S11) Pharmacology of Airway Control Flashcards
Describe the autonomic innervation of the airway smooth muscle
- 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)
What does asthma control mean?
- 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)
Outline the stepwise treatment approach for asthma
- 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
What is used to treat mild intermittent asthma in Step 1 of asthma control?
Mild intermittent asthma – short-acting β2-agonists e.g. salbutamol, terbutaline
Describe the Step 1 treatment aims in asthma control
- Symptom relief through reversal of bronchoconstriction
- Used on an as-required basis (not regularly)
Describe the site and/or mechanism of action of β2 agonists in Step 1 of asthma control
- Acts predominantly on airway smooth muscle (brochodialator)
- Potentially inhibits mast cell degranulation (if used intermittently)
- increase mucus clearance by cilia
Illustrate the β2 receptor function in airway smooth muscle
Classify the different inhaled β2 agonists in terms of the speed of onset and the duration of action
LABA: add on therapy to ICS and SABA
Identify some side effects of β2 agonists
Adrenergic increased activation of SA node i.e. tachycardia, palpitations, tremor, increased glycogenolysis in liver and renin in the kidney
What is used as regular preventer therapy in Step 2 of asthma control?
Regular preventer therapy – inhaled corticosteroids
What are the four conditions one must consider before starting Step 2 in the asthma control for a patient?
- Using β2 agonist ≥ 3 times/week
- Symptoms ≥ 3times/week
- Waking ≥ 1time/week
- Exacerbation requiring oral steroids in last 2 years
What are the aims of Step 2 treatment in asthma control?
- Improve symptoms
- Improve lung function
- Reduce exacerbations
- Prevent death
Illustrate the systemic availability of inhaled drugs
Provide some examples of inhaled corticosteroids
- Budesonide
- Beclomethasone
- Fluticasone
Provide an example of a combined LABA and steroid
Symbicort
Provide an example of a leukotriene receptor antagonists
Montelukast
What are some ADRs for leukotriene receptor antagonists?
- Angioedema
- Dry mouth
- Anaphylaxis
- Arthralgia
- Fever
Describe the mechanism of action for LTRAs
- 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
Provide some examples of methylxanthines
- Theophylline
- Aminophylline
Describe the mechanism of action for methylxanthines
- Antagonise adenosine receptors
- Inhibit phosphodiesterase
- Increase cAMP
What are the ADRs for methylxanthines?
- Common – nausea, headache, reflux
- Potentially life-threatening toxic complications – arrhythmias, fits
What possible drug interactions might methylxanthines have?
Levels increased by CYP450 inhibitors e.g. erythromycin, ciprofloxacin
Provide some examples of long acting anticholinergics (LAMA)
- Tiotropium bromide
- Glycopyrronium
What are the indications for LAMAs?
- COPD
- Severe asthma
Describe the mechanism of action for long acting anticholinergics
LAMAs bind to M3 muscarinic receptor and block it’s action (prevent bronchoconstriction)
What are the ADRs of LAMAs?
Anticholinergic – dry mouth, urinary retention, glaucoma
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
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
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
what are some examples of ICS’s
beclometasone **
budesonide
fluticasone **
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
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
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
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
what is the role of theophylline as an additional controller therapy
-> 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
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
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
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
what medications should be given to someone suffering from an acute exacerbation of COPD
-> nebulised salbutamol and/or ipratropium
what medications should be given to someone suffering from an acute exacerbation of COPD
-> nebulised salbutamol and/or ipratropium
before changing someones asthma prescription what should you check
- adherance to meds
- inhaler techniques (most people use it wrong)
- remove any triggers (animals, allergies)
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
what size are the particles of the asthma medication if they reach the mouth, throat and lungs
what device can be used to check for correct inspiratory flow
DIAL device
why do ICS have reduced systemic effects at theraputic doses
they have a topical action, so they are localised
molecule size
too small; inhaled and exhaled
too big will just deposit into the mouth and oropharynx
acute severe asthma attack
cant complete sentence
pulse above 110
resp above 25
what dose is best for steroid
lowest
