Respiratory Medications and Devices Update 2/15 Dewey Hahlbohm, PA-C, AE-C Wendy Brown, Pharm.D., MPAS, PA-C, AE-C Objectives! Review mechanism of action for asthma pharmacologic agents! Describe key patient educational points for each! Compare and contrast various aerosol delivery devices including proper technique and limitations of device! Outline care and cleaning of devices
Pharmacotherapy! Antiinflammatory (controller/maintenance) versus bronchodilators (rescue/reliever) meds! Educate pts,! Role of medications! Role of monitoring! Role of treatment plans Long-term control medications! EPR-3 recommends long-term control medications be taken on a daily basis for treatment of persistent asthma! Inhaled corticosteroids (ICS)! Inhaled long-acting bronchodilators (LABA)! Leukotriene modifiers (Singulair)! Theophylline! Immunomodulators
Inhaled corticosteroids (ICS)! Most potent and consistently effective long-term control medication for treatment of asthma! Work on Airway inflammation through a variety of mechanisms! Effects: Decrease severity of symptoms, improve control and QOL, improve peak flow and spirometry, prevent exacerbations and decrease systemic corticosteroid use, ED visits, hospitalization and death Benefits of ICS! Increase number of!2- adrenergic receptors and improve the receptor responsiveness to!2- adrenergic stimulation?! Reduce mucous production and hypersecretion! Reduce bronchial hyperresponsiveness! Reduce airway edema and exudation
ICS: Local Adverse Effects! Oral candidiasis (thrush)! 45-58% of patients have + cultures (clinical thrush 0-34%)! Not as common with lower doses (5%)! Dysphonia! 5-50% of patients! Reflex cough and bronchospasm ICS: Systemic Adverse Effects! Linear growth:! Low-med dose ICS may have potential to decrease growth velocity in children! Effects are small and may be reversible! Studies show improved asthma outcomes in children! Expert Panel statements:! Risk is well balanced by benefits! Effects may be dose dependent! Poorly controlled asthma may delay growth in children! Effect typically occurs in first several months! Growth should be monitored
Generic Brand Dose/actuation notes Fluticasone Flovent 44, 110, 220 mcg 100, 250, 500 mcg HFA MDI Discus Triamcinolone acetonide Azmacort 100 mcg MDI with built in spacer Beclomethasone dipropionate QVAR 40 mcg 80 mcg HFA MDI Flunisolide Aerobid 250 mcg HFA MDI Budesonide Nebulizer suspension Pulmicort 200 mcg 0.25, 05 mg DPI, Turbuhaler Only available product for neb Mometasone furoate Azmanex twisthaler 110 mcg 220 mcg Breath-activated Once daily dosing Ciclesonide Alvesco 80 mcg, 160mcg, MDI, once daily dosing Dosing of ICS Ciclesonide Inhaled 80, 160 mcg/puff NA NA 320mcg NA NA >320-640mcg NA NA >640mcg Adapted from: http://www.health.ny.gov/diseases/asthma/pdf/ 2009_asthma_guidelines.pdf
Combo Products Product Dosage Form Dose Fluticasone/ Salmeterol (Advair ) DPI: 100/50; 250/50; 500/50 HFA: 45/21; 115/21; 230/21 1 blister q 12 hours 2 inhalations q 12 hours Discus approved for kids >4 HFA approved for kids > 12 Budesonide/ Formoterol (Symbicort ) HFA: 80/4.5; 160/4.5 Two inhalations twice daily Approved for kids >12 Mometasone/ Formoterol (Dulera ) HFA: 100/5; 200/5 Two inhalations twice daily Approved for kids >12
Inhaled Corticosteroids Teach patient: About delay of onset Importance of taking every day Proper technique Use spacer for MDI RINSE and SPIT after each use Decrease oral thrush, dysphonia When to change canister Fear of steroids is common/need to provide accurate counseling/education to pts Leukotriene Modifiers Work on arachadonic acid cascade! Block leukotriene D4 (potent vasoconstrictor)! D4 at least 1000 times more potent than histamine! Leukotrients are inflammatory mediators that mediate airway obstruction, hyperresponsiveness and inflammation
Leukotriene Modifiers Dosage Form Adult dose Child Dose Comment Montelukast Singulair 4,5 mg chewtabs 10 mg tab 10 mg qhs Age: 2-5 y.o 4 mg qhs Age: 6-14 y.o. 5 mg qhs Age: >14 y.o. 10 mg qhs Has captured nearly all of the market for leukotriene modifiers Zafirlukast Accolate Zileuton Zyflo 10, 20 mg tab 20 mg bid Age: 7-11 10 mg bid 300, 600 mg tab 2400 mg qday 300-600 qid Has not been studied in kids <12 y.o Take 1 hr before/2hr after meals Monitor LFTs Monitor LFTs Long-Acting Bronchodialators (Beta 2 agonists)! EPR-3: Preferred adjunctive treatment to ICS for longterm control for step 3 in adults and children >12; steps 4 and 5 for kids 5-11 y.o. for long-term control of symptoms! Not recommended as monotherapy! No anti-inflammatory properties! Not recommended to treat acute symptoms
Long-Acting Bronchodilators (Beta 2 agonists)! MOA: relax bronchial smooth muscle by stimulating B2 receptors! B2 receptors found throughout respiratory tract! Duration of action: 12 hours not to be used more than twice daily LABA Indications: adjunctive therapy for moderate-severe persistent asthma Should NOT be used for EIB Products: Formoterol (Foradil ) 5 minute onset Salmeterol (Serevent ) 30 minute onset ADRs: headache, palpitations, tremor, nausea and vomiting
Long-Acting Beta-2 agonists: Therapeutic Issues: SMART Trial (Serevent Multi-center Asthma Research Trial) www.fda.gov/medwatch/safety/ 2003.servent.htm! Compared to placebo: Serevent MAY be associated with increased risk of respiratory-related deaths/resp.- related life-threatening experiences! More prominent in African-Americans! Steroids under-utilized in SMART trial! LABAs should never be used as monotherapy
Combo products Product Dosage Form Dose Fluticasone/ Salmeterol (Advair ) DPI: 100/50; 250/50; 500/50 HFA: 45/21; 115/21; 230/21 1 blister q 12 hours 2 inhalations q 12 hours Discus approved for kids >4 HFA approved for kids > 12 Budesonide/ Formoterol (Symbicort ) HFA: 80/4.5; 160/4.5 Two inhalations twice daily Approved for kids >12 Mometasone/ Formoterol (Dulera ) HFA: 100/5; 200/5 Two inhalations twice daily Approved for kids >12
Combination Therapy
Omalizumab (Xolair )! EPR-3: recommended for step 5 and 6 care in patients who have allergies and who are inadequately controlled by high-dose ICS and LABA! Recombinant Anti-IgE monoclonal antibody! MOA: binds free IgE and IgE mast cells which leads to decrease in the release of mediators in response to allergen exposure! Approved in ages >12 y.o. with allergic asthma! Subcutaneous injection q 2-4 wks depending on baseline IgE levels and pts wt! Anaphylaxis has occurred: administered under medical supervision Anticholinergics! Limited role in asthma/first line in COPD! MOA: Inhibits muscarinic cholinergic receptors! Bronchodilation, reduces intrinsic vagal tone, may reduce mucous gland secretions! Adverse Effects: Dry mouth! Do not block EIB
Anticholinergics Long Acting Muscurinic Antagonists (LAMAS)! Tiotropium (Spiriva )! Convenient qday dosing via handihaler! Respimat formulation just released in 2015! Peak effect in 3 hours, durations 24 hours! Aclidinium (Tudorza)! Breath-actuated DPI: BID dosing! Duration 12 hours Tiotropium (Spiriva )! Long acting inhaled anticholinergic indicated for COPD. No role in asthma treatment
(Aclidinium bromide)tudorza! Long acting anticholinergic: Not indicated for asthma Anticholinergic Short acting Muscurinic Antagonists (SAMA)! Ipratropium bromide (Atrovent ):! Used with short-acting B2 agonist in multiple doses in moderate to severe asthma exacerbations in the emergency department! Combination product (albuterol/ipratropium-atrovent ) off of the market! Combivent respimat new product to replace atrovent! Peak affect 1.5-2 hours, duration 4-6 hours
Combivent Respimat Quick-relief medicine! Prompt reversal of bronchoconstiction and accompanying symptoms (cough, chest tightness, wheeze, etc)! Short-acting B2-agonists! Anticholinergics! Systemic corticosteroids! Used for exacerbations
Short-acting B2-agonists! Smooth muscle relaxation! Rapid-onset of action: 10-15 min! Duration of action: 4-6 hours! Use q 4 hours PRN (routine dosing discouraged)! May use 15-30 min before exercise to prevent symptoms! Should always be available to patient Beta-2 Agonists Potential Adverse effects of both LABA and SABA Frequency and severity of ADRs directly related to dose and dosing frequency For typical short-acting, inhaled beta-2 agonists Frequency 1-5% Typical ADR s Headache/dizziness/vertigo Palpitations Tremor Nausea/vomiting ADRs with overuse: Hypokalemia Prolonged QTC interval
Short-acting B2-Agonists: Warning Signals! Needing more than every 4 hours! Needing every 4 hours all day long! Not responding to treatment within 15 min! Control: needing quick-relief less than twice weekly Short Acting B2 Agonist Albuterol HFA MDI (Pro-Air, Proventil, Ventolin) Also available as solution for nebulizer Levalbuterol MDI (Xopenex) Also available as solution for nebulizer
Inhaled Medication! Advantages! Rapid Onset of Action! Low incidence of systemic side effects! Success of inhaled medication dependent on:! Medication deposition! Particle size (2-5 microns desirable)! Inhalation mode! Patient features
Optimum inspiratory flow! Delivery to lungs is dependent on inspiratory airflow and medication device resistance! Inspiratory flow requirements may vary between devices Optimum inspiratory flow! Device Optimum Inspiratory Flow! Diskus 30-90 L/min! Flexhaler 60-90 L/min! Autohaler 30-60 L/min! MDI 25-60 L/min! Aerolizer 25-90 L/min! Twisthaler 30-60 L/min! Handihaler 20-90 L/min
Metered Dose Inhaler! Teach closed mouth technique! 10-30% of the dose from the MDI delivered to lungs, 80% is swallowed! Problems:! Techniques! Hand lung coordination! Too brief breath hold! Inspiratrory flow too rapid! Insufficient canister shaking! Spraying in mouth breathing through the nose Metered Dose Inhaler! Technique:! Shake 6-10 times! Tilt head back slightly and breathe out slowly to empty lungs! Position the inhaler in mouth, between teeth with lips around the mouthpiece! Press down and slowly breath in for 3-5 seconds! Hold breath 10 seconds! Wait 1 minute before another puff
Factors affecting Dose Uniformity With Metered Dose Inhalers! Factors affecting Dose uniformity with MDI! Loss of Prime! Problem: After period of no use, first dose may be reduced or absent! Cause: Propellant drained from metering chamber! Loss of Dose! Problem: Dose diminishes, but is unnoticed because propellent remains the same! Cause: Active ingredient creams or settles! Tailing off! Problem: Erratic drug delivery after labeled number of doses! Cause: Metering chamber fills with vapor rather than propellent Education for dose uniformity! When to prime! Clean device! Remove canister: rinse in warm water! Clean at least once/week and as often as daily White stuff around the mouth piece can slow delivery! Teach patient to know when inhaler is gone: either tick method(count number of puffs used(easier to do with maintenance meds), or check dose counter
Spacers! Enhance aerosol delivery! Decrease need for coordination! Decrease systemic side effects! Reduce deposition in the oral cavity! Required for corticosteroids (decrease incidence of local side effects) Dry Powder inhalers for asthma! Diskus (Serevent, Flovent, Advair) multidose discrete dose! Flexhaler (Pulmicort) -- multidose reservoir! Twisthaler (Asmanex) multidose reservoir! Aerolizer (Foradil) single dose discrete dose
Dry Powder Inhalers! Fast deep breath as opposed to slow deep breath with MDI! General Care:! Keep dry at room temp! Never put in water! Wipe mouthpiece with tissue to clean! Never shake after dose is loaded! Never breath in to device Dry Powder Inhaler! Advantages:! No propellants! Improved Airway deposition! Eliminated need for spacer! Easy to teach and learn! Dose counters are included! Disadvantages:! Ability to be affected by humid air! No quick relief devices! Different devices require different flowrates technique isn t standardized
Diskus (Advair, Flovent)! Diskus DPI:! Mulitdose (60 doses)! Delivers about 90% of labeled dose at wide range of flow rates! Desirable for pts who have fluctuating flow rates with variation of ds.! Counter! Advantage: if you forget to put lever back you meet resistance! Use: click, click, breath in strong, steady and as deeply as possible, close to reset
Pulmicort Flexhaler! Multidose: 180 mcg 120 doses; 90 mcg 60 doses! More resistance to inhalation and requires more forceful inspiratory flow rates for consistent dosing! Variability of doses at different flow rates is higher than other devices! Dose indicator below mouthpiece red 20 doses! Priming: done with a new device! Remove Cover! Twist brown grip on bottom fully to the right then back to the left! You will hear a click, Repeat Pulmicort flexhaler! Using:! Remove cover! Hold upright! Twist brown grip fully to left then right click! Place in mouth! Breath in as quickly and deeply as possible! Hold 10 seconds! Replace cover twist to close
Asmanex Twisthaler! Multi-dose DPI. Contains 30,60, or 120 doses.! Use:! Open: hold the inhaler upright with the base on the bottom! Grip the base and twist the cap counterclockwise while keeping the inhaler in an upright position! As the cap is lifted off the dose counter counts down by one! Inhale dose: exhale fully, firmly close lips around the mouthpiece and take a fast, deep breath while holding the mouthpiece in a horizontal position,! Remove the inhaler from your mouth and hold breath for 10 seconds! Replace the cap and twist it clockwise until it clicks(the cap must be fully closed to load the next dose! Check to make sure that the arrow is lined up with the dose counter Asmanex Twisthaler
Foradil Aerolizer! Use! Dose placed into device before using! Capsule in foil! Pierce capsule! Never breath into mouthpiece! Whirring noise when inhaling should be heard! Sweet taste! Always discard empty capsule! Breath in rapidly steadily and completely Nebulizers! Advantages! Coordination of inspiration and treatment not required! use in infants, children, elderly, patient preference: allows slower, relaxed breathing during asthma flare, use for acute exacerbations! Disadvantages:! Cost and care issues! Length of treatment! Portability
Nebulizers! In general we should encourage patients to use MDI/DPI: can get same amount of medication with proper technique and much more convenient! Blow by technique used when mask intolerable. Directs aerosol towards nose and mouth with reservoir tube. NO DATA behind this.! Better to administer with close fit mask when child is asleep Nebulizers! Crying: completely prevents lower airway deposition in distressed child! "Kids <5 should use close fitting mask for nebs! Pulmicort respules should always be given with sealed mask to prevent getting in eyes, wipe mouth after use! Mouthpiece can start to be used around the age of 5! Pulmicort is the only ICS for nebulizer! "Dead volume: give neb until it sputters then tap and when it sputters no more will come out. The amount left is referred to as the dead volume This may be up to 1 ml depending on the neb
Nebulizers! Disposable Nebulizer! Changed every 2 weeks with regular daily use! Wash daily with mild detergent! Rinse well in running water and air dry completely! Disinfect regularly 1:3 dilution of white vinegar and water! Every 3 rd day! Soak 20 min rinse well air dry! Reusable Nebulizer:! Cleaned and reused for up to 6 months! Some dishwasher safe! Store in plastic ziplock bag once dry! Neb cup rinsed after each treatment to eliminate leftover meds Only in Montana
Questions? Thanks for being here, enjoy the rest of your Asthma Educator Conference