EquipmentA metered dose inhaler (MDI) is a handheld aerosol device that uses a propellant to deliver the therapeutic agent. MDIs include a pressurized metal canister that contains the following [2, 12] :
The canister is housed in a plastic sleeve that has a mouthpiece for drug delivery. Actuation (ie, triggering of the canister) produces a fine atomized spray over 100-200 milliseconds that delivers the dose (the delivered dose varies with the particular medication). Most particles have high inertia, and most of the output at the orifice of the actuation consists of droplets that are large (25 microns) and have high velocities (30 m/s). [2, 8, 12, 13] This results in oropharyngeal deposition; only a minute fraction of the dose deposits in the lungs. [2, 8, 12] The pharmacologic agent in a suspension formulation results in a 10% respirable fraction; an agent in a dilute solution formulation with a volatile propellant blend may result in up to a 40% respirable fraction. The surfactant stabilizes the suspension by preventing caking. Various MDIs and an MDI diagram are shown in the images below.  Advantages of MDIs are as follows:
Disadvantages of MDIs are as follows:
Specific information regarding different MDIs and the amount of drug per actuation for each are provided in Table 1 below. Table 1. Metered Dose Inhalers (MDIs) and the Amount of Drug per Actuation (Open Table in a new window)
Subsequent to the Montreal Protocol on Substances that Deplete the Ozone Layer, chlorofluorocarbon (CFC) propellants (implicated in ozone depletion) have been phased out in favor of the organic compound hydrofluoroalkane (HFA), which is not known to cause ozone depletion. [15, 16] MDIs that use CFC have been replaced by those that use HFA-134a. [17, 18] These new devices are not only more environmentally friendly but, surprisingly, are also more effective. The HFA propellant produces an aerosol with smaller particle size, resulting in improved deposition in the small airways and greater efficacy at equivalent doses compared with CFC MDIs. The United States Food and Drug Administration (FDA) published an update in 2010 regarding the progress that the US was making with its obligations under the Montreal agreement. [17] Seven MDIs that contain CFCs were still on the US market at that time, but they have been phased out. Alternatives to some of these medications (eg, dry powder formulations) are available. For additional information, see the FDA website. Dry powder inhalersA dry powder inhaler (DPI) is a breath-actuated device that delivers the drug in the form of particles contained in a capsule or blister that is punctured prior to use. [19] This type of inhaler requires an adequate inspiratory flow rate for drug delivery, as it does not include a propellant. [20] Because of this inspiratory flow rate requirement, DPIs are not appropriate for treatment of acute asthma attacks. The degree of resistance to inspiratory flow required to aerosolize the medication varies with each of the multiple versions of DPIs. [9] Low-resistance devices are suitable for the treatment of children and those with decreased lung function (forced expiratory volume in 1 second [FEV1] < 30% of predicted), [21] whereas high-resistance devices require a higher inspiratory flow rate to aerosolize an equivalent drug dose. For a comparison of DPI drug delivery amounts, see Table 2 below. Table 2. Dry Powder Inhalers (DPIs) (Open Table in a new window)
DPI devices include the following (also see the images below):
The Diskus (eg, Advair, Flovent), shown below, is a blister pack, unit-dose device. The pack consists of a coiled, double-foil strip of 60 blisters, each containing one dose of drug powder with a lactose carrier. [9] The drug dose for this device ranges widely (50-500 mcg), depending on the product. During inhalation, each blister is moved into place and its lid-foil is peeled away by a contracting wheel. The inhaled air is drawn through the opened blister, aerosolizing and delivering the dose through the mouthpiece. [21] An Aerolizer inhaler, shown below, is a device used for formoterol fumarate (Foradil) inhalation, a long-acting selective beta2-adrenergic agonist. [22] To use, a formoterol capsule is placed in the Aerolizer inhaler well, and the capsule is pierced by pressing and releasing the button on the side of the device. This permits the formoterol fumarate formulation to disperse into the air stream when the patient inhales rapidly and deeply through the mouthpiece. [23] HandiHaler, depicted in the image below, is an inhalation device used to deliver the dry powder tiotropium bromide (Spiriva), a long-acting anticholinergic agent. [24] The tiotropium capsule is placed in the center chamber of the HandiHaler, and the capsule is pierced by pressing and releasing the green button. This leads to the dispersal of tiotropium formulation into the air stream when the patient inhales through the mouthpiece. A Twisthaler, shown below, is an inhalation device that delivers the fine dry powder mometasone furoate (Asmanex), an inhaled corticosteroid. [9] The Flexhaler, depicted below, is an inhalation device used to deliver the dry powder budesonide (Pulmicort), an anti-inflammatory synthetic corticosteroid. The Flexhaler has replaced the Turbuhaler, which is no longer marketed. The budesonide capsule is placed in the center of the chamber of the Flexhaler, and the capsule is pierced by twisting the device fully one way and then back fully the other way. This allows the budesonide formulation to disperse into the air stream when the patient inhales rapidly and deeply through the mouthpiece. DPI advantages include the following:
DPI disadvantages include the following:
Inhalation accessory devicesInhalation accessory devices (IADs) generally fall into 2 categories: spacers and holding chambers. Using a spacer device with an MDI can help reduce the amount of drug that sticks to the back of the throat, improving direction and deposition of medication delivered by MDIs. Spacers and holding chambers extend the mouthpiece of the inhaler and direct the mist of medication toward the mouth, reducing medication lost into the air. SpacersA spacer, shown below, is an extension add-on device that permits the aerosol plume from the MDI to expand and slow down, turning it into a very fine mist instead of a high-pressure actuation spray. The cloud of vapor is so fine that most patients do not feel or taste it as they breathe it in. The fine drug particles are carried deep into the lung, where they are most effective, instead of hitting the tongue or the back of the throat the way a blast from an MDI sometimes does. [6, 25] Spacers attempt to address the problem of patient coordination between device actuation and breath. When using a spacer, however, the patient must still coordinate the breath to occur slightly before actuation. [10, 26] For information on features of particular spacers, see Table 3 and Table 4 below. Table 3. Open Tube Spacers (Open Table in a new window)
Table 4. Reverse-Flow Spacers (Open Table in a new window)
Valved holding chambersValved holding chambers (VHCs) allow for a fine cloud of medication to stay in the spacer until the patient breathes it in through a one-way valve, drawing the dose of medicine into the lungs. Examples include Aerochamber and Optichamber. For more information on VHC features, see Table 5 below. Use of a spacer or VHC is recommended with inhaled corticosteroids to minimize such effects as thrush and hoarseness. [7] Children aged 4 years or younger should use a VHC with a mask. [7] Table 5. Valved Holding Chambers (VHCs) (Open Table in a new window)
Advantages of IADs are as follows:
Disadvantages of IADs are as follows:
NebulizersNebulizers are devices that transform solutions or suspensions of medications into aerosols that are optimal for deposition in the lower airway. This mode of aerosol drug delivery is critical for respiratory disorders and may include corticosteroids, bronchodilators, anticholinergics, antibiotics, and mucolytic agents. Inhalation solution doses are shown in Table 6. Table 6. Inhalation Solutions Often Used with Nebulizers (Open Table in a new window) Nebulization provides a vehicle for drug delivery to patients who are too ill or too young to use other portable inhaler devices. [11] The 2 types of nebulizers are pneumatic jet nebulizers and ultrasonic nebulizers. A pneumatic jet nebulizer (see images below) delivers compressed gas through a jet, causing an area of negative pressure and drawing the liquid up the tube by the Bernoulli effect. The solution is entrained into the gas stream and then sheared into a liquid film that is unstable and is broken into droplets by surface tension forces. The fundamental concept of nebulizer performance is the conversion of the medication solution into droplets in the respirable range of 1-5 micrometers. [27] An ultrasonic nebulizer generates high-frequency ultrasonic waves (1.63 MHz) from electrical energy via a piezoelectric element in the transducer. These ultrasonic waves are transmitted to the surface of the solution to create an aerosol. Aerosol delivery is by a fan or the patient’s inspiratory flow; particle sizes may be larger with this device. A limitation of ultrasonic nebulizers is that they do not nebulize suspensions efficiently. [11] Ultrasonic nebulizers may be used with all nebulized medications except Pulmicort Respules suspension (most nebulized medications are solutions). Pulmicort Respules cannot be used with nebulizer units that generate heat, as is the case with most ultrasonic nebulizers (with the exception of the Omron MicroAir). The following are advantages of nebulizers:
The following are disadvantages of nebulizers:
PositioningMDIs, DPIs, and nebulizers are used with the patient sitting up comfortably straight. |
For which of the following reasons should a client attach a spacer to a meter dosed inhaler?
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