Pharmacology of Airway Control Flashcards
Describe the main pathophysiological features of asthma
- TH2 driven and eosinophilic inflammation of the airways
- Inflammation leads to bronchial hyper-responsiveness and airway thickening and remodeling
- Mucosal oedema, bronchoconstriction and goblet cell hyperplasia (mucus plugging) causes constriction of airways
Describe the autonomic innervation of bronchial smooth muscle
- Parasympathetic is dominant
- Bronchoconstriction, vascular dilation, increased secretion from mucus glands
- Sympathetic non-dominant
- Only innervate vascular smooth muscle and glands so doesn’t affect airway
- ß2 adrenoceptors found in airway smooth muscle
- Only innervate vascular smooth muscle and glands so doesn’t affect airway
Describe the stepwise management of asthma
- Step 1 - infrequent, short-lived wheeze
- Short acting ß2 agonists
- Step 2 - regular preventer
- Low dose inhaled corticosteroid + short acting ß2 agonist
- Step 3a - initial add-on therapy
- Add long acting ß2 agonist as a combination inhaler to ICS
- Continue giving short acting ß2 agonist and step up dose if using 3 doses or more times a week
- Step 3b - additional add-on therapy
- If no response to LABA, stop LABA and consider increasing ICS dose
- If control still inadequate with LABA, continue LABA and increase ICS dose
- Continue giving short acting ß2 agonist and step up dose if using 3 doses or more times a week
- Step 4 - high dose therapies
- Consider increasing ICS to high dose and consider adding leukotriene receptor antagonist, aminophylline, long-acting anticholinergic
- Continue giving short acting ß2 agonist and step up dose if using 3 doses or more times a week
- Step 5 - Continuous or frequent use of oral steroids
- Daily oral steroid tablet + high dose ICS + consider other treatments (biological therapies)
- Continue giving short acting ß2 agonist and step up dose if using 3 doses or more times a week
Describe the factors of asthma control
- 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)
What should be checked before initiating a new drug therapy
- Check compliance with existing therapies
- Check inhaler technique
- Eliminate trigger factors
List some bronchodilators
- Short acting ß agonist
- Long acting ß agonist
- Leukotriene receptor antagonist
- Methylxanthines
- Long acting anticholinergics
Describe the usage and mechanism of short acting and long acting ß agonists
- Used for immediate symptom relief as prevents bronchoconstriction by relaxing airway smooth muscle
- Bind to ß2 adrenoceptors and Gs activated which causes adenylyl cyclase to convert ATP to cyclic AMP
- Cyclic AMP converted into PKA which acts to relax smooth muscle in airways
- Cyclic AMP also inhibits the myosin light chain kinase, which prevents constriction of smooth muscle
List the ADRs of short and long acting ß agonists
- (Adrenergic) - tachycardia, palpitations, tremor
Describe the mechanism of leukotriene receptor antagonists (LTRA)
- Leukotrienes are released by mast cells and eosinophils and induce bronchoconstriction, mucus secretion and mucosal oedema, and promote inflammatory cell recruitment
- LTRAs block the effect of cysteinyl leukotrienes in the airways at the CysLT1 receptor
List the ADRs of LTRA
Angioedema, dry mouth, anaphylaxis, arthralgia, fever, gastric disturbances, nightmares
Describe the mechanism of methylxanthines
- Antagonise adenosine receptors, which inhibit phosphodiesterase and increase cAMP
- Increased cAMP acts to increase bronchial smooth muscle relaxation and inhibit constriction
List the ADRs of methylxanthines
- Nausea, headache, reflux
- Life-threatening complications - arrhythmias, fits
Describe the use of leukotriene receptor antagonists and methylxanthines
- LTRA Anti-asthmatic activity not as useful and used as add-on therapy only
- Methylxanthines not as effective with narrow therapeutic window, this mainly used IV in severe/life threatening asthma as additional therapy
Describe the mechanism of long acting anticholingergics (LAMA)
Bind to M3 muscarinic receptor and block it’s action (prevent bronchoconstriction)
Describe the action of corticosteroids
- Inhaled corticosteroids act to reduce inflammation within the lungs
- Bind to transcription factors (nuclear receptors), leading to dissociation of chaperon protein
- Prevents transcription of pro-inflammatory mediators and thus reduces inflammation
