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45 Cards in this Set
- Front
- Back
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Both asthma and COPD are inflammatory diseases of the airways. How can you distinguish asthma from chronic obstructive pulmonary disease (COPD)? |
Asthma tends to occur in the conducting zone (upper airways) of the respiratory system. COPD happens in the terminal bronchi and alveolar sacs. |
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What are the cells that sense allergens?
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Mast cells
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How do mast cells sense allergens?
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Mast cells sense allergens due to their IGE receptors (immunoglobulins) on their surface.
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IGE dependent activation of mast cells causes the release of pro-inflammatory substances. What are the pro-inflammatory substances released? |
- Histamine - Prostaglandins - Leukotriene's -Cytokines |
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What do the pro-inflammatory substances released do?
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cause: -Bronchoconstriction -Oedema -Mucus secretion -Inflammation - involves white blood cells like eosinophils and T lymphocytes |
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What are the 2 main drugs used in the pharmacological treatment of asthma?
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1) Beta-2-agonists 2) Muscarinic antagonists (indirect; used in COPD) |
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List the anti-inflammatory agents used in the treatment of asthma... |
1) Glucocoticosteriods 2) Xanthines 3) Cromones (sodium cromoglicate, nedocromil sodium) 4) Leukotriene antagonists 5) Anti-IgE (Omalizumab) |
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Name two short acting B2 agonists (SABA) used in the treatment of asthma? SABA= short acting beta 2 agonist |
salbutamol terbutaline |
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Name two long acting B2 agonists (LABA) used in the treatment of asthma...
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sameterol formoterol |
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what is the name of the drug used in the treatment of asthma which is still undergoing development?
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Theophylline
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Beta 2 adrenoreceptor agonists are isoprenaline, salbutamol and formoterol. which ones are sub-selective (i.e act on only B1 or B2 receptors) |
isoprenaline = beta selective (B1 or B2) salbutamol = beta 2 selective formoterol = longer acting beta 2 selective (taken twice daily) |
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How do beta 2 agonists work? (in asthma treatment)
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- beta 2 agonists work by stimulating the beta 2 receptor on the epithelium in the lungs. - the G protein associated with the beta-2-adrenoreceptor activates the enzyme adenyl cyclase (which converts ATP to cAMP) -cAMP activates PKA - PKA stimulates the phosphorylation of myosin light chain kinase to its active form ---> causes relaxation of smooth muscle in the airway = reduces the effects of asthma |
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As a summary, list the different beta2-adrenoreceptor agonists
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Salbutamol terbutaline fenoterol formeterol salmetrerol indacaterol |
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what do beta 2 agonists cause? (in terms of response)
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1) smooth muscle relaxation 2) inhibits mast cell degranulation |
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beta 2 agonists elevate cyclic AMP within effector cells. true or false? |
true
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how are beta 2 agonists administered?
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administered via the inhaled route (metered dose inhaler, dry power and nebulizer)
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list the side effects of beta 2 agonists...
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1) tremor 2) increased HR 3) hypokalemia (targeting beta-receptors at extra-pulmonary sites) |
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What do effect do muscarinic antagonists have?
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prevent smooth muscle contraction prevent mucus secretion induced by activation of parasympathetic nerves |
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Bronchoconstriction is also inhibited by muscarinic antagonists. Name 2 muscarinic antagonists that inhibit bronchoconstriction... |
1) Ipratropium bromide (6 hours) 2) tiotropium bromide (24 hours) |
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what are muscarinic antagonists mainly used in the treatment of?
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COPD
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What are the side-effects of muscarinic antagonists?
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dry mouth urinary retention constipation acute angle glaucoma |
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Specifically what muscarinic receptors do muscarinic antagonists (used in the treatment of asthma) act on?
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M2 receptor (pre-junctional) M3 receptor (post-junctional) |
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What is another example of current anti-inflammatory therapy?
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Glucocorticosteriods (inhaled and oral) e.g budesonide |
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How do glucocorticosteriods work in asthma?
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1) glucocorticosteriods work by passing through the phospholipid bilayer (as they're hydrophobic) 2) glucocorticosteriods then attach to the glucocortsteriod receptor which is bound to a heat shop protein = HSP90 3) HSP90 aids the transport of the glucocorticosteriod into the nucleus of the cell. 4) HSP90 then dissociates from glucocorticoid (once in the nucleus) 5) glucocorticosteriod affects transcription in the nucleus and results in the repression of pro-inflammatory mediators and activates the transcription of inhibitiory inflammatory mediators.. |
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list examples of the proteins which are transcribed (trans-activated) in response to glucocorticosteriods...
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1) Annexin (Lipocortin) 2) Beta-2-adrenoreceptors 3) Mitogen kinase phosphatase-1 |
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list examples of the proteins which not are transcribed (trans-repression) in response to glucocorticosteriods...
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-usually anti-inflammatory enzymes e.g COX2, NOS -cytokines -chemokines -Adhesion molecules |
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List 4 actions of glucocotricosteriods in asthma...
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1) Inhibition of leukotriene and cytokine synthesis/release 2) Inhibit recruitment of inflammatory cells (e.g T cells, eosinophils, mast cells) recruitment 3) Anti-oedema 4) Increases beta-adrenoreceptor function (enhances bronchodilator effect of beta-2-agonists) |
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What is the role of inhaled corticosteroids (ICS) in asthma therapy?
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- prevents infiltration and activation of inflammatory cells. - reduces mucosal oedma (swelling of airway wall). - improves airflow and hence lung function. - decrease airway hyper-responsiveness. - reduce symptoms. - reduce frequency and severity of exacerbations. - improve quality of life. |
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Name an example of an inhaled glucocorticosteriod
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Fluticasone Proprionate
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What are the side effects of inhaled glucocorticosteriods?
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- oral candidiasis (fungal infection) - hoarseness, cough, voice problems |
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Name an example of a oral glucocoticosteriod...
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prednisolone
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What are the side effects of oral or prolonged high dose glucocorticosteriods?
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- growth retardation, bruising (cushings syndrome) - suppression of hypothalamic-pituitary axis - osteoporosis -water retention -diabetes -weight gain, hypertension, ocular hypertension |
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Another class of anti-inflammatory drug are Leukotriene antagonists and 5-lipoxygenase (5-LO) inhibitors Name a leukotriene antagonist and 5LO inhibitor |
1) Montelukast = leukotriene receptor antagonist 2) Zileuton = 5-LO enzyme inhibitor |
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how do leukotriene antagonists and 5-LO inhibitors work?
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- 5-LO converts Arachaidonic acid into leukotrienes. - inhibiting this enzyme stops the conversion of Arachidonic acid into leukotrienes. |
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What is the big advantage of leukotriene antagonists and 5-LO inhibitors?
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Oral bioavailability (can be given as tablets)
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What are the side-effects of anti-leukotriene drugs (leukotriene antagonists and 5-LO inhibitors)?
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rare to get side-effects headache and GI disturbance |
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Summary of leukotrienes and anti-leukotriene drugs (leukotriene antagonists and 5-LO inhibitors)...
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Leukotrienes are important mediators in the asthmatic response because they can actively cause bronchoconstriction, oedma, cellular infiltration etc. this is inhibited with Zileuton (5LO inhibitor) and Montelukast (leukotriene antagonist) and hence are used in the treatment of asthma. |
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An example of a B agonist used in the treatment of asthma is Xanthines. How do xanthines work to treat asthma? |
-Xanthines inhibit the enzyme phosphodiesterase (PDE) -inhibiting phosphodiesterase means we have more cAMP because its breakdown has been inhibited which means more PKA gets activated which results in airway smooth muscle relaxation. so PDE inhibition = more cAMP = more PKA activated = smooth muscle relaxation |
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Name 2 Xanthines used in the treatment of asthma...
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1) Theophylline 2) Aminophylline |
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What are the possible side effects of Xanthines?
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Nausea , vomiting, arrhythmias, hypokalemia, hypotension, seizures (also requires monitoring by a clinician because xanthines also have numerous drug-drug interactions with other drugs which decrease/increase plasma levels) |
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Cromones are another class of drug which reduce inflammatory cell activation and recruitment. list some features of cromones... |
1) mast cell stabilizers 2) not as effective as glucocorticosteriods 3) mediacations are used for hayfever 4) usually inhaled 5) cheap to produce |
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Name 2 cromone drugs...
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Sodium Cromoglicate Nedocromil sodium |
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What is the first biological agent used in the treatment of asthma?
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Omalizumab (Xolair)
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List some features of Omalizumab (Xolair)- the first biological agent for the treatment of asthma...
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- binds to free IgE receptor on the surface of mast cells - must be given as a subcutaneous injection - very costly -only used in moderate to severe asthmatics whose asthma is not controlled by glucocotricosteriods. |
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Revision list List all of the drugs involved in the treatment of respiratory diseases, namely asthma... |
1) salbutamol 2) salmeterol 3) Fluticasone propionate 4) Montelukast 5) Theophylline 6) Cromoglycate 7) Omalizumab 8) Ipratropium bromide 9) Tiotropium bromide |
