1. You Can Breath Easy, We Have You Covered (An Inhaler Therapy Review)
Idaho Society of Health-Systems Pharmacists
You Can Breath Easy, We Have You Covered (An Inhaler Therapy Review)
Mikaela Elwell, PharmD
Andrea Brauer, PharmD
PGY1 Pharmacy Resident
St. Luke’s Health System – Boise, ID
03/04/2016

2. Disclosures The presenter has no disclosures to report
No medications will be discussed off-label in this presentation

3. Learning Objectives
Describe inhalers by their modes of aerosol delivery: metered dose inhalers, dry powder inhalers, propellant free liquid inhalers, or nebulizers.
List the desired properties of inhalers as well as patient specific factors that impact medication delivery to the airways and the purpose of a spacer as an accessory device.
Identify the common disease states in which inhaler therapy is utilized for respiratory conditions.

4. http://museum.aarc.org/gallery/aerosol-delivery-devices-2/(mid 1800’s)
1500 BC
400 BC
1778
Mid-1800s
1930’s
1950’s
TODAY
To start, I thought we would begin with a brief history of the evolution of the ways we have been inhaling medications
In1500 BC in Egypt, a hot brick was used to vaporize liquid thrown on it so that could be then inhaled.
400 BC Hippocrates is attributed with designing a simple pot with a reed in the lid so vapors could be inhaled
Pot and reed variations were used until John Mudge in 1778 developed the first “inhaler” device for inhaling opium vapor to treat cough.
The first atomizers or what we know today as nebulizers were developed in the mid-1800s
Hand bulb nebulizers were developed in the 1930’s that utilized electricity or compressed air
Finally, the first pressurized MDI (pMDI), and what we still use today, was developed in 1955, when an asthmatic teenager got an idea from her perfume spray device and suggested it to her father, the president of Riker Labs (now known as 3M Pharmaceuticals).
Now with technological advances we have a variety of ways to inhale medications.
Anderson PJ. Respir Care. 2005;50(9):
1800’s)
Anderson PJ. Respir Care. 2005;50(9):
The Pharmaceutical Journal, Vol. 277, p795(1950s)

5. Inhaler Therapy Targeted drug delivery Rapid onset of action
Advantages
Disadvantages
Targeted drug delivery
Fewer side effects
Smaller doses required
Rapid onset of action
Less invasive portal
Dose estimation
How much really gets into the lungs?
Consistency hard to achieve
Patient’s use is variable
Age / physical ability
Technique dependent
So why do we use inhaler therapy?
Many advantages, the first of which is targeted drug delivery. When we can get the medication to go to the site where we want it to work and not many other places, we get fewer side effects and we need less drug for effect, it is not wasted by the digestive tract
Not passing through the GI tract saves time and so you get a faster onset of action
Additionally, it can still provide a means for getting medicine to the general circulation but in a less invasive way of administration than with IV medications though we are going to focus on inhalers for respiratory conditions.
Aerosols in the Health Care Field. Accessed Online at: 1/9/2016

6. Inhaler Considerations
When looked at another way, there are many factors that play into achieving optimal delivery of medication into the lungs. As we mentioned patient specific factors such as age, whether or not they have the knowledge of how to use their inhaler, and whether their lung tissue.
If you think back to the timeline of inhaler therapy, technology drives what is possible and our ability to pair a medication with its innate physical properties of stability, solubility, etc. and the ability to develop a device that works with the physical properties of the medication and get it into a small enough particle size to actually get down into the lungs, have it be user friendly, consistently deliver the same dose of the medication, and not cost an arm and a leg.
So there are many factors that drive inhaler design and unlike swallowing a pill, or having to prick yourself with a needle, inhalers require a person to have advance knowledge of how to operate. By understanding the type of inhaler you may be using, from pMDI, DPI or nebulizer, it will help you know HOW to use it.
Fig.2 Taken from: Ibrahim M. et al. Med Devices: Evidence and Research. 2015;8:131-9
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7. A spacer should only be used with what type of inhaler to help enhance a patient’s use?
Metered dose inhalers
Dry powdered inhalers
Nebulizers
A & B
All of the above
Correct Answer: A. Metered dose inhalers

8. Pressurized Metered Dose Inhaler (pMDI)
Propellant = Hydroflorocarbon (HFA) Drug in suspension = Must Shake
Technique:
Shake 5 sec (suspension)
Take off cap, hold upright
Breath out (all the way)
While pressing inhaler – Breathe in SLOW & DEEP (Propellant is doing the work)
Hold breath as long a possible (10 sec)
The pMDI is the “classic inhaler” we all think of when we picture an albuterol inhaler.
As the name implies, there is a metering valve that allows the same amount of drug out each time the canister is pressed and it is the chemical propellant in the pMDIs that allows this type of device to work.
For decades, what was the chemical propellant used in MDIs and all aerosol cans? – CFC (Chlorofluorocarbons) and as you may remember it was discovered that CFC depletes the ozone layer (important for filtering out the harmful rays of the sun) and was banned internationally. So the MDIs needed to be redeveloped with a new propellent. We only have brand name albuterol inhalers on the market today because the redevelopment removed all generic albuterols and replaced them with the currently branded inhaler that now uses hydroflorocarbon (HFA) as the propellant.
So if there is HFA in the name of the inhaler, you know that it is a MDI
The drug is in a suspension (exception QVAR and Alvesco) with the propellant and therefore you must shake the inhaler to ensure even mixing and consistent dose is released everytime
Knowing the mechanism behind the pMDI now makes sense for the proper technique to use.
Holding the breath for as long as possible allows time for the medication to deposit in the lungs before you exhale it out.
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9. Spacer Use with pMDI pMDI Coordination is difficult
Advantages
pMDI Coordination is difficult
Children & elderly
Create aerosol faster than a person can inhale
Medication deposits in mouth and does not reach lungs
No need to time breath
Reduces speed of aerosol
Prevent thrush
From inhaled corticosteroids
Indicate correct inhalation speed
Whistles if too quick
Image:

10. Dry Powdered Inhalers (DPIs)
Rotate / Twist
Drug in loose powder form
Micronized drug particles
1-5µm
Pierce tablet
Slide / Click
Require maximal inhalation force which is hard to do
Image:

11. Dry Powdered Inhalers (DPI)
Advantages
Contain NO propellant
Breath Activated
Fewer coordination issues
No spacer needed
No need to hold breath
Technique
Open/Load device
Breath out (all the way)
Quick & Forceful Inhale
Breath must do the work
Disadvantages
While there are many types of DPIs, they all have the same formulation design – dry/loose powder that is micronized
They contain no propellant and typically rely on the patients breath to activate which avoids the coordination issue we have with pMDIs
What is one of the steps in technique that is necessary with pMDI but should be avoided with DPIs?
Shaking or even tipping when the medication is exposed – after a twist, slide, click, or peirce of the tablet you do not want to loose the medication
Must have adequate inhalation
Age dependent
Progression of disease state

12. Nebulizers Sound waves atomize liquid Compressed air atomizes liquid
Ultrasonic
Sound waves atomize liquid
Jet
Compressed air atomizes liquid
Without going into too much detail, there are three types of neublizers. They all take liquid medication and aerosolize it. Jet nebs utilize high speed air to create vapor as liquid passes across a baffle, ultrasonic uses sound waves. Newest to the market are the vibrating mesh and they use laser drilled mesh to vibrate liquid and as it passes through the mesh it becomes atomized.
Vibrating Mesh
Laser drilled mesh vibrates to atomize liquid
Ibrahim M. et al. Med Devices: Evidence and Research. 2015;8:131-9
Images:

13. Nebulizers No coordination required Allows large doses of medicine
Advantages
Disadvantages
No coordination required
Allows large doses of medicine
Option for those who cannot use pMDI or DPI
Pediatric
Elderly
Unconscious
Too ill
Soft mist
Less portable / convenient
Longer time to set-up / use
Expensive
Like dry powder inhalers, nebulizers do not require coordination of breath and activation of device and therefore they are useful for pediatrics, elderly, unconscious patients, or for those that are too ill to use pMDI or DPIs
They can also deliver larger doses than pMDI or DPI which may be needed in some situations
Of course you do not often see nebulizers except in the hospitals because they can be rather expensive, harder to take with you if you are running around, and are certainly not as convenient.
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14. Soft Mist Liquid Inhaler (Respimat®)
Advantages
Disadvantages
Small / Portable
No power supply needed
No chemical propellant
Soft mist – less deposition in throat
Not breath activated
Expensive
Combines the advantages of pMDIs and nebulizers
Rather than needing compressed air or a power source like other medications, it utilizes a spring, that when twisted creates the force needed to push the medication through a fine filter
Soft mist unlike pMDIs means less drug is deposited in the throat and more makes it down into the lungs
Right Image:
Left Image:

15. Respiratory Conditions

16. Inhaler therapy is used in patients with the following conditions?
Cystic Fibrosis
Chronic Obstructive Pulmonary Disease
Asthma
Diabetes
All of the above
Correct Answer: E. All of the above

17. Respiratory Conditions
Asthma
Chronic Obstructive Pulmonary Disease
Cystic Fibrosis
Diabetes
Respiratory Conditions

18. Asthma
Asthma is a reversible inflammation of the airways that causes the bronchioles in the lungs to constrict, narrowing the airway.
Image:

19. Asthma Triggers Symptoms Allergens – Pollen, mold Wheezing
Drugs – Beta blockers, NSAIDs
Breathlessness
Environmental – smoke, cold air
Chest tightness
Respiratory Infections
Coughing
Depending on the person, they will either need to have just a rescue medication for the occasional asthma attack, or if someone is really sensitive to multiple triggers then they may need to have maintenance or controller therapy.

20. Short-acting beta-2 agonists (SABA)
Drug
Brand
Inhaler Type
albuterol
Ventolin HFA
Proventil HFA
ProAir HFA
pMDI
nebulizer
levalbuterol
Xopenex HFA
Used for an exacerbation
“Rescue Inhaler”
Mechanism
Beta-2 receptors on bronchial smooth muscles
Agonist = stimulation = Relaxation
Onset: 5-15min
Duration: 3-4 hrs
Drug Facts and Comparisons. [database online] St. Louis, MO: Wolters Kluwer Health, Inc.; 2016

21. Long-Acting beta-2 agonists (LABA)
Used for preventing an exacerbation
“Maintenance Inhaler”
Drug
Brand
Inhaler Type
Salmeterol
Serevent Diskus
DPI
Formoterol
Foradil Aerolizer
Mechanism
Same as SABA
e.g. Salmeterol
Peak Onset: 2-5 hours
Duration: 12 hours
Black Box Warning: monotherapy in asthma is contraindicated – increased risk of asthma-related deaths
Drug Facts and Comparisons. [database online] St. Louis, MO: Wolters Kluwer Health, Inc.; 2016

22. Corticosteroids “Maintenance Inhaler”
Mechanism:
Inhibit inflammatory response
Barnes PJ et al. Ann Intern Med. 2003; 129:

23. Corticosteroids Mechanism: Inhibit inflammatory response
First line for long-term control of asthma
Drug
Brand
Inhaler Type
Beclamethasone HFA
QVAR
pMDI – no need to shake
Budesonide
Pulmicort Flexhaler / Respules
DPI / nebulizer
Ciclesonide
Alvesco
Flunisolide HFA
Aerospan HFA
pMDI – built in spacer
Fluticsasone
Flovent HFA / Diskus
Anuity Ellipta
pMDI / DPI
DPI
Mometasone
Asmanex HFA / Twisthaler
Mechanism:
Inhibit inflammatory response
Decreased immune response
QVAR and Alvesco are the two inhalers that you do not need to shake and they are exceptions because they are not suspensions like the other pMDI
Technique:
Must rinse mouth and throat with water and spit out after use OR
Use a spacer device with pMDI
to prevent oral candidiasis (thrush)

24. Combination products = LABA + Steroid
Drug
Brand
Inhaler Type
Salmeterol +
Fluticasone
Advair HFA / Diskus
pMDI / DPI
Formoterol +
Budesonide
Symbicort
pMDI
Mometasone
Dulera
QVAR and Alvesco are the two inhalers that you do not need to shake and they are exceptions because they are not suspensions like the other pMDI
Combination Therapy AVOIDS LABA BBW
Black Box Warning: monotherapy in asthma is contraindicated – increased risk of asthma-related deaths

25. Chronic Obstructive Pulmonary Disease (COPD)
SMOKE
Cigarette
Noxious particles
Chemicals
Inflammation
Increased mucus production
Tissue damage
Chronic Inflammation
Airway narrowing
Fibrosis
Tissue Destruction
Emphysema
COPD is an irreversible inflammation of the airways that causes the bronchioles in the lungs to constrict, narrowing the airway.
COPD.Health Topics.NHLBI.NIH.Updated July 31, Accessed at:
Image:

26. COPD NOT shown to modify long-term progression
Drug Therapy
NOT shown to modify long-term progression
only decreases symptoms and/or complications
Inhalers used based on:
Symptoms
Degree of Airflow limitation
Spirometry
Risk of Exacerbations
Comorbidities
Symptoms
Dyspnea (Shortness of Breath)
Sputum Production
Chronic Cough
Smoking cessation is the only management that is proven to slow progression of COPD, drug therapy has not. It is only used to decrease symptoms and prevent complications

27. Vilanterol + Fluticasone
COPD Inhaler Therapy
Much of the same therapy for asthma is also used in COPD, with the short and long acting beta 2 agonists as well as the inhaled corticosteroids and the combination products. However a new class for COPD is the inhaled anticholinergics.
Vilanterol + Fluticasone
Aclidinium
Umecliinium
Taken from: Improving Outcomes in COPD Patients. Medscapre CME. 11/25/2010 Online at:

28. Anticholinergic Inhaler
Used for symptom control
Mechanism
Relax bronchial smooth muscle
Blocks action of acetylcholine
Systemic Anticholinergic Side Effects
Constipation
Blurred vision
Dry Eyes
Dry mouth
Urinary retention
Nasal congestion
Just as short acting and long acting beta agonists relaxed bronchial smooth muscle, so do inhaled anticholinergics just through another mechanisms
By blocking acetylcholine transmission in the lungs, bronchial smooth muscle is able to relax
Now acetylcholine is needed at other sites in the body and this is a prime example of how using a medication as an inhaler, that limits the absorption and therefore side effects at other sites in the body. By inhaling the anticholinergic we prevent or reduce.
Dry mouth is however a common side effect experienced with inhaler therapy, especially with Spririva, because we are not able to avoid exposure there.
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29. Anticholinergic Inhaler
Drug
Brand
Inhaler Type
Short-acting
Ipratropium
Atrovent HFA
pMDI & nebulizer
Ipratropium +
Albuterol
Combivent Respimat
DuoNeb
Respimat
Nebulizer
Long-acting
Aclidinium
Tudorza Pressair
DPI
Tiotropium
Spiriva Handihaler / Respimat
Umeclidinium
Incruse Ellipta
Just as short acting and long acting beta agonists relaxed bronchial smooth muscle, so do inhaled anticholinergics just through another mechanisms

30. Long-Acting beta-2 agonists (LABA) and Combination with Steroids
Drug
Brand
Inhaler Type
Approved for both asthma and COPD
Salmeterol
Serevent Diskus
DPI
Salmeterol +
Fluticasone
Advair HFA / Diskus
pMDI / DPI
Formoterol
Foradil Aerolizer
Formoterol +
Budesonide
Symbicort
pMDI
COPD Only
Arformoterol
Brovana
Nebulizer
Indacaterol
Arcapta Neohaler
Vilanterol +
Breo Ellipta
The same BBW for asthma does not exist for COPD in that monotherapy is NOT contraindicated and highlights different disease progressions between asthma and COPD
The same medications that are used in asthma can also be use in COPD, however there are more products available for COPD

31. Which of the following comes as a dry powdered inhaler?
Fluticasone/Salmeterol (Advair Diskus)
Albuterol HFA (ProAir HFA , Proventil HFA , Ventolin HFA )
Tiotropium (Spiriva Respimat )
Tiotropium (Spiriva Handihaler )
A & D
Correct Answer: E. A & D

32. Cystic Fibrosis (CF) Genetic disorder
Abnormal transport of chloride, bicarbonate, and sodium
Causes thick mucus production
Effects lungs
Difficulty breathing
Infections
(Also effects pancreas, liver, and intestines)
If you have CF, your mucus becomes thick and sticky. It builds up in your lungs and blocks your airways. (Airways are tubes that carry air in and out of your lungs.)
The buildup of mucus makes it easy for bacteria to grow. This leads to repeated, serious lung infections. Over time, these infections can severely damage your lungs.
Cystic Fibrosis.Health Topics.NHLBI.NIH.Updated Dec 26, Accessed at:
Image:

33. CF Inhaler Therapy
Bronchodilators
Mucolytics
Inhaled Antibiotics
For CF patients, the order of inhale medications is important.

34. CF Inhaler Therapy Opens the airway
Bronchodilators
Opens the airway
Used to facilitate the delivery of other inhaled medications
Mucolytics
Albuterol
Levalbuterol (Xopenex)
Ipratropium/albuterol (Combivent)
Bronchodilators like albuterol, levalbuterol, and combivent are not always used in CF patients to improve breathing directly like in asthma, but to ensure the airway is open and able to help the mucolytics get down into the lungs

35. CF Inhaler Therapy Hypertonic saline Dornase alfa (Pulmozyme)
Bronchodilators
Mucolytics
CF Inhaler Therapy
Hypertonic saline
Dornase alfa (Pulmozyme)
For CF patients, the order of inhale medications is important.
Recombinant human deoxyribonuclease 1
cleaves DNA – thins mucus
Produced by genetically engineered Chinese Hamster Ovary cells
Requires a jet nebulizer
Pulmozyme Package Insert, Genetech 2014
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36. CF Inhaler Therapy Inhaled Antibiotics
Most commonly CF patients have chronic Pseudomonas aeruginosa infections
For CF patients, the order of inhale medications is important.
Drug
Brand
Inhaler Type
Tobramycin solution
TOBI, Bethkis
nebulizer
Tobramycin powder
TOBI Podhaler
DPI
Aztreonam
Cayston
Top Image from: Sousa AM.. Pathogens. 2014; 3(3):60-703

37. Diabetes – Type 1 & 2 Peak Effect: Inhaled: 53 min SQ: ~1 hrs
Drug
Brand
Inhaler Type
Rapid-acting insulin
Afrezza
DPI
Peak Effect:
Inhaled: 53 min
SQ: ~1 hrs
Duration:
Inhaled: min
SQ: 2-4 hrs
Black Box Warning: risk of acute bronchospasm in patients with chronic lung disease – contraindicated in patients with asthma or COPD
Afrezza. Package Insert. Sanofi. 2014
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38. What the future may hold…
Future Inhaled Therapy
Vaccines
Antibodies
Hormones …
Ibrahim M. et al. Med Devices: Evidence and Research. 2015;8:131-9
Image from: