Bronchial asthma (VK)

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Bronchial asthma (VK)

  1. 1. PHARMACOLOGICAL BASIS OF TREATMENT OF BRONCHIAL ASTHMA
  2. 2. Asthma - Greek word meaning “to stay awake in order to breath” or “difficulty in breathing”  Asthma is a chronic inflammatory disorder of the airways. 
  3. 3.  Chronically inflamed airways are hyper responsive; they become obstructed and airflow is limited by : 1. Broncho-constriction 2. Mucus plugs 3. Increased inflammation when airways are exposed to various risk factors.
  4. 4.  Asthma is a chronic inflammatory disease in which the patient suffers with reversible episodes of airways obstruction due to bronchial hyper-responsiveness.
  5. 5. Predisposing factors: Heredity  Age: Pediatric group most affected  Sex: within 10 years of age male: female ratio(2:1) and equal in adults.  Allergens – Food, Inhalants, Bacteria . 
  6. 6. Respiratory infections, pharmacologic stimulants occupational factors, exercise, climatic factors, low socioeconomic status.  Passive smoking.  Air pollution.  Obesity. 
  7. 7. Triggering Factors  Domestic dust mites  Air pollution  Tobacco smoke  Occupational irritants  Cockroach  Animal with fur  Pollen
  8. 8.  Asthma affects 8% in adults and 10% in children.  Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where much of the data have been collected.  The prevalence rate of severe asthma in industrialized countries ranges from 2-10%
  9. 9. Pathophysiology IgE-Antigen Complex SALBUTAMO L Eosinophi l Activation β2 Bronchodilitation AT P AC cAMP THEOPHYLLINE Chemical mediators Histamine, LTC4, LTD4, LTB4, Cytokines, Adenosine, PGD2, PAF, ECP and Neuropeptides β 2 AGONISTS Inhibit release PD E Bronchial Tone AMP Adenosine M3 cGMP CORTICOSTEROI DS NI O G Bronchoconstriction O PI U M Cause inflammation, oedema, bronchospasm, muscus secretion, epithelial damage GT P GC TR Mast Cell Degranulation AN 3 S TA Activation β 2 AGONISTS IP M RA Basophil Bronchial Smooth Muscle
  10. 10. IgE-Antigen Complex Eosinophi l Basophil Activation Bronchodilitation Activation Mast Cell Degranulation NITRIC OXIDE DONORS SOD. CROMOGLYCATE Bronchial Tone Stabilises Mast Cells Chemical mediators Histamine, LTC4, LTD4, LTB4, Cytokines, Adenosine, PGD2, PAF, ECP and Neuropeptides Leukotrienes LT-ANTAGONIST Cause inflammation, oedema, bronchospasm, muscus secretion, epithelial damage INFECTION Bronchoconstriction CORTICOSTEROI DS Bronchial Smooth Muscle
  11. 11. NEURAL CONTROL PARASYMPATHETIC + Adenosine Unmyelinated Sensory C fiber SO2, Cigarette Smoke Acetylcholine A3 Mast Cell + + A2 M3 Bronchial Smooth Muscle β2 + Neuropeptides NO Circulating Catecholamines SYMPATHETIC Neurokinin A Substance P Mediators N A N C
  12. 12. ASTHMA MANIFESTS AS 1. Breathlessness and 2. Cough 3. Recurrent episodes of wheezing 4. Chest tightness
  13. 13.  Goals of asthma therapy › To prevent chronic and troublesome symptoms › To maintain near normal pulmonary function › To maintain normal activity levels (including exercise and other physical activity) › To prevent recurrent exacerbations of asthma and minimise the need for emergency department visits to hospitalizations
  14. 14. › To provide optimal pharmacotherapy with minimal or no adverse effects › To meet pts & families expectations and satisfaction with asthma care.
  15. 15. Drugs used in Bronchial Asthma Bronchodilators Selective β2- Agonists Short acting  Salbutamol  Terbutaline  Remiterol  Fenoterol 1. Long-acting  Salmeterol,  Formoterol,  Bambuterol. 2. Non-selective Sympathomimetics  Adrenaline  Ephedrine,  Isoprenaline,  Orciprenaline, (Metaproterenol).  Isoetharine.
  16. 16. 3. Anticholinergics - Ipratropium, Tiotropium, Oxitropium, 4. Methyl Xanthines- Theophylline, Aminophylline, Diprophylline, choline theophyllinate. Anti inflammatory drugs. Corticosteroids 1. Oral: Prednisolone, Methylprednisolone, 2. Parenteral: Mehtyl Prednisolone, Hydrocorticsone 3. Inhalational: Beclomethasone, fluticasone, Triamcinolone, Budesonide, Flunisolide
  17. 17.  Mast Cell Stabilisers Sodium Cromoglvcate, Nedocromil, Ketotifen,  Leukotriene Modulators: 1. 5-Lipoxygenase inhibitor: Zileuton 2. LT-rceptor Antagonists: Zafirlukast, Montelukast, Iralukast, Pranlukast,  Monoclonal Anti-lgE Antibody omalizumab
  18. 18. 1. β2-Selective adrenoceptor agonist most widely used sympathomimetics for the treatment of asthma at the present time. 1. Short acting:- albuterol-Terbutaline used only for acute attack of bronchospasm 1. Long acting:- salmeterol –formeterol used for only prophlaxis and not for acute attack of bronchospasm.
  19. 19. Selective β2 receptor agonist mechanism of action Stimulation of β2-receptors Bronchial smooth muscle relaxation Intracellular cAMP
  20. 20. Selectively β2 receptor agonist Route of administration: Usually delivered via a metered dose inhaler with immediate effect  Orally used in children.  i.v used for acute attack.  S.C. (terbutaline) 2. Adverse effect:  Cardiac arrhythmias (at high dose has β1 effects)  Tolerance to β agonist (tachyphylaxis)  Skeletal muscle tremors. 1. 
  21. 21. Non-selective Sympathomimetics Adrenaline/epinephrine: Adrenaline/epinephrine  Agonist of α and β receptor  Adverse effect of cardiovascular system usually occurs thereby less usable  S.C. injection Ephedrine:  Orally administered  Similar action to Adrenaline  Less usable for central excitation
  22. 22. Mechanism of Action: It stimulates the β2 receptors and cause bronchodilation. Rout of administration:  As aerosol Adverse effects:  Tachycardia,  Hypertension  Worsening of angina and even arrhythmias
  23. 23. They are divided into two types:  1. Salt complex: increased water solubility without augmentation of pharmacological action, such as: aminophylline.  2. Slow-release form: small fluctuation of blood concentration after oral administration thus used for nocturnal attack of asthma.
  24. 24. Theophylline Mechanism of action  Inhibit activity of PDE cAMP bronchial relaxation cAMP PDE AMP 3. Inhibition of the cell surface receptor of adenosine
  25. 25. Theophylline 1. Route of administration:  Orally  Metabolised by P450 enzyme system 2. Pharmacodynamics  Direct positive chronotropic and inotropic effects on the heart.  In large dose, these agents also relax vascular smooth muscle.
  26. 26. Theophylline: Adverse effect  It has a narrow therapeutic index  Its therapeutic and toxic effects are related to its plasma concentration.  <20mg/L: nausea, vomiting, headache, anxiety, abdominal discomfort.  20-40mg/L: arrhythmia
  27. 27. Muscarinic antagonist 1. Mechanism:  Act by competitive blocking of muscarinic receptors (M3 subtype) 2. Route of administration:  Metered dose inhaler e.g Ipratropium bromide 3. indication:  Used as adjuncts to β2-adrenoceptor agonist in treatment of asthma.
  28. 28. Anti-inflammatory drug Glucocorticoids  Mechanism: 1. Depress the inflammatory response in bronchial mucosa thus diminish bronchial hyperresponsiveness. 2. Anti-inflammatory effect (inhibit phospholypaseA2) 3. Immunosuppressive effect.
  29. 29. Glucocorticoids Route of administration 1. Metered dose inhaler: (deeply & slowly inhale) Beclomethasone, dexamethasone 2. Intravenous used for: severe asthma status asthmaticus (prednisolone or hydrocortisone) 3. oral
  30. 30. Monoclonal anti IgE antibody Omalizumab Mechanism of action:  It prevents the binding of IgE to mast cell & thus prevents mast cell degranulation Rout of administration:  i.v or s.c Side effects:  Redness, stinging, itching, induration.
  31. 31. 1. NSAIDS like aspirin,ibuprofen,diclofenac etc. (paracetamol can be used) 2. Beta-adrenergic blockers 3. Cholinergic agents.
  32. 32. 1. Mild episodic asthma Inhaled short-acting beta2 agonist at onset of each episode (step-1) 2. Seasonal asthma start regular inhaled cromoglycate/low dose inhaled steroid(200-400micro g/day) 3-4 wks before anticipated seasonal attacks continue till 3-4 wks after the season is over treat individual episodes with inhaled short acting β2 agonist.
  33. 33. 3. Mild chronic asthma with occasional exacerbations: regular inhaled cromoglycate, episodic-short acting β2 agonist(step-2) 4. Moderate asthma with frequent exacerbations: increases doses of steroid (up to 800μg/day) +inhaled long acting β2 agonist(step-3)
  34. 34. 5. Severe asthma: Regular high dose inhaled (steroids 800-2000μg/day) though a large volume spacer device + inhaled longacting β2 agonist (salmeterol) twice daily .
  35. 35. 6. Status asthmaticus  Any pt of asthma has the potential to develop acute severe asthma which may be life Threatening.  upper respiratory tract infection is the most common precipitant.
  36. 36. Management of status asthmaticus  Hydrocortisone hemisuccinate 100mg I.V stat followed by 100-200mg 4-8 hourly infusion  Nebulized salbutamol (2.5-5mg)+ipratropium bromide (0.5mg) intermittent inhalations driven by 02.
  37. 37.  High flow humidified oxygen inhalation.  Salbutamol/terbutaline 0.4mg i.m/s.c may be added, since inhaled drug may not reach smaller bronchi due to severe narrowing/plugging.  Intubation & mechanical ventilation, if needed.
  38. 38.  Treat chest infection with intensive antibiotic therapy.  Correct dehydration and acidosis with saline+sod. bicarbonate/lactate infusion.
  39. 39. Aerosol Delivery of Drugs  High local concentration in bronchioles  Low systemic side effect.  Increased bioavailability.  Optimal particle size for deposition in airways – 1to 5μm small
  40. 40.  Four classes of antiasthma drugs, i.e β2 agonists, anti-cholinergics, cromoglycate and Glucocorticoids are available for inhalational use.  They are aimed at delivering the drug to the site of action so that lower dose is needed and systemic side effects are minimized.  Most asthma patients are now maintained on inhaled medication only.
  41. 41. Aerosol Delivery Devices: Liquid aerosols  Metered dose inhaler (MDI)  Nebulizer Powdered drugs  Dry powder inhaler (DPI), Spinhaler, Rotahaler
  42. 42. Pressurized Metered Dose Inhaler (pMDI)  In pMDI drug is dissolved or suspended in propellant under pressure and when actuated releases a predetermined dose.  Pressurized MDI can be used with spacer or without spacer.  User of spacer improves drug deposition in lungs and reduces oropharyngeal drug deposition.  Use of spacer reduces oropharyngeal drug deposition by 10-15 folds when compared to pMDI alone.
  43. 43.  Spacer acts as reservoir for drug from which patients can breathe easily.  Depending on patient’s technique, drug delivery varies from 7 to 20%.  An oropharyngeal drug deposition is about 80% with pMDI.
  44. 44.  The particle size distribution through HFA was 1.07 micrometer and that of with CFC is 3.36 micrometer.  Lung deposition of drug with HFA is 50% while with CFC it is 10-20%.  With HFA the oropharyngeal deposition is 30% whereas with CFC it is 90-94%.
  45. 45.  Spacer/holding chamber  Slow (3-5 secs) inhalation or tidal breathing immediately following actuation  Easier to use than MDI alone  Recommended for anyone using MDI Spacer
  46. 46. Nebulizers  Nebulizer convert a liquid solution or suspension into an aerosol using either a jet or ultrasonic energy.  Aerosol is then delivered to the patient through either a face mask or a mouthpiece.
  47. 47.  Nebulzer requires least patient cooperation and coordination.  Nebulzers are preferred in patients who are unable to use other devices or in acute attacks when inspiratory flow is limited.
  48. 48.  Only about 13% of the dose used is deposited in the lungs.  The doses used in nebulizers are higher than those used in other aerosol devices.  Therefore patients will receive 10-20 times the dose received from a MDI.
  49. 49. Dry Powder Inhaler (DPI)  In PDI drug is provided as micronized particles in large aggregates with or without carrier substances.  Drug delivery in DPI depends on patient’s inspiratory effort to disperse the drug and deliver it to the lungs.  Drugs deposition in lungs with DPI is 15-40% with considerable inter device variability and drug deposition in oropharynx is <60%.  DPI dose not require propellants and hand breath coordination
  50. 50. › Rapid (1-2 secs), deep inhalation; dose lost if client exhales through device › Population: > 4-5 years Rotahaler
  51. 51. Spinhaler 1. Hold spinhaler upright with mouthpiece downwards, and unscrew body 2. Put coloured end of spincap into cup of propeller, making sure it spins freely 3. Screw the two parts together and hold horizontal. Move grey sleeve up and down
  52. 52. once or twice, this will pierce capsule 4. Breathe out gently, tilt head back, put spinhaler into mouth so lips touch flange and breathe in quickly and deeply 5. Remove spinhaler from mouth and hold breath for about 10 seconds, then breathe out slowly 6. If any powder is left in spincap, repeat steps 4 and 5 until it is empty Always Demonstrate To The Patient How To Use The Spinhaler
  53. 53. Route of Administration & Dose Drug 1. Selective β2 Agonists  Salbutamol  Formoterol  Salmeterol  Terbutaline Route & Dose Inhalant: 90 μg/puff aerosol; 0.83, 0.5% solution for nebulized Oral: 2,4 mg tab; 2mg/5ml syrup. Inhalant: 12 μg/puff aerosol. 12mg/unit inhalant powder. Inhalant aerosol: 25 μg salmeterol base/puff in 60 & 120 dose containers inhalant powder 50 μg/ unit Inhalant: 0.2mg/puff aerosol. Oral: 2.5, 5 mg tab.
  54. 54. Cont…. 2. Selective Sympathomimetics  Ephedrine  Epinephrine 3. Anti-cholinergics  Ipratropium. Oral: 25mg capsules Parenteral: 25,50mg/ml/ injection Inhalant: 0.1,1, 2.25% for nebulization Parenteral: 1:10000 (0.1mg/ml) Aerosol: 18mg/μg/puff in 200 metereddose inhaler. 4. Methyl xanthenes  Aminophylline Oral: 105mg/5ml liquid, 100, 200mg tablet 5. Leukotriene Inhibitors  Montelukast  Zafirlukast  Zileuton Oral: 10 mg tablets, chewable tablets Oral: 20 mg tablets Oral: 600 mg tablets
  55. 55. Cont… 6. Corticosteroids  Beclomethasone Budesonide  Dexamethasone  Aerosol Powder: 42 μg/puff in 200 dose container Aerosol Powder: 160 μg/activation Aerosol powder: 84 μg/puff in 170 dose container 7. Mast cell stabilisers Pulmonary aerosol: 800 μg/puff in 200 dose  Cromolyn sodium container; 20mg/2ml for nebulization.  Nedocromil sodium Pulmonary aerosol: 1.75 mg/puff in 113 metered-dose container.
  56. 56.  Asthma cannot be cured but can be controlled with regular use of medications.  Asthma is treated with two types of medicines:  Long term control  Quick-relief medicines
  57. 57.  Long term control medicines help to reduce airway inflammation and prevent asthma symptoms.  Quick-relief,or “rescue", medicines relieve asthma symptoms that may flare up.  Initial asthma treatment will depend on severity of the disease.
  58. 58.  Patient counseling on drug therapy should concentrate on drugs used to relieve symptoms, drugs used to prevent asthma attacks and those drugs which are given only as reverse treatment for severe attacks.

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