Pharmacotherapy of Asthmatic patient in hospital
- 2. Chapter Outline 1. Asthma 2. Chronic Obstructive Pulmonary Disease (COPD) 3. ARDs & Neonatal Respiratory distress syndrome 4. Drug-induced pulmonary diseases 2
- 4. Learning Objectives….After completion…. 4 Explain the pathophysiology of asthma Identify the goals of asthma management. Classify asthma severity based on asthma symptoms. Recommend environmental control strategies for patients with identified allergies. Educate patients on the use of inhaled drug delivery devices, peak flow monitors, and asthma education plans. Develop a therapeutic plan for patients with chronic asthma that maximizes patient response while minimizing adverse drug events and other drug-related problems. Develop a therapeutic plan for treating patients with acute asthma.
- 5. Asthma: Introduction 5 Asthma is a chronic inflammatory disorder of the airways, involving airway hyperresponsiveness that leads to widespread and variable episodes of reversible airway obstruction This airway obstruction results in wheezing, breathlessness, chest tightness, and coughing, particularly at night or early in the morning Severity of chronic disease ranges from mild intermittent symptoms to a severe and disabling disease if left untreated Asthma is the most prevalent chronic disease of childhood, and it causes significant morbidity and mortality in both adults and children
- 6. Asthma: Etiology 6 Underlying cause is not well understood Results from a complex interaction of genetic & environmental factors The presence of asthma in a parent is a strong risk factor for development of asthma in a child/early onset asthma This risk increases when a family history of atopy is also present Patients with occupational asthma develop the disease late in life upon exposure to specific allergens in the workplace/late onset asthma
- 7. Asthma Triggers Respiratory infection RSV, rhinovirus, influenza, parainfluenza, Mycoplasma pneumonia Allergens Airborne pollens (grass, trees, weeds), house-dust mites, animal danders, cockroaches, fungal spores Environment Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco smoke, wood smoke Emotions Anxiety, stress, laughter Exercise Particularly in cold, dry environments Drugs / preservatives Aspirin, NSAIDs (cyclooxygenase inhibitors), sulfites, benzalkonium chloride, nonselective β-blockers Occupational stimuli Bakers (flour dust); farmers (hay mold); spice and enzyme workers; printers (arabic gum); chemical workers (azo dyes, anthraquinone, ethylenediamine, toluene diisocyanates, polyvinyl chloride); plastics, rubber, and wood workers (formaldehyde, western cedar, dimethylethanolamine, anhydrides) 7
- 8. Asthma: Pathophysiology 8 The underlying problem is intense airways inflammation, airway hyperresponsiveness and airway obstruction Individuals with asthma appear to produce large amounts of the antibody IgE that attach to the mast cells present in many tissues. Exposure to a trigger such as pollen will result in the allergen-binding mast cell-bound IgE, which in turn causes the release of inflammatory mediators such as histamine, leukotrienes and eosinophilic chemotactic factor Disease Pattern: Episodic(acute exacerbations interspersed with symptom- free periods)
- 9. • Cellular proliferation • Smooth muscle cell • Mucosa Glands •Basement membrane thickening •Angiogenesis •Increased matrix deposition •Increased inflamm cell number •Mucosal edema •BHR •Air way secretions •Epithelial damage
- 10. Risk factors for a fatal asthma attack Previous severe exacerbation (eg, intubation or ICU admission) 2 hospitalizations for asthma in the past year 3 emergency department visits for asthma in the past year Hospitalization or emergency department visit for asthma in the past month Use of >2 canisters of short-acting beta agonist per month Difficulty perceiving asthma symptoms or severity of exacerbations Low socioeconomic status, inner city residence, illicit drug use, major psychosocial problems
- 11. Asthma: Clinical Presentation and Diagnosis 11 Symptoms Wheezing, SOB, coughing (usually worse at night), and chest tightness Patients may be anxious and agitated In acute severe asthma, pts may be unable to communicate in complete sentences Mental status changes may indicate impending respiratory failure Symptoms usually have a pattern Signs Tachypnea and tachycardia On inspection, there may be hyperexpansion of the thorax and use of accessory muscles Auscultation of the lungs may detect wheezes Bradycardia and absence of wheezing may indicate impending respiratory failure
- 12. Asthma: Clinical Presentation and Diagnosis 12 Laboratory tests Spirometry demonstrates reversible airway obstruction with an FEV/FVC less than 80% and either an: increase in FEV1 of 12% or 200 mL after receiving a bronchodilator, or increase of 10% in the predicted FEV1 after receiving a bronchodilator. Elevated immunoglobulin E(IgE) levels may be present. Some pts will have positive skin test or radioallergosorbent test (RAST) to allergens ABGs : in pts with severe distress, or PEF or FEV1 is <30% after initial treatment CBC: in pts with fever or purulent sputum A chest x-ray should be performed when pneumonia is suspected.
- 13. Asthma: Chronic Asthma 13 Chronic asthma is classified as either: intermittent or persistent asthma that may be categorized as mild, moderate, or severe The assessment of severity is similar in older patients. However, in patients 12 years of age and older, it is recommended to initiate treatment in severe persistent asthma at step 4 or 5 (instead of step 3 in children younger than 12 years) Initial classification of asthma severity is based on current disease impairment and future risk
- 14. Asthma: Chronic Asthma 14 Impairment refers to the frequency and severity of symptoms, use of short- acting β2-agonists (SABA) for quick relief of symptoms, pulmonary function, and impact on normal activity and quality of life. Risk refers to the potential for future severe exacerbations and asthma- related death, progressive loss of lung function (adults) or reduced lung growth (children), and the occurrence of drug-related adverse effects.
- 15. Classifying Asthma Severity for Patients Not Currently Taking Long-Term Control Medications (0-11 years old) 15 Components Intermittent Persistent Mild Moderate Severe Impairment Symptoms ≤2 days/week >2 days/week but not daily Daily Throughout the day Nighttime awakenings (0-4 yr) None 1-2 times/month 2-3 times/month > Once a week Nighttime awakenings (5-11 yr) ≤twice/month 3-4 times/month > Once per week but not nightly Often 7 times/week SABA use for symptom control ≤2 days/week >2 days/week but not daily Daily Several times per day Interference with normal activity None Minor limitation Some limitation Extremely limited Lung function (5-11 yr) FEV1 >80% FEV1/FVC >85% FEV1 >80% FEV1/FVC >80% FEV1 60-80% FEV1/FVC 75-80% FEV1 <60% FEV1/FVC <75% Risk Exacerbations Intermittent Persistent (0-4 yr) 0-1/year ≥2 in 6 months or ≥4 wheezing episodes/1 yr lasting >1 day (5-11 yr) 0-2/year >2 in 1 year Recommended step for initiating treatment Step 1 Step 2 Step 3 and consider short course of systemic oral corticosteroids Normal FEV1/FVC: ages 8–19 = 85%; ages 20–39 = 80%; ages 40–59 =
- 16. Asthma: Acute Asthma 16 Severity at the time of the evaluation can be estimated by Signs and symptoms or presenting peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) The exacerbation is considered Mild: dyspnea with activity and PEF is at least 70% of the personal best value Moderate: dyspnea limits activity and PEF is 40% to 69% of the personal best Severe: PEF <40% and dyspnea interferes with conversation or occurs at rest Life-threatening: When pt is not able to speak and personal best PEF is less than 25% of the personal best predicted value
- 17. Chronic Asthma: Goal of Therapy 17 Reduce impairment prevent chronic and troublesome symptoms require infrequent use (≤ 2 days a week) of inhaled SABA for quick relief of symptoms maintain (near-) normal pulmonary function maintain normal activity levels meet patients’ and families’ expectations of satisfaction with asthma care Reduce risk prevent recurrent exacerbations minimize need for visits/hospitalizations prevent loss of lung function prevent reduced lung growth in children minimal adverse effects of therapy
- 18. Acute Asthma: Treatment 18 Treatment goals are to: correct significant hypoxemia reverse airflow obstruction rapidly, and reduce the likelihood of exacerbation relapse or recurrence of severe airflow obstruction in the future
- 19. Asthma: Nonpharmacologic Treatment 19 Environmental control Manage comorbid conditions Self-management skills written action plans recognize early signs of deterioration Education asthma, role of medications, inhalation technique, environmental control, how to use action plan reinforce every visit
- 20. Asthma: Pharmacologic Therapy 20 Long-term control medications ICS, Inhaled long-acting β2-agonists (LABAs) Oral theophylline Oral leukotriene receptor antagonists (LTRAs) Omalizumab Systemic corticosteroids (in patients with severe asthma) Quick-relief medications SABAs(Albuterol or Salbutamol) Anticholinergics(Ipratropium bromide and Tiotropium bromide) Systemic corticosteroids(Short bursts)
- 21. Drug Delivery Devices 21 Direct airway administration of asthma medications through inhalation is the most efficient route and minimizes systemic adverse effects. Inhaled asthma medications are available in metered- dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulized solutions. Selection of the appropriate inhalation device depends on patient characteristics and medication availability Appropriate inhalation technique is vital for optimal drug delivery and therapeutic effect up to 30% cannot master MDI technique Rinse mouth after inhaled corticosteroids (ICS) < 4 years old usually need to attach a face mask to the inhalation device
- 22. Steps for Using Your Inhaler 22 1. Remove the cap and hold inhaler upright 2. Shake the inhaler 3. Tilt your head back slightly and breathe out slowly 4. Position the inhaler • A or B is optimal • C is acceptable for those who have difficulty with A or B; required for breath-activated inhalers
- 23. Steps for Using Your Inhaler 23 5. Press down on the inhaler to release medication as you start to breath in slowly 6. Breathe in slowly (3 to 5 seconds) 7. Hold your breath for 10 seconds to allow the medicine to reach deeply into your lungs 8. Repeat puff as directed. Waiting 1 minute between puffs may permit second puff to penetrate your lungs better 9. Spacers/holding chambers are useful for all patients. Recommended for young children and older adults and for use with corticosteroids.
- 24. β2-Adrenergic Agonists 24 Relax airway smooth muscle Increase mucociliary clearance and stabilize mast cell membranes The early-phase response to antigen in an asthma exacerbation is blocked by pretreatment with inhaled SABAs Short-acting β2-agonists have significantly better bronchodilating activity in acute asthma than theophylline or anticholinergic agents Adverse effects of β2-agonists include tachycardia, tremor, and hypokalemia, which are usually not troublesome with inhaled dosage forms. Oral β2-agonists have increased adverse effects and are not used in the treatment of asthma.
- 25. Short-Acting Inhaled β2-Agonists 25 Inhaled SABAs are the most effective agents for reversing acute airway obstruction caused by bronchoconstriction and are the drugs of choice for treating acute asthma and symptoms of chronic asthma as well as preventing exercise-induced bronchospasm Inhaled SABAs have an onset of action of less than 5 minutes and a duration of action of 4 to 6 hours Using an MDI with a spacer is quicker and at least as effective as administration by nebulization Albuterol (known as salbutamol outside the USA), the most commonly used inhaled SABA, is available as an MDI and solution for nebulization During an asthma exacerbation, the usual SABA doses are doubled and the regimen changes from as needed
- 26. Long-Acting Inhaled β2-Agonists 26 Salmeterol and formoterol are LABAs that provide up to 12 hours of bronchodilation after a single dose. Because of the long duration of bronchodilation, these agents are useful for patients experiencing nocturnal symptoms. Salmeterol is a partial agonist with an onset of action of ≈ 30 minutes Formoterol is a full agonist that has an onset of action similar to that of albuterol, but it is not currently approved for the treatment of acute bronchospasm LABAs are indicated for chronic treatment of asthma as add-on therapy for patients not controlled on low to medium doses of ICS.
- 27. Corticosteroids 27 Most potent anti-inflammatory agents available for the treatment of asthma and are available in inhaled, oral, and injectable dosage forms They decrease airway inflammation, attenuate AHR, and minimize mucus production and secretion, improve the response to β2-agonists Only therapy shown to reduce risk of asthma death Inhaled Corticosteroids(ICS) preferred therapy for all forms of persistent asthma in all age groups more effective than LTRA and theophylline in improving lung function and preventing emergency department visits and hospitalizations due to asthma exacerbations Advantage: targeted drug delivery to the lungs, which
- 28. Systemic Corticosteroids 28 Prednisone, prednisolone, and methylprednisolone Cornerstone of treatment for acute asthma not responding to an SABA Onset of action is 4 to 12 hours The oral route is preferred in acute asthma; there is no evidence that IV corticosteroid administration is more effective. Continue full dose therapy until PEF≥ 70% of predicted or personal best and Asthma symptoms are resolved Duration of therapy usually ranges from 3 to 10 days Tapering the corticosteroid dose in patients receiving short bursts (up to 10 days) is usually not necessary because any adrenal suppression is transient and
- 29. Anticholinergics 29 Mechanism: bronchodilator by competitively inhibit muscarinic receptors produce bronchodilation but not effect on BHR Less effective bronchodilator than β2-agonists Not FDA approved for asthma Available inhaled anticholinergics Ipratropium Tiotropium: studies inconclusive for use in asthma Ipratropium bromide (Atrovent) Available as an MDI and solution for nebulization Use: adjunct when incomplete response to SABA alone Onset and duration of action: ≈30 minutes(onset) 4 to 8 hours duration/intensity of action dose dependent
- 30. Leukotriene Modifiers 30 Anti-inflammatory medications that either by Inhibiting 5-lipoxygenase: (zileuton) or Competitively antagonizing the effects of leukotriene (LTRA): zafirlukast and montelukast Although these agents offer the convenience of oral administration, they are significantly less effective than low ICS doses Use: alternative/adjunct therapy Beneficial for asthma pts with allergic rhinitis or aspirin sensitivity
- 31. Methylxanthines: Theophylline 31 Has anti-inflammatory properties and causes bronchodilation by inhibiting phosphodiesterase and antagonizing adenosine. Its use is limited because of inferior efficacy as a long-term controller medication compared with ICS, a narrow therapeutic index with potentially lifethreatening toxicity, and multiple clinically important drug interactions Routine serum concentration monitoring significant bronchodilation by 5 mcg/mL most will not have toxic symptoms when <15 mcg/mL Headache, nausea, vomiting, and insomnia when 15-20 mg/L Cardiac arrhythmias, seizures, and death when ≥20 mg/L
- 32. Algorithm for Theophylline Titration 32
- 33. Immunomodulators: Omalizumab (Xolair) 33 Mechanism: recombinant anti-IgE antibody prevents binding of IgE to mast cells & basophils decreases release of mediators following allergen exposure Indication (≥ 12 years old) moderate to severe persistent asthma Pts having a positive skin test or in vitro reactivity to aeroallergens allergic asthma not well controlled by corticosteroids Dosage/administration subcutaneous every 2 to 4 weeks dosage based on serum IgE level & weight Adverse effect anaphylaxis 70% occur within 2 hours may occur up to 24 hours after injection
- 34. Mast Cell Stabilizer 34 Mechanism Stabilize the cell membranes of inflammatory cells (mast cells, monocytes, macrophages), thus preventing release of harmful cellular contents no bronchodilatory effect Indications Adjuncts to the overall management of asthma Used solely for prophylaxis, NOT for acute asthma attacks(b/c Improvement in 1 to 2 weeks) Used to prevent Triggers or exercise-induced bronchospasm Alternative to initial ICS therapy but not as effective E.g. Cromolyn in MDI or nebulizer
- 35. Stepwise Approach for Chronic Asthma Management 35 National Asthma Education Prevention Program (NAEPP) recommendations categorized by age 0 to 4 years, 5 to 11 years, and ≥12 years Stepwise approach initial therapy based on asthma severity therapy adjusted based on asthma control Intermittent Asthma Only SABAs are need This classification of asthma includes patients with Exercise-induced bronchospasm (EIB), Seasonal asthma, or asthma symptoms associated with infrequent trigger exposure Patients pretreat with an SABA prior to exposure to a known trigger, such as exercise.
- 36. Persistent Chronic Asthma 36 Daily long term control therapy ICS are the long-term control medication of choice at all levels of severity and in all age groups SABAs are prescribed for all patients with chronic asthma for use on an as-needed basis. Monitor pts within 2 to 6 weeks to ensure that asthma control has been achieved Before increasing therapy, the patient’s inhaler technique and adherence to therapy is evaluated. If asthma controlled monitor pts at 1- to 6-month If asthma control has been maintained for at least 3 months…. Consider gradual stepdown in long-term controller therapy Current literature supports decreasing the ICS dose before removing the LABA, despite FDA warnings to use LABA
- 37. Stepwise Approach for Asthma Management
- 38. Stepwise Approach for Asthma Management
- 40. Treatment of Acute Asthma 40 Early and aggressive treatment is necessary for quick resolution Optimal treatment depends on the severity of the exacerbation Based on the initial response to SABA therapy, the severity of the exacerbation is assessed, and treatment is appropriately intensified Patients deteriorating quickly or not responding to quick-relief medications should go to the emergency department for assessment and treatment of the asthma exacerbation Pts responding to therapy in the ED with a sustained response to a SABA are discharged
- 41. Treatment of Acute Asthma 41 Pts who do not respond adequately to intensive therapy in the ED within 3 to 4 hours are admitted to the hospital. During hospitalization, oxygen, continuous nebulization of SABA, systemic corticosteroids, and alternative treatments such as magnesium may be used to treat the exacerbation Pts with oxygen saturation <90% (<95% in children, pregnant women, and patients with coexisting heart disease) receive oxygen with the dose adjusted to keep oxygen saturation above these levels Administration of low oxygen conc.(<30% of the fraction of inspired air) by nasal cannula or facemask is usually sufficient to reverse hypoxemia in most patients
- 42. 42Management of asthma exacerbations: home treatment
- 43. Hospital Care of Acute Asthma Exacerbations Continued on next slide 43
- 44. Continued from previous slide Hospital Care of Acute Asthma Exacerbations 44
- 45. Special Populations 45 Young children, especially 0-4 years many recommendations based on extrapolated data studies of ICS show improvement combination therapy inadequately studied Growth retardation may occur with ICS dose-dependent/transient/susceptible populations/ studies suggest reaching predicted adult height not affected Elderly osteoporosis risk increased with high dose ICS Pregnancy budesonide preferred ICS albuterol preferred for quick relief
- 46. Monitoring Therapy 46 Regular follow up 1 to 6 month intervals depending on control 3 month interval if step down anticipated Evaluate asthma control symptoms lung function validated questionnaires medication adverse effects adherence, environmental control, comorbid condition
Editor's Notes
- #7: Allergic/atopic/early onset asthma---rhinitis, urticaria, eczema, (+)skin tests, ↑IgE,(+) response to provocation tests with aeroallergens. Atopy is due to the genetically determined production of specific IgE antibody, with many patients showing a family history of allergic diseases Idiosyncratic/non-atopic/intrinsic asthma/late onset asthma--- no allergic diseases,(-)skin tests, normal IgE, symptoms when upper resp infection, sx lasting days or months and usually have more severe, persistent asthma.
- #30: The addition of ipratropium bromide to SABAs during a moderate to severe asthma exacerbation improves pulmonary function and decreases hospitalization rates in both adult and pediatric patients Combining an SABA with ipratropium is only indicated in the emergency department setting. There is no evidence to support continued use of ipratropium during hospitalization or for chronic asthma treatment
- #34: The most common adverse effects are injection site reactions and include bruising, redness, pain, stinging, may occur at any time after medication administration. Monitoring the patient for an anaphylactic reaction for 2 hours after medication administration is recommended for the first 3 months; thereafter, monitoring time can be reduced to 30 minutes It is also important to issue a prescription for and provide patient education on the use of subcutaneous epinephrine for an anaphylactic reaction from omalizumab.