE guidelines?

A
  1. SABA
  2. SABA + low dose ICS
  3. SABA + low dose ICS + LTRA
  4. SABA + ICS + LABA (+/- LTRA)
    • Includes self-management by increasing ICS dose temporarily during acute events.
  5. Trial of additional drugs
29
Q

Describe a monitoring plan for an asthma patient.

A
  • Monitoring plan:
    • ​Peak expiratory flow rate
    • If <50% of predicted → severe asthma
    • Nocturnal dip is often present
30
Q

Describe the management of asthma in children.

A
  • Be careful of doses and licensing!
  • <3 years → spacer + mask
  • <5 years → PEFR is not a reliable guide
  • School age kids:
    • Educate about inhalers
    • Check in with school nurse
    • Inform teachers
  • Device type to suit child
  • Think about effects of steroids - adrenal suppression, growth retardation.
  • Remember to step down as well as up.
31
Q

What things must be remembered before starting or adjusting asthma medication?

A
  • Check diagnosis
  • Concordance
  • Technique
  • Smoking (active or passive)
  • Occupational exposures
  • Psychosocial factors
  • Seasonal or environmental factors
32
Q

What are the features of moderate acute asthma?

A
  • Increasing symptoms.
  • PEF >50-75% best or predicted.
  • No features of acute severe asthma.
33
Q

What are the features of acute severe asthma?

A
  • Any one of:
    • PEF 33-50% best or predicted
    • Respiratory rate ≥25/min
    • Heart rate ≥110/min
    • Inability to complete sentences in one breath
34
Q

What are the features of life-threatening asthma?

A
  • Any one of the following in a patient with severe asthma:
    • Altered consciousness
    • Exhaustion
    • Arrhythmia
    • Hypertension
    • Cyanosis
    • Silent chest
    • Poor respiratory effort
    • PEF <33% best or predicted
    • SpO2 <92%
    • PaO2 <8kPa
      • ‘Normal’ PaCO2 is 4.6-6.0 kPa
35
Q

What are the features of near-fatal asthma?

A
  • Raised PaCO2 and / or requires ventilation / NIV (non-invasive ventilation).
36
Q

What are the immediate treatments in the management of acute severe asthma in adults?

A
  • Oxygen (to maintain SpO2 at 94-98%).
  • Salbutamol or terbutaline plus ipratropium via nebuliser.
  • IV steroid = hydrocortisone; switch to ORAL prednisolone.
  • +/- antibiotics.
  • If patient is still not improving consider:
    • IV magnesium sulphate.
    • Switch from nebulised to IV salbutamol or aminophylline.
  • Monitor blood gases and patient exhaustion / alertness.
37
Q

How can acute severe asthma be managed if there is no nebuliser available?

A
  • If no nebuliser:
    • Salbutamol inhaler - child and adult:
      • Give 2-10 puffs. Each puff is to be inhaled separately.
      • Repeat every 10-20 minutes or when required.
      • Give via a large volume spacer (and a close-fitting mask in children under 3 years).
      • Each puff is equivalent to 100µg.
38
Q

Describe SOS I am.

A
  • Salbutamol
  • Oxygen
  • Steroid
  • Ipratropium
  • Aminophylline
  • Magnesium
39
Q

Compare and contrast asthma and COPD.

A
40
Q

List the things which are recommended for all COPD patients.

A
  • Smoking cessation - offer support - psychological + nicotine replacement / buproprion / varenicline.
  • Early use of long-acting bronchodilators (modest response only).
  • ICS - depends on FEV1 and response.
  • Immunise - pneumovax plus flu vax.
  • Pulmonary rehabilitation.
  • Self-management plan.
  • Optimise treatment for co-morbidities.
41
Q

Describe the properties of asthma-COPD overlap syndrome (ACOS).

A
  • Responds better to ICS in reducing exacerbation rate.
  • More reversible to salbutamol.
  • Difficult to distinguish from asthmatic smokers who have airway remodelling (ie reduced FVC).
  • Higher eosinophil count.
  • FEV1 swings.
  • Diurnal variation in PEFR.
42
Q

Describe the NICE-suggested management of COPD when there is no suggestion of concurrent asthma or steroid responsiveness.

A
43
Q

Describe the NICE-suggested management of COPD when there is suggestion of concurrent asthma or steroid responsiveness.

A
44
Q

Describe the action of muscarinic receptor antagonists.

A
  • Cause bronchodilation, decreased mucous secretion and may increase mucociliary clearance.
  • Improves outcomes in COPD and reduces exacerbations.
  • Slower onset of action (30-60 minutes) cf β-agonists.
  • Not effective against allergen challenge.
  • There are short- and long- acting versions.
45
Q

What are the side-effects of muscarinic receptor antagonists?

A
  • Uncommon:
    • Constipation
    • Dry mouth
    • Nausea
    • Headache
    • Cough
    • Urinary retention (men)
    • Can worsen angle closure in glaucoma
46
Q

Give examples of short- and long- acting muscarinic receptor antagonists.

A
  • SAMA - short-acting:
    • Ipratropium (acute nebulised route)
      • Nonselective
  • LAMA - long-acting:
    • Tiotropium
    • Aclidinium
      • More selective for M3 receptor
47
Q

What are the considerations of inhaled corticostaroid use in COPD?

A
  • Limited benefit.
  • Inflammatory cells responsible for COPD (macrophages and neutrophils) are less responsive than lymphocytes and eosinophils to the actions of ICS.
  • Use if FEV1< 50% predicted and have 2 or more exacerbations in a year which require antibiotics or oral steroids.
  • High doses may increase risk of pneumonia and osteoporosis.
48
Q

What are the other treatments for COPD?

A
  • Methylxanthines:
    • Theophylline
    • Aminophylline
  • Mucolytics - if chronic productive cough, reduce sputum viscosity.
    • Carbocysteine
  • Phosphodiesterase type-4 inhibitor - used if severe COPD with repeated exacerbations.
    • Roflumilast
  • Longterm antibiotics
    • Azithromycin
  • Anti-IgE monoclonal antibody
  • Long-term oxygen
49
Q

Describe how COPD is assessed.

A
  • Primarily based on patient symptoms, ADL, exercise capacity and speed of symptom relief with SABA.
  • Changes in lung function - spirometry.
  • Risk of exacerbations.
  • 2 or more exacerbations within the past year or FEV1 <50% predicted are indicators of high risk.
50
Q

How should acute severe COPD exacerbations be managed?

A
  • Nebulise SABA / SAMA
    • oral prednisolone
    • antibiotic if infected
  • Physiotherapy
  • 24-28% oxygen (with care! - watch PaO2 / PaCO2)
  • Extreme = NIV, intubation.

Respiratory (13 decks)

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