Asthma Drugs Flashcards
What is the difference between acute and chronic asthma?
Chronic is recurrent attack of reversible airway obstruction of air flow - can be controlled. Acute is severe asthma that can be fatal and is not easily reversed with drugs.
What are the features of asthma?
Characterised by: inflammation in the airways and hyper-reactivity to bronchioles to: irritant chemicals, cold air and stimulant drugs. Also - bronchoconstriction and mucus secretion.
What is the aim of drug treatment in asthma?
To reduce inflammation, prevent bronchoconstriction and restore airways calibre to normal.
What are the different types of stimuli that can trigger an asthma attack?
Exercise, respiratory infection, atmospheric pollutants. Allergens such as pollen, dust mite proteins and animal dander.
How does asthma develop?
Allergen activates B cells. IgE is made and presents onto mast cell. Presentation of antigen onto mast cells causes inflammatory cell recruitment and bronchoconstriction.
What are the 2 different phases of an asthma attack?
Early phase: bronchospasm
Late phase: inflammation
What stages are involved in the early phase of attack?
Bronchial muscle contracts. Mast cells release spasmogens: histamine, leukotrienes and prostaglandin D2. Mast cells also release inflammatory mediators: interleukins 4, 5 and 13, macrophage inflammatory protein, tumour necrosis factors and chemokines.
What stages are involved in the late phase of attack?
Progressing inflammatory reaction - lymphocytes and eosinophils invade. Agents from inflammatory cells cause: damage and loss of bronchial epithelium, smooth muscle hypertrophy and hyperplasia, hyper-reactivity to irritant stimuli.
What are the actions of bronchodilators?
Dilate bronchioles and increase air flow to alveoli. Relax smooth muscle cells around walls of bronchioles.
What are the different types of bronchodilators?
B2 adrenergic receptor agonists. Theophylline. Muscarinic receptor antagonists. Leukotriene receptor antagonists.
What is the action of B2 adrenergic receptor agonists?
Direct action on B2 adrenoceptors on bronciole smooth muscle to relax muscle. Also: inhibit mediator release from mast cells and monocytes and may act on cilia to increase mucus clearance.
How are the B2 adrenoceptors activated?
B2 receptor attaches to cell membrane, ATP causes inactive protein kinase A to be activated which causes protein phosphorylation and then muscle relaxation.
What are the short acting B2 agonists called?
Salbutamol and Terbutaline. Max effect within 30 mins, lasts 4-6 hours.
What is the longer acting B2 agonist called?
Salmeterol - 12 hours.
How are B2 agonists administered?
By inhalation
What are the unwanted effects of B2 agonists?
Most common is tremor. Some tolerance may develop.
What is Theophylline?
Formed from xanthine (constituent of coffee and tea). Mechanism unclear but it is a Phosphodiesterase inhibitor (PDE).
When is Theophylline used?
Second line drug - sustained release tablet. Used with steroid when asthma response to B2 agonist inadequate. Given IV in acute severe asthma.
What are the side effects of Theophylline?
Tremor/Sleep disturbance. Stimulates heart, vasodilation. Anorexia, N&V.
What is the name of the main muscarinic receptor antagonist?
Ipratropium - lasts 3-5 hours. Given by inhalation.
What are the actions of muscarinic antagonists?
Relax bronchial smooth muscle - bronchodilation. Inhibit elevated mucus secretion. Block action of acetylchloine at muscarinic receptors.
What happens in the muscarinic system in the normal airways?
Low levels of Ach released from cholinergic nerves in the airways: few muscarinic receptors activated, smooth muscle relaxed, airways open.
What happens in the muscarinic system in ASTHMA?
Evidence for increased Ach release: muscarinic receptors activated, smooth muscle contracted, narrowed airways.
What are the 2 types of Leukotriene receptor antagonists?
Montelucast
Zafirlukast
Why are leukotriene antagonists prescribed?
Prevent exercise-induced a d aspirin sensitive asthma. Action additive with B2 agonists. Main use as add on for uncontrolled, mild-moderate asthma.
What do leukotrienes do?
Cause bronchoconstriction and increase vascular permeability.
What are the actions of leukotriene antagonists?
Act at leukotriene receptors on bronchial smooth muscle cells. Prevent actions of LTC4 and LTD4 (these are bronchial spasmogens and stimulate mucus secretion).
What are the side effects of leukotriene antagonists?
Headache and GI disturbance.
What are the main type of anti-inflammatory drugs used in asthma?
Glucocorticoids - beclometasone, budeonside, fluticasone propionate, prednisolone or hydrocortisone.
What are the actions of glucocorticoids?
Reduce production of cytokines, spasmogens and leucocyte chemotaxins. Therefore reduce bronchospasm and recruitment of inflammatory cells.
What is the mechanism of glucocorticoid action?
Enter cells, bind to intracellular receptors in cytoplasm, receptor complex moves to nucleus, binds to DNA in nucleus, alters gene transcription.
What are the side effects of glucocorticoids?
Oral thrush and dysphonia. serious - adrenal suppression.
What does cromoglicate do?
Can reduce both early and late phase responses. Reduces bronchial hyper-reactivity. Effective in asthma caused bu antigens and irritants.
What is the mechanism of cromoglicate?
Mast cell stabiliser may reduce neuronal reflexes, inhibit release of T cell cytokines, affect inflammatory cells.
What are the side effects of cromoglicate?
Irritation of upper resp tract. Hypersensitivity reactions supported.
What is the main biologic agent used in asthma?
Omalizumab - monoclonal antibody. S/C injection every 2-3 weeks.
What is the mechanism of Omalizumab?
Binds to human IgE and inhibits binding of IgE to IgE receptor on the surface of mast cells. This stops bronchoconstriction.
What are the side effects of omalizumab?
Anaphylaxis and rare malignancies.
What is prescribed for a person with mild asthma and rare attacks?
Inhaled B2 agonist when required.
What is prescribed for a person with mild asthma and more frequent attacks?
Glucocorticoid and B2 agonist.
What is prescribed for a person with moderate to severe asthma?
Drug combination preferred: B2 agonist with glucocorticoid in combined inhaler.
