Asthma Flashcards
What are example of long acting beta agonists?
- Formoterol: rapid onset and long duration
- Salmeterol: slow onset and long duration
What are examples of short acting beta agonists?
- Salbutamol
- Terbutaline
What is the mechanism of action of Beta 2 agonists?
- Binds to Beta 2 adrenoreceptor
- Increases in Adenycylase activity
- Increase in cAMP t inhibit the MLCK so relaxation
- Increase in pKA to cause relaxation
What are the uses of Beta 2 receptor agonists?
- Used for symptom relief through reversal of bronchoconstriction (mild intermittent asthma)
- Prevention of bronchoconstriction i.e. on exercise
- Used as required basis
What are some side effects of beta 2 receptor agonists?
-If used regularly, they reduce asthma control
Mast cell degranulation in response to allergen increases if beta 2 agonist used regularly
-Adrenergic so can cause tachycardia, palpitations, tremor
What are examples of inhaled corticosteroids?
- Beclomethasone
- Budesonide
- Prednisolone
- Dipropionate
- Fluticasone
Describe the pharmacokinetics of Beclomethasone?
-Absorbed through gut and lungs
Describe the pharmacokinetics of Budesonide?
-Undergoes extensive first-pass metabolism
Describe the pharmacokinetics of Fluticasone?
-Undergoes extensive first-pass metabolism
What is the mechanism of action of inhaled corticosteroids?
Works by binding to Glucocorticoid recetor which affects gene in the nucleus afterwards to cause:
Transactivation
- Stimulation of anti-inflammatory molecules such as Annexin-1
- Increase in b2 receptors
Transpression
-Inhibition of pro-inflammatory mediators such as cytokines, chemokines, iNOS
What are the properties of adding lipophilic substituents to inhaled corticosteroids?
- A very high affinity for the GCS receptor
- Increased uptake and dwell time in tissue on local application
- Rapid inactivation by hepatic biotransformation following systemic absorption
What are the uses of Inhaled corticosteroids?
- Improve symptoms
- Improve lung function
- Reduce exacerbations
- Prevent death
Better treatment response from eosinophilic patients
What are examples of Leukotriene Receptor antagonists?
- Montelukast
- Zafirlukast
What is the mechanism of action of Leukotriene receptor antagonists?
-Block the effect of cysteinyl leukotirences which are released by mast cells and eosinophils and cause bronchoconstriction, mucus secretion and mucosal oedema and promote inflammatory cell recruitment
What are the use of leukotriene receptor antagonists?
Some anti-asthma activity but only useful in about 15% patients as add-on therapy
What some side effects of leukotriene receptor antagonists?
- Angioedema
- Dry mouth
- Anaphylaxis
- Arthralgia
- Fever
- Gastric Disturbance
- Nightmares
What are examples of Methylxanthines?
- Theophylline
- Aminophylline
What is the mechanism of action of Methylxanthines?
- Anatagonise adenosine receptors
- Inhibit phosphodiesterase so increased cAMP. Unlke to be relevant in vivo
What are the pharmacokinetics of Methylxanthines?
- Poorly efficacious
- Narrow therapeutic window
What are the uses of Methylxanthines?
-Asthma
What are the side effects of Methylxanthines?
- Nausea
- Headache
- Reflux
- Arrythmias
- Fits
- Levels increase with CP450 inhibitorsr
What are examples of LAMAs?
- Tiotropium bromide
- Ipratropium Bromide
What is the mechanism of action of LAMAs?
- Anticholinergic used once daily
- Relative selectivity for M3 muscurinic receptor
When are LAMAs used?
- COPD
- Severe asthma
- Reduction of exacerbation in both and small improvement in lung function and symptoms
