11. Pharmacology of Airway Control Flashcards
What are the components of asthma pathophysiology?
Inflammation -> mucosal oedema, bronchoconstriction, mucus plugging, and airway remodelling, and bronchial hyperresponsiveness.
In what ways is asthma a heterogenous disease?
Pathologically, symptom patterns and triggers of exacerbations, and response to treatment.
What are the five steps involved in management of asthma in adults?
Mild intermittent asthma, regular preventer therapy, add-on therapy, persistent poor control, continuous or frequent use of oral steroids.
What is meant by asthma control?
Minimal symptoms day and night, minimal need for reliever medication, no exacerbations, no limitation of physical activity, normal lung function.
Before starting a new drug therapy for asthma, what should be checked?
Compliance with existing therapies, inhaler technique, eliminate trigger factors.
What is step 1 of asthma management?
Short-acting B2-agonists - salbutamol, terbutaline.
What are the goals of step 1 in asthma management?
Symptom relief by reversing bronchoconstriction, prevent bronchoconstriction.
What is a risk of using SABAs regularly in asthma control?
They reduce control with regular use - mast cell degranulation promoted.
What is the action of SABAs?
Relax airway smooth muscle, inhibit mast cell degranulation if intermittent use.
What is the mechanism of action of SABAs?
MLCK and PKA cause relaxation and inhibition of agonist-induced contraction.
What are the ADRs of SABAs?
Adrenergic so tachycardia, palpitations, tremor.
What is step 2 of asthma management?
Inhaled corticosteroids.
When should treatment of asthma step up to step 2?
If using B2 agonist >3 times/week, symptoms >3 times/week, waking >1/week, exacerbation requiring oral steroids in last 2 years.
What is the purpose of corticosteroid use in asthma therapy?
Improve symptoms, improve lung function, reduce exacerbations, prevent death.
What is the mechanism of action of corticosteroids?
Transactivation on B2 receptors, transrepression of inflammatory mediators.
What is the systemic availability of inhaled drugs dependent on?
Drug entering systemic circulation via absorption from lungs and drug from swallowed fraction that is metabolised in gut and liver.
Which subgroup of asthma patients respond better to inhaled steroids?
Those with eosinophilic asthma.
What is step 3 of asthma management?
Long acting B2 agonist (formoterol, salmeterol), add in LABA when patients not controlled on ICS.
What are the effects of LABA used in asthma therapy?
Reduced asthma exacerbations, improved asthma symptoms, improved lung function.
Why do LABAs need to prescribed in conjunction with inhaled steroids?
They’re not anti-inflammatory on their own.
Why should LABA and ICS be combined in a single inhaler?
Easier to use, compliance, potentially cheaper, safer.
What are the alternative step 3/4 add-ons to LABA?
High dose ICS, leukotriene receptor antagonists, theophylline, tiotropium.
What is the action of LTC4 on airways?
LTC4 release by mast cells and eosinophils can cause bronchoconstriction, mucus secretion and mucosal oedema, and promotes inflammatory cell recruitment.
What is the mechanism of action of leukotriene receptor antagonists in asthma therapy?
Block effect of cysteinyl leukotrienes in airways at CysLT1 receptors.
What are the ADRs of leukotriene receptor antagonists?
Angioedema, dry mouth, anaphylaxis, arthralgia, fever, GI disturbance, nightmares
What is the mechanism of action of methylxanthines in asthma therapy?
Antagonises adenosine receptors so inhibits phosphodiesterase, increases cAMP.
Why are methylxanthines not used commonly in asthma therapy?
Poorly efficacious, narrow therapeutic window, ADRs, life-threatening toxic complications, DDIs.
What are the frequent ADRs of methylxanthines?
Nausea, headache, reflux.
What are the potentially life-threatening toxic complications of methylxanthines?
Arrhythmias, fits.
What are the DDIs of methylanthines?
Levels increased by CYP450 inhibitors.
When are LAMAs used?
COPD and severe asthma to reduce exacerbations.
What are the ADRs of LAMAs?
Dry mouth, urinary retention, glaucoma.
What is step 5 of asthma management?
Oral steroids, or biological therapies (anti-IgE or anti-IL-5).
What are the criteria for anti-IgE use in asthma therapy?
Strict - atopy, IgE in strict range.
What is the mechanism of action of anti-IgE in asthma therapy?
Prevents IgE binding to high affinity IgE receptors.
What is the effect of anti-IL-5 use in asthma therapy?
Reduces peripheral blood and airway eosinophil numbers, reduces severe asthma exacerbations.
When is stepping down recommended in asthma therapy?
Once asthma is controlled so patients are maintained at lowest possible dose of inhaled steroid.
Why does size of particles matter in drug delivery via inhaler devices?
Too big (10 micron) - deposit in mouth and oropharynx. Too small (0.5 micron) - inhaled to alveoli and exhaled without deposition in lungs. Right size (1-5 micron) - most effective as they settle in small airways.
What are the criteria for classification as severe asthma in adults?
Unable to complete sentences, pulse >110bpm, respiration >25/min, peak flow 33-50% of best/predicted.
What are life-threatening features of an asthma attack?
Severe asthma + PEF <33%, sPO2 <92, PaO2 <8kPa, PaCO2 >4.5kPa, silent chest, cyanosis, feeble respiratory effort, hypotension, bradycardia, arrhythmia, exhaustion, confusion, coma.
What is the treatment of acute severe asthma?
Oxygen high flow to keep sats 94-98%; nebulised salbutamol; oral prednisolone; nebulised ipratroprium bromide; IV aminophyllin; IV magnesium sulphate.
