S11) Pharmacology of Airway Control Flashcards

1
Q

Describe the autonomic innervation of the airway smooth muscle

A
  • Parasympathetic (dominant) – bronchoconstriction, vascular dilatation, increased secretion from mucus glands
  • Sympathetic – innervates vascular smooth muscle & glands (doesn’t affect airway, but β-adrenoreceptors found in airway smooth muscle)
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2
Q

What does asthma control mean?

A
  • Minimal symptoms during day and night
  • Minimal need for reliever medication
  • No exacerbations
  • No limitation of physical activity
  • Normal lung function (FEV1 and/or PEF >80% predicted or best)
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3
Q

Outline the stepwise treatment approach for asthma

A
  • Step 1 – short acting β2 agonists, consider low dose ICS (Inhaled corticosteroids)
  • Step 2 – regular low dose ICS
  • Step 3

A. LABA + low dose ICS

B. LABA + ↑ dose ICS / stop LABA if no effect

  • Step 4 – LABA + high dose ICS (can add LTRA/aminophylline)
  • Step 5 – daily oral steroid + high dose ICS + consider others
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4
Q

What is used to treat mild intermittent asthma in Step 1 of asthma control?

A

Mild intermittent asthma – short-acting β2-agonists e.g. salbutamol, terbutaline

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5
Q

Describe the Step 1 treatment aims in asthma control

A
  • Symptom relief through reversal of bronchoconstriction
  • Used on an as-required basis (not regularly)
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6
Q

Describe the site and/or mechanism of action of β2 agonists in Step 1 of asthma control

A
  • Acts predominantly on airway smooth muscle (brochodialator)
  • Potentially inhibits mast cell degranulation (if used intermittently)
  • increase mucus clearance by cilia
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7
Q

Illustrate the β2 receptor function in airway smooth muscle

A
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8
Q

Classify the different inhaled β2 agonists in terms of the speed of onset and the duration of action

A

LABA: add on therapy to ICS and SABA

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9
Q

Identify some side effects of β2 agonists

A

Adrenergic increased activation of SA node i.e. tachycardia, palpitations, tremor, increased glycogenolysis in liver and renin in the kidney

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10
Q

What is used as regular preventer therapy in Step 2 of asthma control?

A

Regular preventer therapy – inhaled corticosteroids

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11
Q

What are the four conditions one must consider before starting Step 2 in the asthma control for a patient?

A
  • Using β2 agonist ≥ 3 times/week
  • Symptoms ≥ 3times/week
  • Waking ≥ 1time/week
  • Exacerbation requiring oral steroids in last 2 years
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12
Q

What are the aims of Step 2 treatment in asthma control?

A
  • Improve symptoms
  • Improve lung function
  • Reduce exacerbations
  • Prevent death
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13
Q

Illustrate the systemic availability of inhaled drugs

A
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14
Q

Provide some examples of inhaled corticosteroids

A
  • Budesonide
  • Beclomethasone
  • Fluticasone
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15
Q

Provide an example of a combined LABA and steroid

A

Symbicort

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16
Q

Provide an example of a leukotriene receptor antagonists

A

Montelukast

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17
Q

What are some ADRs for leukotriene receptor antagonists?

A
  • Angioedema
  • Dry mouth
  • Anaphylaxis
  • Arthralgia
  • Fever
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18
Q

Describe the mechanism of action for LTRAs

A
  • LTRAs (leukotriene receptor antagonist) lock the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor
  • Leukotrienes are released by mast cells/eosinophils, induce bronchoconstriction, mucus secretion and mucosal oedema and promote inflammatory cell recruitment
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19
Q

Provide some examples of methylxanthines

A
  • Theophylline
  • Aminophylline
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20
Q

Describe the mechanism of action for methylxanthines

A
  • Antagonise adenosine receptors
  • Inhibit phosphodiesterase
  • Increase cAMP
21
Q

What are the ADRs for methylxanthines?

A
  • Common – nausea, headache, reflux
  • Potentially life-threatening toxic complications – arrhythmias, fits
22
Q

What possible drug interactions might methylxanthines have?

A

Levels increased by CYP450 inhibitors e.g. erythromycin, ciprofloxacin

23
Q

Provide some examples of long acting anticholinergics (LAMA)

A
  • Tiotropium bromide
  • Glycopyrronium
24
Q

What are the indications for LAMAs?

A
  • COPD
  • Severe asthma
25
Q

Describe the mechanism of action for long acting anticholinergics

A

LAMAs bind to M3 muscarinic receptor and block it’s action (prevent bronchoconstriction)

26
Q

What are the ADRs of LAMAs?

A

Anticholinergic – dry mouth, urinary retention, glaucoma

27
Q

Describe the mechanism of action of omalizumab (anti-IgE)

A

Biological therapies:

  • Prevents IgE binding to high affinity IgE receptor
  • Cannot bind to IgE already bound to receptor, so cannot cross-link IgE and activate mast cells
28
Q

Describe the mechanism of action of reslizumab (Anti IL-5)

A

Biological therapies:

  • Reduce peripheral blood and airway eosinophil numbers
  • Most effective at reducing rate of severe asthma exacerbations
29
Q

what are ICS, how do they work and what do they do?

A
  • inhaled corticosteriods
  • pass through plasma membrane and activate cycoplasmic receptors, then actuvated receptor passeses into nucleus to modify transcription
  • reduce mucosal inflammation, widen airways
  • reduce symptoms
30
Q

what are some examples of ICS’s

A

beclometasone **
budesonide
flutic
asone **

31
Q

what are some warnings, adverse reactions and drug-drug intercations with ICS

A

can cause local immunosuppresant actions (candidiasis, horse voice)
pneumonia risk
if taken correctly there will be few ADRs

32
Q

steroids mechanism of action

A

-> gene repression of inflammaotry mediators, interleukins, chemokines
-> gene activation of B2 receptors which are anti-inflammatory mediators, also inhibit release of arachidonic acid (stop production of prostacyclin) therefore they work beyond COX inhibition

33
Q

pharmacokinetics of ICS

A

-> poor oral bioavailbility **
lipophilic chain is added on the end, High affinity for glucocorticoid receptor **
if it is taken p.o then transported from stomach to liver where it will almost complete first pass metabolism -> not ideal
this way it is good for
inhalation
and dissolves very slowly in aqeuous bronchial fluid

34
Q

why does LABA have to be used as an add on with ICS

A

-> can mask airway inflammation, and near fatal and fatal attacks
can provoke angina
TOGETHER: these are the best combination to give people with asthma as thet have the best success rate

35
Q

what is the role of theophylline as an additional controller therapy

A

-> chronic poorly controlled asthma
-> adenosine receptor antagonist andphosphodoesterse inhibitor, inhibits CAMP and activates PKA, so reduces vasconstriction and a PDE inhibitor
-> has a narrow theraputic index so can cause arrhythmias if incorrect amount given
->** CYP450 inhibitors** can** increase** concs of this

36
Q

what are the stats for severe and life threatning asthma

A

-> cant speak full sentences
-> peak flow 33-50%
-> resp rate >25/min
-> heart rate >110/min

37
Q

which medication should be given to someone suffering from a severe asthma attack

A

**Prednisolone and ipratropium **
ipratropium is a SAMA
can consider IV aminophylline if life threatning

38
Q

which medication should be given to someone suffering from a severe asthma attack

A

**Prednisolone and ipratropium **
ipratropium is a SAMA
can consider IV aminophylline if life threatning

39
Q

what medications should be given to someone suffering from an acute exacerbation of COPD

A

-> nebulised salbutamol and/or ipratropium

39
Q

what medications should be given to someone suffering from an acute exacerbation of COPD

A

-> nebulised salbutamol and/or ipratropium

40
Q

before changing someones asthma prescription what should you check

A
  1. adherance to meds
  2. inhaler techniques (most people use it wrong)
  3. remove any triggers (animals, allergies)
41
Q

what are the different inhaler options

A
  • pressurised metered dose inhalers (pMDI): slow breath in and hold
  • Breath-actuated pMDI: automatic actuation upon inhalation
  • dry powdered inhalers (DPI): micro ionised drug plus carried powder
42
Q

what size are the particles of the asthma medication if they reach the mouth, throat and lungs

A
43
Q

what device can be used to check for correct inspiratory flow

A

DIAL device

44
Q

why do ICS have reduced systemic effects at theraputic doses

A

they have a topical action, so they are localised

45
Q

molecule size

A

too small; inhaled and exhaled
too big will just deposit into the mouth and oropharynx

46
Q

acute severe asthma attack

A

cant complete sentence
pulse above 110
resp above 25

47
Q

what dose is best for steroid

A

lowest