Financial Disclosure. Pharmacy Technician Objectives: Definition: Pediatric Asthma Incidence, Pathogenesis, Severity and Treatment

Transcription

1 Pediatric Asthma Incidence, Pathogenesis, Severity and Treatment Roger Hefflinger, Pharm.D. Clinical Associate Professor Family Medicine Residency of Idaho Idaho State University College of Pharmacy Financial Disclosure I am not receiving any compensation from any of the manufactures of medications discussed during this presentation. College of Pharmacy Spring CE Programs 2015 Pharmacist, Nurse and Prescriber Objectives: Upon completion of the following discussion the health care provider in attendance shall be able to: Recognize common triggers associated with asthma in children and signs of severe exacerbation Recommend appropriate quick-relief and longterm control medications and appropriate delivery devices for infants and children with asthma Differentiate pharmacologic classes, routes of administration, and dosages of therapies available for pediatric patients with an acute asthma exacerbation Pharmacy Technician Objectives: Upon completion of the following discussion the pharmacy technician in attendance should be able to: List devices that assist medication delivery to pediatric patients with asthma Describe quick-relief medications and when they are used Describe long-term control medications and when they are used Governing Agencies for Asthma Recommendations and Guidelines Definition: Global Initiative for Asthma Management and Prevention GINA Newest: 2014 National Heart Lung and Blood Institute National Asthma Education and Prevention Program Expert Panel 3 Newest: 2007 Guidelines for the Diagnosis and Management of Asthma Asthma (AZ-ma) is a chronic (long-term) lung disease that inflames and narrows the airways. Asthma causes recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath, and coughing. The coughing often occurs at night or early in the morning. 1

2 Chronic-long term Inflammation - resulting in airway hypertrophy and narrowing Stopping/Slowing this process is hallmark of well controlled therapy Health Care Provider Applicable Points: causes recurring : wheezing chest tightness, shortness of breath, coughing Quick Relief medication are administered to reverse the acute processes Definitions: Asthma/COPD EP3- Comments Children ages 0 to 4 years: Diagnosis in infants and young children is challenging and is complicated by the difficulty in obtaining objective measurements of lung function in this age group. Caution is needed to avoid giving young children inappropriate prolonged asthma therapy. However, it is important to avoid underdiagnosing asthma, and thereby missing the opportunity to treat a child, by using such labels as wheezy bronchitis, recurrent pneumonia, or reactive airway disease. The chronic airway inflammatory response and structural changes that are characteristic of asthma can develop in the preschool years, and appropriate asthma treatment will reduce morbidity. Differential Diagnosing Pediatric Asthma: 2

3 Which of the following is a characteristic of Asthma? A. chronic irreversible disorder B. correlated with a smoking history C. has a poor response to corticosteroids D. chronic inflammatory disorder that predisposes the patient to periods of hyperresponsive airways Incidence/Prevelance Asthma affects more than 20 million people in USA Asthma affects more than 300 million worldwide Incidence differs around world (differences in identification and epidemiologic abilities) Asthma causes 250,000 deaths annually Deaths are decreasing (because of increase use of inhaled corticosteroids) Incidence is increasing worldwide Burden to Patient; Health Care Systems 2009 in USA: 2% of patients were admitted to hospital (>500,000 admissions) 8.4% were treated in the emergency room (>2,000,000 ER encounters) 53% reported an asthma attack in last year 42% reported asthma attack causing missed school or work day Children have higher rates of doctor visits than adults Death from asthma is 30% higher in females than males Death is 75% higher in African-American s than in whites Death is 7 x higher in patients 65 years or older than in children $1900-$3200 more health care costs than controls- = Billion Classifying Disease Severity and Control How many times having symptoms How many times having night-time symptoms Use of short acting beta agonists Interference with normal daily activities Number of exacerbations requiring systemic corticosteroids during each year Also a risk identifier 5-11 year olds can start to do pulmonary function testing and/or spirometric testing 3

4 Triggers: Viral infections have been implicated in most (>80%) asthma exacerbations in children Allergen sensitization, especially when there are more than three allergen triggers, is also associated with asthma exacerbation A growing body of evidence supports the view that viral infection and allergy interact to increase the risk of an exacerbation- Genetics! In the United States, more than 200,000 episodes of childhood asthma per year have been attributed to parental smoking Asthma Exacerbations are Seasonal Peaks in September: -Virus exposure -Allergen exposure - Combo of both Asthma Triggers Foods Nuts, Iodine, wheat, Exercise Inc in kids Allergens Pollens Pollution Perfume Virus Molds Humidity states Drugs NSAIDS You should understand WHY Sulfas Step One: Trigger Avoidance Eliminate animal dander Get rid of the animals Get rid of smoke exposure Wood burning stoves, campfires, second hand smoke Environmental identification Avoid, mold reduction, dust mite reduction Atopic individuals Anti-histamines, Nasal Steroids, Leukotriene antagonists Non-Sedating Antihistamines: Loratidine: Claritin, Alavert 10 mg OTC, Liq, Reditab Claritin-D 12 h, 24 h Desloratidine: Clarinex 5 mg RX Fexofenadine: Allegra 60 BID, 180 QD Allegra-D BID, Allegra-D 24 h Cetirizine: Zyrtec 5 mg, 10 mg, Liq Zyrtec-D BID Levocetirizine: Xyzal 5 mg QD How do we Determine EFFICACY? Dose-response curves of histamine in the human skin. Peripheral inhibition of histamine-induced weal by loratadine ( L; 10, 20, 40 mg) and cetirizine ( C; 2.5, 5, 10 mg) 8 hours after drug.(from De Vos C: Clin Exper Allergy 19: , 1989.) 4

5 Which of the following non-sedating antihistamines is the least potent? Standard Step Care 0-4 years A. Cetirizine Zyrtec10 mg B. Fexofenadine Allegra 180 mg C. Hydroxyzine Atarax 25 mg D. LoratidineClaritin 10 mg Standard Step Care 5-11 years Quick Relief Medications Short Acting Beta Agonist (SABA) Pharmacology Must Know Physiologic Cascade Number 1 -rgh Beta-2 = Bronchial smooth muscle relaxation Of course it can t be that simple! Short Acting Beta Agonists: Albuterol: MDI: Proair HFA Ventolin HFA Proventil HFA Solution for Nebulizer: 2.5 mg/3 ml 1.25mg/3 ml, gen Accuneb 0.625mg/3 ml, gen Accuneb Levalbuterol MDI: Xopenex Solution for Nebulizer: Xopenex 5

6 How To Use an HFA MDI? Most common SABA Question Remove dust cap Shake well suspensions Exhale SLOWLY Place in mouth tight lips Or 3 fingers breadths? Begin SLOW DEEP inhalation Press canister Continue inhalation to maximum Hold breath 10 seconds (comfort) Exhale SLOWLY Wait 30 seconds repeat 1-10 minutes? What about the HR differences? Theory Racemic SR Albuterol equal parts R albuterol (Levalbuterol) 100 x more potent on beta receptors S albuterol cause more beta-1 tachycardia? Levalbuterol Heart Rate Studies Overall, 75% (106/142) in the racemic albuterol group received 2.5 mg (1.25 mg R-albuterol) and 55% (22/40) in the levalbuterol group received 0.63 mg Quick Relief Medications: Short Acting MuscarinicAntagonists (SAMA) Pharmacology Ipratropium Short Acting- 4-6 hours Atrovent HFA Soln for Nebulization Combinations Combivent (Plus Albuterol) Duoneb Solnfor Neb Long Term Control Medications: Corticosteroids Preferred agents to decrease the airway remodeling and hypertrophy secondary to long standing over active inflammatory cascade. 6

7 Inhaled Corticosteroids Inhaled Equipotent Doses MDI: HFA Flunisolide Aerospan 80 mcg puff DPI: Beclomethasone Powder for inhalation QVAR reg 40 mcg 1-2 puffs BID, 80 mcg 1-2 BID Fluticasone 44, 110, 220 mcg Flovent HFA,2-4 puffs BID Flovent Discus 50 mcg 1-4 BID Budesonide Pulmicort Flexihaler 90 or 180 mcg puff Soln for nebulization Mometasone Twisthaler Asmanex 220 mcg Ciclesonide Alvesco 80, 160 mcg Which immediately brings up an important point-can a 0-4 year old or a 5-11 year old use a HFA or DPI properly? Nebulizers: GINA VHC= Valve Holding Chamber Portable Nebulizers Counseling points: SE Corticosteriods Corticosteroids cause thrush Rinse the mouth Medium to High dose cause insulin resistance May worsen diabetes Adjust accordingly Corticosteroid Agitation in pediatric patients Clean/change out the tubing Associated cost 7

8 What about growth suppression Price Out: PulmicortRespule 0.5/2ml 30 vials AWP-$369.26, Generic $332.42/30 vials ($90.00 ACQ) PulmicortRespule 0.25/2ml 30 vials AWP-$313.75, Generic $282.42/30 vials ($89.00 ACQ) Plus nebulizer rental Plus new tubing etc = Expensive but sometimes the only way Long Term Control Medications: Leukotriene Receptor Antagonists Must know physiologic cascade number? - Leukotriene D4 Receptor Antagonists: - Montelukast Singulair : - Generic available 10 mg QD adults 5 mg QD children mg chew tab 2-5 y/o - Zifurlukast: Accolate 20MG BID, 7-11y/o-10 mg BID Generic Available Food Decreases Bio-availability = Empty stomach Inx with Coumadin increase coumadin response Long Acting Beta Agonists Only used as second line long term control Salmeterol Serevent Diskus 50 mcg/puff Powder for inhalation 12- hour DOA Never for quick action Onset minutes Formoterol Foradil Dry powder for inh (DPI) 12 mcg/puff Soln for nebulization Perforomist 20 mcg Never by themselves in asthmatics Arformoterol Brovana 15 mcg/2ml Soln for nebulization Indacaterol Arcapta Neohaler 75mcg Inhal Q day COPD Only at this time Olodaterol Striverdi Combination Steroids/LABA Fluticasone + Salmeterol = Advair Diskus: 100/50(green), 250/50(yellow), 500/50(red) Advair HFA: 45/21 (green), 115/21(yellow), 230/21(red) BID Budesonide + Formoterol = Symbicort 80/4.5 (Green), 160/4.5 (Blue) Mometasone + Formoterol = Dulera 100/5 (Yellow), 200/5 (Purple) Fluticasone + Vilanterol = Breo Ellipta 100/25 8

9 Long Term Control Medications: Methylxanthines MOA CLASSIC: Weak bronchodilator Promotes respiratory drive Decrease diaphragm fatigue Phosphodiesterase inhibitor NEWER MOAS Blocks adenosine receptors Mild anti-inflammatory effects Blocks phosphodiesterase type 4 enzyme MAST CELLS, MACROPHAGES, EOSINOPHILS Histone Deacetylase interactions Makes corticosteroids more effective Immune Modulators Omalizumab, a recombinant DNA-derived humanized monoclonal antibody to the Fc portion of the IgE antibody, binds to that portion preventing the binding of IgE to its high-affinity receptor (FcεRI) on mast cells and basophils. The decreased binding of IgE on the surface of mast cells leads to a decrease in the release of mediators in response to allergen exposure Not FDA approved in infants and children Acute Exacerbation Management Equipotent Systemic CS: Albuterol SABA Plus Ipatropium SAMA Duonebs - Q hour, Continuous Nebulization Systemic Corticosteroids 1 mg/kg Prednisone or Equivalent per day EP3 may go up to 2mg/kg in infants and children not to exceed 60 mg Pulse vs Taper Modified from Goodman and Gilman s Severe Exacerbation Magnesium Sulfate mg/kg IV (1-4 grams IV) Improves FEV1 Shortens Hospitalizations Nebulized Magnesium Sulfate: Being studied +/-results at this point Helium Oxygen Heliox is a blend of helium and oxygen in concentrations ranging from 60% to 80% helium and from 20% to 40% oxygen The role of heliox in acute asthma remains con-troversial and it is generally limited to centers experienced in its administration. Which of the following would be considered a low dose inhaled corticosteroid in a child? A. Budesonide 400 mcg B. Beclomethasone 100 mcg C. Fluticasone 500 mcg D. Mometasone400 mcg 9

10 Prevention/Education Opportunities Home Peak Flow Monitoring Asthma Action Plans Asthma Control Test ACT Lower the Number Worse the control Current debate about where is the cutoff for good control or poor control: <19? Deschildreet al. Asthma control assessment in children Study to evaluate the: GINA 2006 strict GINA strict without taking into account exacerbations NAEPP CRITERIA Physicians Assessment Compared to parental C-ACT 525 Children C-ACT Results: Deschildre The optimal C-ACT cutoff point that correctly predicted not controlled children was 22 (GINA strict) or 21 (GINA symptoms, NAEPP, physician s assessment). Severe Exacerbations Infants A C-ACT score < 14 (GINA symptoms) or < 17 (physician assessment) Improved the accuracy to detect that asthma was not controlled 10

11 Severe Asthma Tiotropium, Aclidinium, Umclidinium (LAMA) The addition of tiotropium to the regime of patients symptomatic despite ICS therapy was superior to doubling the dose of ICS and equivalent to adding LABA. There is no pediatric study on tiotropium therapy in asthma, but there is an urgent need to explore its role Macrolide Antibiotics Anti-Fungal Therapy Azoles (Fluconazole) to reduce fungal load and IGE Cytokine Antagonists IL-13, IL-5 monoclonal antibodies Hedlin Future Research Questions: What is the safety profile of biologic agents for the treatment of asthma that are used over long time periods? What is the long term efficacy of biologic agents for the treatment of asthma? Can these novel drugs prevent airway remodeling? What is the safety and efficacy profile of biologic asthma drugs in children? How will clinicians choose between different biologic therapies as they become available and can we identify novel biomarkers that can predict responsiveness? What are the potential therapeutic targets in patients with non-eosinophilic and corticosteroid resistant asthma? Which of the following is the leading cause of asthma exacerbations in children? ASSESSMENT QUESTIONS FOR PHARMACISTS, NURSES AND PRESCRIBERS A. Medication nonadherence B. Over reliance on SABA medications C. Use of low dose inhaled corticosteroids D. Viral upper airway infections Which of the following is a marker of increased risk and poorly controlled moderate persistent asthma? A. Medication nonadherence B. Over reliance on SABA medications C. Use of low dose inhaled corticosteroids D. Viral upper airway infections Which of the following is the preferred first line therapy in asthma patients to prevent the disease progression? A. Medication nonadherence B. Over reliance on SABA medications C. Use of low dose inhaled corticosteroids D. Viral upper airway infections 11

12 Which of the following medications can be considered to be Quick Relief Medications for pediatric patients with asthma? ASSESSMENT QUESTIONS FOR TECHNICIANS A. Budesonide B. Fluticasone C. Montelukast D. Albuterol Which of the following can be considered a preferred Long Term Control medication for pediatric patients with asthma? A. Budesonide B. Fluticasone C. Montelukast D. Albuterol Which of the following medications can be considered an alternative to medium dose inhaled corticosteroids or LABA for pediatric patients with Asthma? A. Budesonide B. Fluticasone C. Montelukast D. Albuterol References: GINA. MasoliM, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy2004;59: Vital signs: asthma prevalence, disease characteristics, and self management education: United States, MMWR MorbMortal Wkly Rep 2001:60: HedlinG. Management of severe asthma in childhood-state of the art and novel perspectives. PediatAllergy Immunol2014;25: Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ 2014;349: g5517 AnselmoM. Pediatric Asthma Controller Therapy. PediatrDrugs;2011:13(1):11-17 Daley D. The evolution of the hygeinehypothesis: the role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseases. CurrOpin Allergy Clini Immunol 2014;14; RanceKS, Trent CA. Profile of a Primary Care Practice Asthma Program: Improve Patient Outcomes in a High-Risk Population J Pediatr Health Care. 2005;19:25-32 DeschildeA, et al. Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C-ACT) and physician s rating. Allergy 2014;69: