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Asthma medications

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Asthma medications

  1. 1. 2 Asthma medicationsAsthma medications
  2. 2. 3
  3. 3. Asthma, irrespective of the severity, is a chronic inflammatory disorder of the airways. Airway inflammation is associated with: ● Airway hyperresponsiveness ● Airflow limitation ● Respiratory symptoms. Definition of AsthmaDefinition of Asthma
  4. 4. Airway inflammation Airflow obstruction Bronchial hyperresponsiveness SymptomsSymptoms Asthma Pathophysiology The tip of the iceberg Source: Peter J. Barnes, MDSource: Peter J. Barnes, MD
  5. 5. 6 o …… in susceptible individuals, inflammatory symptoms are usually associated with widespread but variable airflow obstruction and an increase in airway response to a variety of stimuli. o Obstruction is often reversible, either spontaneously or with treatment. Asthma definition
  6. 6. Airway inflammation Airflow obstruction Bronchial hyperresponsiveness SymptomsSymptoms Asthma Pathophysiology The tip of the iceberg
  7. 7. 8 • Inflammation in asthma patients can be present during symptom-free periods: o Symptoms resolve quickly. Inflammation, however, as measured by airway hyperresponsiveness, takes far longer time . o As chronic inflammation causes an increase in airway hyperresponsiveness, if the inflammation is not controlled, symptoms are likely to reoccur.
  8. 8. 9 Can asthma be cured? Asthma is an eminently controllable illness. Indeed, for most sufferers, control is so effective that it amounts to a virtual cure. But asthma is not curable  Asthma is a long-term disease that has no cure. The goal of asthma treatment is to control the disease.
  9. 9. 10 Aim of management Aim of asthma management is to control the disease Complete Control is defined as 1. No daytime symptoms 2. No night-time awakening due to asthma 3. No need for rescue medication 4. No asthma attacks 5. No limitations on activity including exercise 6. Normal lung function (in practical terms FEV1 and/or PEF>80% predicted or best) 7. Minimal side effects from medication.
  10. 10. 11 Underlying principles of management •Before initiating drug treatment check – Compliance with existing treatment – Inhaler technique – Eliminate trigger factors
  11. 11. 12 Pharmacological management
  12. 12. 14 Smooth muscle dysfunction Airway inflammation/ remodelling r • Inflammatory cell infiltration/ activation • Mucosal oedema • Cellular proliferation • Epithelial damage • Basement-membrane thickening • Bronchoconstriction • Bronchial hyper-reactivity • Hyperplasia • Inflammatory-mediator release Symptomsexacerbations Asthma is a two component disease
  13. 13. (ICS)
  14. 14. 16 Inhaled therapy constitutes the cornerstone of asthma treatment .
  15. 15. 17 Not all asthma inhalers are the same
  16. 16. 18
  17. 17. 19
  18. 18. 20
  19. 19. 21 Controllers  Inhaled corticosteroids  Inhaled long-acting b2- agonists  leukotrienes modifiers  Sustained release theophylline  Systemic glucocorticosteroids  Anti-IgE (Omalizumab) Relievers  Inhaled short acting b2-agonists  Short acting anticholinergics  Methylxanthines Medications for Asthma Management
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  21. 21. 23
  22. 22. 24 • The following medicines act as short-acting bronchodilators:  Inhaled short-acting β 2 agonists  Inhaled ipratropium bromide  β 2 agonist tablets or syrup  Theophyllines. • Inhaled SABA works more quickly and/or with fewer side effects than the alternatives
  23. 23. 25
  24. 24. 26 • Prescribe an inhaled short-acting β2 agonist as short term reliever therapy for all patients with symptomatic asthma.
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  28. 28. 30  Salbutamol is the commonly used inhaled bronchodilator therapy .  It is a short- acting ß-2 agonist, has a rapid onset of action (within five minutes) and usually provides 4–6 hours of bronchodilation.  It should be used as a reliever therapy and is in the first step of all guidelines on asthma management.
  29. 29. 31 The use of short-acting inhaled beta2-agonists on a daily basis, or increasing use, indicates the need for additional long term control therapy.
  30. 30. 32 Rescue Medications
  31. 31. 33  Oral preparations of beta2 agonists have been used extensively in the past with children but are less effective than inhaled preparations and have more side-effects
  32. 32. 34 The use of albuterol syrup has fallen out of favor over the past decade with the advent of better modalities of targeted, inhaled delivery systems (e.g., MDI with spacer/holding chamber, nebulizer solution). • AAAAI Guidelines (2004, p88) prefer inhaled beta2-agonists to oral because higher concentrations are delivered more effectively to the airways, the onset of action is substantially shorter, and systemic side effects can be avoided or minimized. • Authors concluded lack of updated information was a possible reason that community-based PCPs continued to prescribe syrup. Special Consideration – Albuterol Syrup
  33. 33. 35  It is important that while reviewing a patient with asthma, the practitioner establishes how often the patient needs the reliever therapy.  Need for frequent bronchodilator therapy, especially for interval symptoms such as exercise intolerance or night coughs, may indicate escalation of therapy .
  34. 34. 36  Increasing use of SABA treatment or the use of SABA > 3 doses a week for symptom relief (not prevention of EIB) generally indicates inadequate asthma control and the need for initiating or intensifying anti-inflammatory therapy.  Regularly scheduled, daily, chronic use of SABA is not recommended.
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  36. 36. 38    Good asthma control is associated with little or no need for short-acting β2 agonist.  Anyone prescribed more than one short acting bronchodilator inhaler device a month should be identified and have their asthma assessed urgently and measures taken to improve asthma control if this is poor.
  37. 37. 39
  38. 38. Beclomethasone Budesonide Fluticasone Inhaled corticosteroids
  39. 39. 41 • Inhaled corticosteroids are the recommended & most effective preventer drug for adults and children with asthma , for achieving overall treatment goals.
  40. 40. 42 • There is an increasing body of evidence demonstrating that, at recommended doses, ICS are also safe and effective in children under five with asthma.
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  44. 44. 46 Beclomethasone Dipropionate  100 ug/dose Beclomethasone Dipropionate   50 ug/dose
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  50. 50. 52  In adults, a reasonable starting dose of inhaled corticosteroids will usually be 400 micrograms BDP per day and in children 200 micrograms BDP per day.  Titrate the dose of inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained
  51. 51. 53 Is important that while considering a change of the type of steroids or inhaler device used (e.g. Turbohaler), equivalent doses of inhaled steroids relative to beclometasone are given before the change is initiated to avoid any inadvertent risk of overdosing with steroids.
  52. 52. 54  BDP and Budesonide are approximately equivalent in clinical practice, although there may be variations with different delivery devices.  At present a 1:1 ratio should be assumed when changing between BDP and budesonide.  Fluticasone provides equal clinical activity to BDP& budesonide at half the dosage  Mometasone appears to provide equal clinical activity to BDP and budesonide at half the dosage.   COMPARISON OF INHALED CORTICOSTEROIDS
  53. 53. 55  Most current ICS are slightly more effective when taken twice rather than once daily, but may be used once daily in some patients with milder disease.  There is little evidence of benefit for dosage frequency more than twice daily.   Give inhaled corticosteroids initially twice daily (except ciclesonide which is given once daily). Frequency of dosing of inhaled corticosteroids
  54. 54. 56 ICS usage as a preventer therapy should be explained to the parents in simple, plain terms.
  55. 55. 57 Pharmacokinetics of Inhaled Drugs
  56. 56. Children’s Healthcare of Atlanta Dose, drug, &Dose, drug, & route dependentroute dependent Corticosteroids for Asthma: Benefits and Risks ReducesReduces inflammationinflammation Most effectiveMost effective long-term controllong-term control medication formedication for asthma*asthma* DecreasesDecreases morbidity / mortalitymorbidity / mortality Generally knownGenerally known and can beand can be monitoredmonitored BenefitsBenefits RisksRisks
  57. 57. 59  The safety of ICS is of crucial importance and a balance between benefits and risks for each individual needs to be assessed.  Account should be taken of other topical steroid therapy (e.g. for eczema) when assessing systemic risk  Steroid warning cards should be issued to patients on higher dose inhaled steroids, and at every review,signs of systemic steroid toxicity should be actively looked for .  
  58. 58. 60  Administration of medium or high dose ICS (at or above 400 micrograms BDP a day or equivalent) may be associated with systemic side effects(e.g growth failure and adrenal suppression) .  Isolated growth failure is not a reliable indicator of adrenal suppression and monitoring growth cannot be used as a screening test of adrenal function .
  59. 59. 61  Monitor growth (height and weight centile) of children with asthma on an annual basis.  The lowest dose of inhaled corticosteroids compatible with maintaining disease control should be used.  
  60. 60. 62
  61. 61. 63 In general,while the use of ICS may be associated with adverse effects (including the potential to reduced bone mineral density) with careful ICS dose adjustment this risk is likely to be outweighed by their ability to reduce the need for multiple bursts of oral corticosteroids .   
  62. 62. 64 1. Oropharyngeal candidiasis 2. Hoarseness 3. Coughing To reduce the potential for adverse affects:  Use the lowest dose necessary to maintain control.  Administer with spacers/holding chambers.  Advise patients to (Rinse with water , gargle and spit out) after inhalation. Local side effects
  63. 63. 65
  64. 64. 66
  65. 65. 67  In children, pMDI and spacer are the preferred method of delivery of β2 agonists or inhaled corticosteroids.  A face mask is required until the child can breathe reproducibly using the spacer mouthpiece.  Where this is ineffective a nebuliser may be required    
  66. 66. 68
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  68. 68. 70
  69. 69. 71 Without Spacer With Spacer
  70. 70. 72 Aerochamber spacer Aerochamber spacer with mask
  71. 71. 73
  72. 72. Choosing an inhaler device for children with asthma * - Age group Preferred device Alternative device Younger than 4 years Pressurized metered-dose inhaler plus dedicated spacer with face mask Nebulizer with face mask 4-5 years Pressurized metered-dose inhaler plus dedicated spacer with mouthpiece Nebulizer with mouthpiece Older than 6 years Dry powder inhaler or breath actuated pressurized metered-dose inhaler or pressurized metered-dose inhaler with spacer with Nebulizer with mouthpiece
  73. 73. 75
  74. 74. 76
  75. 75. 77
  76. 76. 78  Inhaled medications is a waste of money if not used properly  Poor technique is a barrier to good control  Check at each visit  Don’t rely on patient’s knowledge – ask them to demonstrate
  77. 77. 79 Fate of inhaled drugs – Good Technique  Swallowed GI tract Deposited in lung Lungs Metabolism or absorption from the lung Liver Oral bioavailability Absorption from gut First-pass metabolism Systemic Circulation Mouth pharynx mucociliary clearance  80%  20%  Schematic representation of potential dose distribution   A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for Respiratory Care. 1st Edition. Page 1. Webpage: http://www.aarc.org/education/aerosol_devices/ Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
  78. 78. 80 Fate of inhaled drugs – Good Technique  Swallowed GI tract Deposited in lung Lungs Metabolism or absorption from the lung Liver Oral bioavailability Absorption from gut First-pass metabolism Systemic Circulation Mouth pharynx mucociliary clearance  80%  20%  Schematic representation of potential dose distribution   A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for Respiratory Care. 1st Edition. Page 1. Webpage: http://www.aarc.org/education/aerosol_devices/ Adapted from Barnes et al. AJRCCM 1998;157:S1-S53 Swallowed GI tract Deposited in lung Lungs Metabolism or absorption from the lung Liver Oral bioavailability Absorption from gut First-pass metabolism Systemic Circulation Mouth pharynx mucociliary clearance  95%  5%  Schematic representation of potential dose distribution  Adapted from Barnes et al. AJRCCM 1998;157:S1-S53 A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for Respiratory Care. 1st Edition. Page 1. Webpage: http://www.aarc.org/education/aerosol_devices/ Fate of inhaled drugs – Poor Technique 
  79. 79. 81  Stepping down therapy once asthma is controlled is recommended , but often not implemented leaving some patients overtreated.  Patients should be maintained at the lowest possible dose of inhaled corticosteroid.  Reduction in inhaled corticosteroid dose should be slow as patients deteriorate at different rates.  
  80. 80. 82 Stepping down therapy  Reductions should be considered every three months, decreasing the dose by approximately 25–50% each time.  Regular review of patients as treatment is stepped down is important .    
  81. 81. Treatment Options for adult Patients Not Controlled on Inhaled Steroids                     Patients not controlled on inhaled steroidsPatients not controlled on inhaled steroids                    Patients not controlled on inhaled steroidsPatients not controlled on inhaled steroids Increase theIncrease the dose of inhaleddose of inhaled steroidsteroid Add leukotrieneAdd leukotriene receptor receptor  antagonistsantagonists Add long-acting beta2-agonists Add Add  theophyllinetheophylline
  82. 82. 84 LABA’s
  83. 83. 85 LABA’s
  84. 84. Children’s Healthcare of Atlanta • Recent data indicating a possible increased risk of asthma Related death associated with use of LABA in a small group of individuals has resulted in increased emphasis on the message that: • LABA should not be used as monotherapy in asthma & must only be used in combination with an appropriate dose of ICS.
  85. 85. 87  Long-acting inhaled β2 agonists should only be started in patients who are already on inhaled corticosteroids, and the inhaled corticosteroid should be continued.  The benefits of these medicines used in conjunction with ICS in the control of asthma symptoms outweigh any apparent risks. SAFETY OF LONG-ACTING Β2 AGONISTS
  86. 86. 88  In clinical practice, however, it is generally considered that combination inhalers (ICS and LABA) aid adherence and also have the advantage of guaranteeing that the LABA is not taken without the ICS
  87. 87. Combination Medications Combination Medications ICS LABA Symbicort® Budesonide (Pumicort®) Formoterol (Oxeze®) Seretide® Fluticasone (Floxitide®) Salmeterol (Severent®)
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  103. 103. Children’s Healthcare of Atlanta
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  110. 110. 112 ANTI-IgE MONOCLONAL ANTIBODY  Omalizumab is a humanised monoclonal antibody which binds to circulating IgE, reducing levels of free serum IgE.  In adults and children over 6 years of age, it is licensed in the UK with the following indication: patients on high-dose ICS and long-acting β2 agonists who have impaired lung function, are symptomatic with frequent asthma attacks, and have allergy as an important cause of their asthma.
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  114. 114. 116  Omalizumab is given as a subcutaneous injection every two or four weeks depending on IgE level and weight. The total IgE must be <1,300 international units (IU)/ml for children over 6 years of age.  In adults and children >12 years, the licensed indication is a IgE up to 1,500 IU/ml but there is no published data to support its efficacy and safety above 700 IU/ml.
  115. 115. 117  Local skin reactions may occur , Anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue has been reported to occur after administration of omalizumab. Anaphylaxis has occurred as early as the first dose, but has also occurred after one year.  Due to risk of anaphylaxis, omalizumab should only be administered to patients in a healthcare setting under direct medical supervision.
  116. 116. 118  Omalizumab given by subcutaneous injection may be considered in patients with a high steroid burden to reduce the steroid burden for the patient.  Omalizumab treatment should only be initiated in specialist centres with experience of evaluation and management of patients with severe and difficult asthma.
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