Respiratory Medications and Devices

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 hyper-responsiveness

!  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

!  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

N Engl J Med. 2012;367:904-912

Generic Brand Dose/actuation notes

Fluticasone Propionate

Flovent 44, 110, 220 mcg 100, 250, 500 mcg

HFA MDI Discus

Fluticasone Furoate

Arnuity 100, 200mcg DPI, Ellipta

Beclomethasone dipropionate

QVAR 40 mcg 80 mcg

HFA MDI

Flunisolide Aerospan 80mcg HFA MDI with built in spacer

Budesonide Nebulizer suspension

Pulmicort 90, 180 mcg 0.25, 0.5, 1 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

Asthma Care Quick Reference. https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_qrg.pdf

Product Dosage Form Dose

Fluticasone Propionate/ Salmeterol (Advair®)

DPI: 100/50; 250/50; 500/50 HFA: 45/21; 115/21; 230/21

1 blister q12 hrs 2 inhalations q12 hrs

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

Fluticasone Furoate/ Vilanterol (Breo®)

DPI: 100/25mcg; 200/25mcg One inhalation once a day

Approved for patients 18 years and older

Combo Products

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

Long-Acting Bronchodilators (Beta 2 agonists)

!  EPR-3: Preferred adjunctive treatment to ICS for long-term 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

Long-Acting Beta-2 agonists:

Should not be initiated in patients with significantly worsening or acutely deteriorating asthma, which may be a life-threatening condition.

Should only be used long-term in patients with asthma not adequately controlled with inhaled steroids or other controller medications. Should be used for the shortest time possible to achieve symptom control. Once patients are no longer experiencing symptoms, LABAs should be discontinued if possible with patients maintained on single controller medications alone. Children and adolescents needing a LABA should use a combination product that also contains an inhaled steroid to ensure compliance with both medications.

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

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 3rd 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

!  Dewey Hahlbohm hahlbohmd@earthlink.net

!  Wendy Brown wendy.brown@ndsu.edu