Flashcards in Asthma Treatments Deck (32):
What are the two main (firs line ) drugs used to treat asthma?
- glucocorticoids (steroids)
- B2 adrenergic agonists
What are the two types of asthma?
- recurrent attacks of reversible airway obstruction
- controlled with drugs
- not easily reversible
- can be fatal
What is asthma?
- inflammation in the airways
- hyper-reactivity of bronchioles eg. to irritant chemicals, cold air, stimulant drugs
- results in bronchoconstriction and mucus secretion
Asthma has two stages in an attack, bronchospasm and late phase with is the inflammation. What drugs are needed in these two phases?
- bronchodilator for bronchospasm stage
- anti- inflammatory for late stage
There are short and long acting b2 adrenergic receptor agonists. What are examples of these?
- short acting
- max effect within 30 min (lasts 4-6 hours)
- used as needed to control symptoms
- long acting
- duration of action = 12 hours
- twice daily dose in patients not controlled with glucocorticoids
What are the actions of B2 adrengic receptor agonist such as salbutamol and salmeterol?
- direct action on B2 adrenoceptors on bronchiole smooth muscle to relax muscle
- inhibit mediator release from mast cells & monocytes
- may act on cilia to increase mucus clearance
B2 agonist are administered through inhalation to target action in lung & minimise systemic effects. What are the unwanted effects of these drugs?
- results from absorption into systemic circulation
- most common is tremor
- some tolerance to B2 agonist may develop - prevented by glucocorticoids
Theophylline are used with steroid when asthma response to B2 agonist is inadequate. What are the mechanisms of action in these drugs?
- mechanism is still unclear
- phosphodiesterase (PDE) inhibitor
Theophtlline is a second line drug (sustained- release tablet. it can also be given IV in acute severe asthma. What are the unwanted side effects of Theophylline?
- CNS: stimulant (tremor, sleep disturbance)
- Cardiovascular: stimulate heart, vasodilation
- GI tract: anorexia, nausea, vomiting
What is the main muscarinic receptor antagonist used?
What are the mechanism of action in muscarinic receptor antagonist such as ipratropium?
- block action of endogenous acetylcholine at muscarinic receptors
- this relaxes bronchial smooth muscles
- inhibits elevated mucus secretion in asthma
- may increase clearance of bronchial secretions
muscarinic receptor antagonists are used when B2 agonists and steroids are insufficient. What are the unwanted side effects ?
- few unwanted side effects and are mostly safe and well tolerated
What are examples of leukotriene receptor antagonists?
- montelucast (1 X daily)
- Zafirlukast (2 X daily )
leukotriene receptor antagonist such as montelucast and Zafirlukast are used for what?
- to prevent exercise induced and asprin sensitive asthma
- main use as add on for uncontrolled, mild- moderate asthma.
- action addictive with B2 agonist
What are the actions of leukotriene antagonist such as montelucast and Zafirlukast?
- act at cysteinyl-leukotriene receptors - on bronchiole smooth muscle cells
- prevent actions of LTC4, LTDD, which are:
- bronchial spasmogens
- stimulate mucus secretion
What are the unwanted side effects of leukotriene antagonist?
- very few
- GI disturbance
Glucocorticoids are anti-inflammatory drugs that are usually given by inhalation. Give examples of these drugs.
- Fluticasone propionate
- Ocassionally prednisolone or hydrocortisone
What are the actions of glucocorticoids such as beclometasone, budesonide, fluticasone propionate?
- reduce production of cytokines, spasmogens (LTC4, LTD4) and leucocyte chemotaxins (LTB4, PAF)
- therefore reduction in bronchospasm
- reduction in recruitment and activation of inflammatory cells
How long do glucocorticoids take to work?
full effect takes several days to develop
What are the detailed mechanisms of how glucocorticoids do their actions?
- enter cells
- bind to intracellular receptors in cytoplasm (GRa, GRB)
- receptor complex moves to nucleus
- binds to DNA in nucleus
alters gene transcription
eg. introduction of lipocortin, repression of IL-3
What are the clinical uses of glucocorticoids?
- patients requiring regular bronchodilators to control attacks
- IV hydrocorticoids and oral prednisolone for acute exacerbations
- short course prednisolone if deterioration or prolonged use needed for some patients
- give inhaled steroid, with additional agent for severe asthma eg. budesonide + B2 agonist or theophylline
What are the unwanted side effects of glucocorticoids such as beclometasone, budesonide, fluticasone propionate?
- oropharyngeal thrush and dysphonia, this is reduced by using spacer device as it:
- reduces oropharyngeal drug deposition
- increases airways drug deposition
- Other side effects of the glucocorticoids are:
- adrenal suppression
- patients should carry steroid card
Cromoglicate/ nedocromil cab reduce both early and late phase responses. it reduce bronchial hyper-reactivity. What is it effective against?
effective in asthma caused by
Not all asthmatics respond
- its unpredictable
- children respond better than adults
Cromoglicate mechanisms are not fully understood. what do we know about their actions?
- mast cell stabiliser
- may reduce neuronal reflexes (desensitise to irritants)
- inhibit release of T-cell cytokines
- affect inflammatory cells and mediators
What are the unwanted side effects of cromoglicate mechanisms
- irritation of upper respiratory tract
- hypersensitivity reactions reported, but rare
Cromoglicate is given by inhalation. What are the clinical uses?
- to prevent both phases of attack
- most effective in children
- effects may take weeks to develop
A new development of biologic agent is omalizumab (Xolair) what are its actions?
- binds to human IgE
- inhibits binding of IgE to IgE receptor on the surface of mast cells and basophils
- inhibits IgE-mediated cascade of asthma
Omalizumab is give by sub-cutaneous injection every 2-3 weeks, why?
- absorbed slowly
- peak plasma concentration in 7-8days
What are the unwanted side effects of omalizumab?
- few but can be severe
- anaphylaxis - allergic reaction to protein
- malignancies (slightly higher rate than normal )
How is mild asthma with rare attacks treated?
- inhaled B2 agonist when required
How is mild asthma with more frequent attacks treated?
- glucocorticoids for prophylaxis
- B2 agonist when needed for acute attack