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SA Clinical Pharmacology & Therapeutics > S11) Pharmacology of Airway Control > Flashcards

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
Describe the mechanism of action for long acting anticholinergics
LAMAs bind to M3 muscarinic receptor and block it’s action (prevent bronchoconstriction)
26
What are the ADRs of LAMAs?
**Anticholinergic** – dry mouth, urinary retention, glaucoma
27
Describe the mechanism of action of omalizumab (anti-IgE)
**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
Describe the mechanism of action of reslizumab (Anti IL-5)
**Biological therapies:** - Reduce peripheral blood and airway eosinophil numbers - Most effective at reducing rate of severe asthma exacerbations
29
what are ICS, how do they work and what do they do?
- 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
what are some examples of ICS's
beclomet**asone ** budesonide flutic**asone **
31
what are some warnings, adverse reactions and drug-drug intercations with ICS
can cause local immunosuppresant actions (candidiasis, horse voice) pneumonia risk if taken correctly there will be few ADRs
32
steroids mechanism of action
-> 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
pharmacokinetics of ICS
-> **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
why does LABA have to be used as an add on with ICS
-> 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
what is the role of theophylline as an additional controller therapy
-> **chronic poorly controlled asthma** -> **adenosine receptor antagonis**t 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
what are the stats for severe and life threatning asthma
-> cant speak full sentences -> peak flow 33-50% -> resp rate >25/min -> heart rate >110/min
37
which medication should be given to someone suffering from a severe asthma attack
**Prednisolone and ipratropium ** ipratropium is a SAMA can consider IV aminophylline if life threatning
38
which medication should be given to someone suffering from a severe asthma attack
**Prednisolone and ipratropium ** ipratropium is a SAMA can consider IV aminophylline if life threatning
39
what medications should be given to someone suffering from an acute exacerbation of COPD
-> nebulised salbutamol and/or ipratropium
39
what medications should be given to someone suffering from an acute exacerbation of COPD
-> nebulised salbutamol and/or ipratropium
40
before changing someones asthma prescription what should you check
1. adherance to meds 2. inhaler techniques (most people use it wrong) 3. remove any triggers (animals, allergies)
41
what are the different inhaler options
* 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
what size are the particles of the asthma medication if they reach the mouth, throat and lungs
43
what device can be used to check for correct inspiratory flow
DIAL device
44
why do ICS have reduced systemic effects at theraputic doses
they have a topical action, so they are localised
45
molecule size
too small; inhaled and exhaled too big will just deposit into the mouth and oropharynx
46
acute severe asthma attack
cant complete sentence pulse above 110 resp above 25
47
what dose is best for steroid
lowest

SA Clinical Pharmacology & Therapeutics (36 decks)

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