Asthma Flashcards
Asthma is due to
Chronic airway inflammation and hyperresponsiveness of airway to minute amt of irritant
What is an asthma controller
Anti inflammatory to prevent recurrent attack
What is fluticasone
Fluticasone is an inhaled corticosteroid that is used as a controller. Anti inflammatory effect
Why is fluticasone inhaled instead of given orally
Extensive first pass, clearedby liver asap if given orally
How does fluticasone exert anti inflammatory effect
Decrease inflammatory cells in airway dramatically
Decrease shedding of epithelial cells which makes airway sensitive to irritants
Increase macrophage efferocytosis
Down regulate cox2, 5-lox, pla2 at lungs, upregulate pla2 inhibitor annexin 1
Increase b2 receptor expression on airway smooth muscle for bronchodilation
As a result decrease airway hyperresponsiveness due to inflammation, prevent airway wall remodelling, decrease need for beta 2 agonist
What is 1st line prophylactic asthma therapy
Fluticasone
Side effects of fluticasone
Inhaled corticosteroid.
Immunosuppression leading to opportunistic infections eg oropharyngeal candidiasis
Dysphonia (hoarse throat), cough
Easy bruising due to skin thinning hence small bump can easily break vessel
Adrenal suppression
Post subcapsular cataracts
Osteoporosis
Growth retardation in pediatric patients
Are leukotriene receptor antagonists controllers or relievers?
Controller
Mechanism of montelukast
Montelukast inhibits leukotriene receptor as it is a competitive antagonist against cysteinyl leukotriene receptor, decreasing pathogenesis of asthma
Leukotrienes cause bronchoconstriction, airway hyper responsiveness, c fibre release of substance p, mucus hypersecretion, airway smooth muscle hyperplasia
Hence montelukast is bronchodilator and anti inflammatory
How is montelukast administered
Orally
When do use montelukast
Aspirin induced asthma (inhibit cox, increase leukotrienes)
Exercise induced asthma
Compare montelukast and fluticasone
Montelukast less effective than ICS
But steroid sparing
Side effects of montelukast
Rare psychological reaction, resulting in agitation, hallucination, depression
What does sodium cromoglycate do
Asthma controller
Mast cell stabiliser, inhibits mast cell degranulation induced by IgE cross linking with fcE receptor
Promote annexin 1 secretion, inhibit pla2 and block histamine and eicasanoid release from mast cells
Blocks antigen/exercise induced bronchospasm
No bronchodilator effect
How is sodium cromoglycate administered
Inhaled solution only for prophylactic control of asthma
Nasal spray/ophthalmic prep for allergic reaction/conjunctivitis
What are the side effects of sodium cromoglycate
Throat irritation, mouth dryness, coughing (preventable by inhaling b2 agonist first)
Bitter unpleasant taste
What does anti IgE monoclonal antibody do
Asthma controller. Depletes igE, prevent mast cell degranulation and decrease mediator release
Anti IgE mab bind IgE to block IgE from binding to receptor
Downregulate fce1 receptor expression
Sodium cromoglycate and monoclonal antibodies used for what type of asthma
Antigen induced asthma eg allergic asthma, allergic rhinitis
What does anti il5/5r and anti il4r mab do
Anti il5/5r blocks il5 and reduces eosinophil function
Anti il4r blocks il4 and il13 function
What are some disadvantages of using monoclonal antibodies
Expensive, only for allergic asthma, delivered subcutaneously (no inhalation/oral)
What is an asthma reliever what are the three types of relievers
Bronchodilator for rescue therapy
B2 agonist, theophylline, muscarinic antagonist
What does salbutamol do
B2 agonist, binds to b2 GPCR. Activate adenylnyl cyclase, increase cyclic amp. Decreases intracellular Ca2+ and MLCKinase, increases K+ efflux causing hyperpolarisation. This results in airway smooth muscle relaxation
Mast cell stabilisation
Reduce edema by decreasing microvascular leakiness
Increase mucociliary clearance
Compare salbutamol, formoterol, indacaterol, salmeterol
Salbutamol is short acting, formoterol and salmeterol long acting (12h) indacaterol long acting (24h)
Indacaterol is used to treat COPD only
Salbutamol is hydrophilic, f and salm amphiphilic, indacaterol is lipophilic
Indacaterol slow onset the rest are rapid onset
Describe ICS-LABA combination therapy
Used for long term maintenance of nocturnal asthma. Ics-formoterol is reliever of choice. Use Saba salbutamol as reliever/rescue therapy when patient is on ICS-LABA maintenance
Side effects of b2 agonists
Fine tremor or skeletal muscle when high dose given (tremor is first sign of overdose)
Leg cramps
Peripheral vasodilatation
Cross react with b1 receptor at the heart to cause aspirations, tachycardia
Hyperglycemia and hypokalemia at the liver
What happens if LABA b agonist is given alone
Asthma related death. B2 downregulated hence rescue therapy not effective
Need to give with ics that increases b2 expression on airway smooth muscle
How is theophylline administered
Given systemically via tablet or iv
3 mechanisms of theophylline
- Inhibit phosphodiesterase to prevent breakdown of cAMP —> decrease intracellular K+, decrease MLCK, increase hyperpolarisation via K+ efflux —> airway smooth muscle relaxation
- inhibit GPCR adenosine receptor as adenosine can cause asm contraction
- increase epinephrine release from adrenal medulla to bind to b2
Describe use of theophylline
Less effective bronchodilator than b2 agonist
Add on therapy to ics-formoterol combination
Increases contractility of fatigue diaphragm to improve lung function in COPD
Side effects of theophylline
Narrow ti, potential drug drug interaction (ciprofloxacin inhibits metabolism of theophylline)
Anorexia, abdominal discomfort, arrhythmia
Name examples of muscarinic antagonists
Ipratropium bromide (short acting)
Tiotropium bromide (long acting)
Mechanism of action of muscarinic antagonists
Bronchodilator/reliever
Decrease mucus secretion
Anti inflammatory because Ach binds to musc receptor of inflammatory cel to trigger inflammation
Inhibit m3 receptor mediated bronchoconstriction
When are muscarinic antagonists used
Add on therapy to ICS+B2 or when patient intolerant to b2 agonists
More effective for COPD `
Side effects of muscarinic antagonists
Urinary retention, dry mouth
Paradoxical bronchospasm
Unpleasant taste (like sodium cromoglycate)
