Treatment for Asthma Flashcards
Name the two first line drugs?
- B2 adrenergic receptor agonists
2. Glucocorticoids (steroids)
Name 5 other drug treatments available?
theophylline muscarinic receptor antagonists cromoglicate leukotriene antagonists new biologics
Explain the function of bronchodilators and types?
Dilate bronchioles and increase air flow to alveoli by relaxing the smooth muscle cells around walls of bronchioles
Types =
b2 adrenergic receptor agonists
theophylline
muscarinic receptor antagonists
leukotriene receptor antagonists
Whats the action of B2 adrenergic receptor agonists?
Direct action on b2 adrenoceptors on bronchiole smooth muscle to relax muscle They also inhibit mediator release from mast cells & monocytes may act on cilia to increase mucus clearance
Name short acting B2 adrenergic drugs?
salbutamol and terbutaline,
Max effect within 30 min, last 4-6 hours Used “as needed” to control symptoms
Name longer acting B2 adrenergic drugs?
salmeterol
They have a duration of action 12 hours, twice daily dose in patients not controlled with glucocorticoids
Mode of administration of B2 adrenergic drugs?
Inhalation target action in lung & minimise systemic effects
Side effects of B2 adrenergic drugs?
Result from absorption into systemic circulation most common is tremor
Some tolerance to b2 agonists may develop however this is prevented by glucocorticoid
What is Theophylline, how does it work?
It is a second line drug
The mechanism is still unclear however it is a phosphodiesterase (PDE) inhibitor
xanthine (constituent of coffee & tea)
Why is theophyline used?
It is used with steroid when asthma response to b2 agonist inadequate and given i.v. in acute severe asthma
What are the side effects of theophyline?
CNS: stimulant (tremor, sleep disturbance)
Cardiovascular (stimulate heart, vasodilation)
GI tract (anorexia, nausea, vomiting)
How do Muscarinic receptor antagonists work?
They have the same mechanism for each effect, blocking action of endogenous acetylcholine at muscarinic receptors
This causes the bronchial smooth muscle to relax causing bronchodilation, few muscarinic receptors activated and airways open
What is Ipratropium? How does it work? What are the side effects?
Ipratropium used in adjunct to b2 agonists and steroid when these are insufficient
max effect in 30 min, lasts 3-5 hours
taken via inhalation, its poorly absorbed into systemic circulation
Few unwanted effects other than that is Safe and well tolerated
Name Leukotriene receptor antagonists (CAST) drugs? There is only two!
- Montelucast (1x daily)
- Zafirlukast (2x daily)
main use as add on for uncontrolled, mild-moderate asthma
How do Leukotriene receptor antagonists work?
They act at cysteinyl-leukotriene receptors on bronchiole smooth muscle cells to prevent actions of LTC4, LTD4, which are bronchial spasmogens that stimulate mucus secretion
They are given orally to prevent exercise-induced and aspirin sensitive asthma the action additive with b2 agonists
Side effects of Leukotriene receptor antagonists?
Headache and GI disturbance
Name the anti-inflammatory drugs?
Glucocorticoids
Cromoglicate
Biologic agents
Name glucocorticoid drugs?
- beclometasone
- diproprionate
- budesonide
- fluticasone
- propionate
- occassionally prednisolone or hydrocortisone
Theses drugs are given via inhalation, to localise effect in the lungs
Full drug effect takes days
What is glucocorticoid mechanism of action?
Enter cells then bind to intracellular receptors in cytoplasm causing GRa, GRb receptor complex, this moves to nucleus and binds to DNA in nucleus to alter gene transcription e.g. induction of lipocortin, repression of IL-3
this results in a reduction of the production of cytokines, spasmogens (LTC4, LTD4) and leucocyte chemotaxins (LTB4, PAF) therefore reduces bronchospasm and recruitment & activation of inflammatory cells
What is the clinical use of glucocorticoid?
Given to patients requiring regular bronchodilators to control attacks. It is given via inhaled steroid, with additional agent for severe asthma
e.g. budesonide + b2 agonist or theophylline, i.v. hydrocortisone + oral prednisolone for acute exacerbations short course oral prednisolone if deterioration prolonged oral predisolone needed for a few patients
Side effects of glucocorticoid?
Adverse effects common with inhaled steroids oropharyngeal thrush & dysphonia minimised by using “spacer” devices reduce oropharyngeal drug deposition increase airways drug deposition
Oral/ regular large doses – serious effects e.g. adrenal suppression patients carry ‘steroid card
Name Cromoglicate drug and state its actions?
Nedocromil sodium = Can reduce both early and late phase responses Reduce bronchial hyper-reactivity
Action = not fully understood, Mast cell stabiliser (but not main action)may reduce neuronal reflexes (desensitise to irritants) inhibit release of T-cell cytokines affect inflammatory cells and mediators
Its given via inhaler
When is Cromoglicate effective?
- Effective in asthma caused by antigen, exercise, irritants Not all asthmatics respond unpredictable children respond better than adults
- Prophylactic use to prevent both phases of attack most effective in children effects may take weeks to develop
Cromoglicate side effects?
Irritation of upper respiratory tract and hypersensitivity reactions reported, but rare
Biologic agents
Omalizumab (Xolair)
recombinant DNA-derived humanized IgG1 monoclonal antibody
Given via sub cutaneous injection every 2-3 weeks absorbed slowly peak plasma concentration in 7-8 days
What is the action of Biologic agents?
- binds to human IgE
- inhibits binding of IgE to IgE receptor (Fc RI) on the surface of mast cells and basophils
- inhibits IgE-mediated cascade of asthma
Side effects of Biologic agents?
- Few, but can be severe anaphylaxis – allergic reaction to protein and malignancies (slightly higher rate than normal)
What treatment is given to a mild asthmatic with rare attacks?
inhaled b2 agonist when required
What treatment is given to a mild asthma with more frequent attacks?
glucocorticoid for prophylaxisand b2 agonist when needed for acute attack
What treatment is given to a patient with moderate to severe asthma?
drug combination preferred, usually and b2 agonist with glucocorticoid in combined inhaler
Other drugs added when this approach fails to control attacks
