Respiratory pharmacology Flashcards

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1
Q

Define asthma

A
  • Chronic inflammatory airway disease
  • Intermittent airway obstruction
  • Hyper-reactivity of small airways
  • Reversible (spontaneously or due to drugs)
  • heterogenous disease
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2
Q

What are the aims of asthma control?

A
  • Minimal symptoms during day at night
  • Minimal needs for reliever medication
  • No exacerbations
  • No limitation of physical activity
  • Normal lung function
  • Early control with stepping up or down as required
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3
Q

What do we need to check before stepping a patient’s asthma treatment up?

A
  • Adherence
  • Inhaler technique
  • Remove triggers
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4
Q

Give a brief outline of the treatment ladder for asthma

A
  1. Regular preventer - low dose ICS
  2. Initial add-on therapy - add inhaled LABA to low dose ICS
  3. Additional controller therapies - consider increasing ICS to medium dose or adding LRTA
  4. Specialist therapies
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5
Q

What indicates that a patient needs to move up the treatment ladder for asthma?

A
  • All asthma patients are given a short acting B2 agonist to use as needed
  • Consider moving up if using 3+ doses per week
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6
Q

What are the current NICE guidelines for managing asthma in adults?

A
  • Add LRTA (leukotriene receptor antagonist) after initial low dose LABA
  • LRTA is cheaper than LABA
  • Though LABA is more effective
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7
Q

Give some examples of inhaled corticosteroids

A
  • Beclomethasone
  • budesonide
  • Fluticasone
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8
Q

What is the mechanism of action of inhaled corticosteroids?

A
  • Pass through plasma membranes
  • Activate cytoplasmic receptors
  • Activated receptor passes into nucleus to modify transcription
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9
Q

What are the effects of inhaled corticosteroids on the airways?

A
  • Reduces mucosal inflammation
  • Widens airways
  • Reduces mucus
  • Reduces symptoms, exacerbations and prevents death
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10
Q

What are the adverse side effects of inhaled corticosteroids?

A
  • Can cause a local immunosuppressive action - candidiasis, hoarse voice
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11
Q

What are the contraindications for inhaled corticosteroids?

A
  • Pneumonia risk possible in COPD at high doses
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12
Q

What are the DDIs of inhaled corticosteroids?

A
  • There aren’t really any
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13
Q

Which genes are activated by inhaled corticosteroids?

A
  • Increased B2 receptors
  • Anti inflammatory mediators
  • Also inhibit release of arachidonic acid
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14
Q

Which genes are repressed by inhaled corticosteroids?

A
  • Those that code for inflammatory mediators
  • E.g. interleukins, chemokines, cytokines
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15
Q

Outline the pharmacokinetics of inhaled corticosteroids

A
  • Poor oral bioavailability
  • Slow dissolution in aqueous bronchial fluid
  • High affinity for glucocorticoid receptor
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16
Q

What happens when a steroid is absorbed p.o.?

A
  • Transported from stomach to liver by hepatic portal system
  • Almost complete first pass metabolism
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17
Q

Give some examples of fast-acting B2 agonists?

A
  • Salbutamol and terbutaline (short lasting)
  • Formoterol (long lasting)
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18
Q

Give some examples of long-acting B2 agonists?

A
  • Salmeterol (long lasting)
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19
Q

What are the different types of B2 agonists?

A
  • Short acting B2 agonists (SABA) - symptom relief through reversal of bronchoconstriction
  • Long acting B2 agonists (LABA) - add on therapy to ICS and SABA
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20
Q

What is the mechanism of action of B2 agonists?

A
  • Major action on airway smooth muscle
  • Also increase mucus clearance by action of cilia
  • Prevents bronchoconstriction prior to exercise
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21
Q

Why shouldn’t patients use an SABA too often?

A
  • Can reduce asthma control
  • Tolerance might build
22
Q

What are the adverse side effects of B2 agonists?

A
  • Adrenergic - fight or flight effects
  • Tachycardia
  • Palpitations
  • Anxiety and tremor
  • Increased glycogenolysis
  • Increased renin
23
Q

What are the contraindications of B2 agonists?

A
  • LABA should only be prescribed alongside ICS
  • LABA given alone can mask airway inflammation and near-fatal/fatal attacks
  • CVD - tachycardia may provoke angina
24
Q

What are some problems with LABAs?

A
  • Need to be given in a combined fixed dose inhaler (ICS + LABA)
  • Adherence
  • Cost
  • Safety
25
Q

What are the DDIs of LABAs?

A

B blockers may reduce effects of B2 agonists

26
Q

What are some controller therapies for asthma?

A
  • Leukotriene receptor antagonists
  • Long acting muscarinic antagonists
27
Q

Give an example of a leukotriene receptor antagonist (LRTA)

A
  • Montelukast
28
Q

What is the mechanism of action of leukotriene receptor antagonists?

A
  • Leukotrienes released by mast cells/eosinophils
  • Increased bronchoconstriction, mucus, and oedema through CysLT1 - a GPCR
  • LRTAs block CysLT1
29
Q

What are the adverse side effects of leukotriene receptor antagonists?

A
  • Headache
  • GI disturbance
  • Dry mouth
  • Hyperactivity
30
Q

What are the contraindications for LRTAs?

A
  • Neuropsychiatric reactions
31
Q

What are the DDIs for LRTAs?

A
  • None reported
32
Q

Give some examples of long acting muscarinic antagonists (LAMA)

A
  • Tiotropium
  • Theophylline
33
Q

What are the indications of tiotropium?

A
  • Severe asthma
  • COPD
34
Q

What is the mechanism of action of tiotropium?

A
  • Block vagally mediated contraction of airway smooth muscle
35
Q

What are the adverse side effects of tiotropium?

A
  • Infrequent
  • Anticholinergic effects
  • E.g. dry mouth, urinary retention, dry eyes
  • Generally ok for most with inhaled route
36
Q

What are the indications for theophylline?

A
  • p.o.
  • Poorly controlled asthma
37
Q

What is the mechanism of action of theophylline?

A
  • Adenosine receptor antagonist
  • Decreased bronchoconstriction
  • Phosphodiesterase inhibitor
  • Taken on short term basis alongside ICS, LABA or muscarinic antagonist
38
Q

What are the contraindications of theophylline?

A
  • Narrow therapeutic index
  • Potentially life-threatening complications including arrhythmia - must measure plasma concentration
39
Q

What are the DDIs of theophylline?

A
  • CYP450 inhibitors increase concentration of theophylline
40
Q

Why are self-management plans given to asthmatic patients?

A
  • For all asthmatic patients
  • Written instructions on when and how to step up and down treatment
  • Allows better day to day management and reduced exacerbations
41
Q

What values indicated that asthma is acute or severe?

A
  • Unable to complete sentences
  • Peak flow 33-50% best or predicted
  • Respiratory rate > 25/min
  • Heart rate >110/min
42
Q

Which values make asthma life-threatening?

A
  • All criteria for acute and severe asthma plus one of the following:
  • Peak flow <33% best or predicted
  • Arterial oxygen saturation <92%
  • PaO2 <8kPa
  • Normal PaCO2 4.6-6.0 kPa
  • Silent chest
  • Cyanosis
  • Poor respiratory effort
  • Arrhythmia
  • Exhaustion
43
Q

Which medications should be given in acute severe and life-threatening asthma?

A
  • Oxygen
  • High dose nebulised B2 agonist (oxygen driven)
  • Prednisolone
  • Ipratropium
  • Consider i.v. aminophylline if life-threatening/near fatal and no success with the above
44
Q

What type of drug is prednisolone?

A
  • Oral steroid
  • Continue ICS alongside
45
Q

What type of drug is ipratropium?

A
  • Taken nebulised as ipratropium bromide
  • Short acting muscarinic antagonist
  • Take alongside B2 agonist if poor response alone
46
Q

What are the 5 tasks of management of COPD?

A
  • Confirm diagnosis
  • Smoking cessation
  • Breathlessness score
  • Vaccination
  • Medication
47
Q

What medications are given to COPD patients suffering from acute exacerbations and requiring hospitalisation?

A
  • Nebulised salbutamol and/or ipratropium
  • If patient is hypercapnic or acidotic, nebuliser should be driven by air
  • Oral steroids
  • Antibiotics
  • Review of chronic treatment and action plan
48
Q

What factors influence which inhalers you prescribe?

A
  • Need to find an inhaler that the patient can use
  • Should be assessed by an appropriately trained healthcare professional
  • Dose needs to be titrated against clinical response
  • Reassessed as part of regular medication review
49
Q

What are some different types of inhaler that can be prescribed?

A
  • Pressurised metered dose inhalers (pMDI)
  • Breath-actuated pMDI
  • Dry powder inhalers
  • Inhalers often prescribed by brand and not generic
50
Q

Why is inhalation technique important?

A
  • Inhaler, technique and drug formulation dictate particle size and deposition
  • If inspiratory flow is too slow, drug deposits in mouth
  • But if it’s too fast, drug deposits in the throat
  • If drug is too small it is inhaled to the alveoli and then exhaled without being deposited
  • If drug id too big, it is deposited in the mouth and oropharynx
51
Q

How can we check a patient’s inhaler technique?

A
  • In-check DIAL device