MDIs, nebulizers, and dry powder inhalers have evolved
in recent years. Each has advantages and drawbacks depending
on a multitude of factors.
Treating disease with inhaled
medications has a long tradition, dating back to at least 2000
BC, in India.1 The administration of medications by inhalation
provides an optimal delivery route for the treatment of both
pulmonary and nonpulmonary conditions. It generally requires
smaller doses, offers a rapid onset of drug action, and
reduces systemic effects compared with other routes of
administration.
Although bronchodilators are currently the most common
inhaled medication, many new classes of drugs (eg,
antibiotics, antioxidants, and anti-inflammatory agents) lend
themselves to administration via inhalation. In addition,
“medications aimed at systemic illnesses (eg, insulin, human
growth factor, and calcitonin) may also be administered as
aerosols, and are being shown to have reliable systemic
delivery through alveolar-capillary transport.”2
Nebulizers, metered dose inhalers (MDIs), and dry powder
inhalers (DPIs) have each found a niche in the quest for
optimal treatment and convenient use. While nebulizers have
evolved relatively independently of the drug formulations they
deliver, MDIs and DPIs have been developed for the specific
pharmaceutical being delivered.
The efficacy of inhaled medications may be affected by
patient age, severity of disease, inhalation technique, and
specific pharmacological properties of the drug. Oropharyngeal
deposition is a consistent confounding factor that continues
to challenge each delivery modality. Cost, convenience, and
ease of use also can affect patient compliance.
Selection of the optimal delivery device depends on the
drug to be administered, the age of the patient, and the
condition to be treated. Successful use of any inhaled
medication modality continues to be at least somewhat
dependent upon patient ability to use the device correctly.
The role of the respiratory therapist in patient education is
an essential element in that success.
Each delivery method has undergone significant improvements
and evolution, further impacted by specific Environmental
Protection Agency (EPA), Food and Drug Administration (FDA),
and Joint Commission on Accreditation of Healthcare
Organizations (JCAHO) requirements or recommendations. Based
on growing knowledge of pulmonary cell biology and
pathophysiology due to modern methods of molecular biology
research, the future characterization of pulmonary drug
transport pathways can lead to new strategies in aerosol drug
therapy.3
Nebulizers
Handheld nebulizers have
long provided a fast, efficient method of delivering
medications directly to the airways of the lungs. Conventional
nebulizers are highly inefficient because much of the aerosol
is wasted during exhalation. However, breath-assisted
nebulizers incorporating simple one-way valves can limit the
loss of aerosol during exhalation. Although they are
considerably more expensive than their disposable
counterparts, nondisposable nebulizers can deliver a higher
output in the therapeutic range, translating to measurably
superior particle deposition, and better outcomes confirmed by
both objective and subjective reports. These may become the
standard for home care use, and they offer an attractive
(though not inexpensive) alternative in the institutional
setting.
Several manufacturers have developed portable,
compressor-driven nebulizers to meet patient-driven need for
portability. Air compressors have a reputation for outstanding
long-term reliability, but designing a portable compressor
that is both lightweight and powerful has always been a
challenge.
Handheld ultrasonic nebulizers can produce a high output of
particles in the therapeutic range of 1 to 5 microns.4
Although they can be powered by a variety of electrical
sources, including alkaline batteries, and can be very compact
and lightweight, their relatively sophisticated design makes
it hard for them to surpass compressor-driven nebulizers for
long-term reliability. They have continued to evolve, becoming
smaller, lighter, and somewhat less expensive. Not all
medications are compatible with ultrasonic nebulizers.
Budesonide and dornase alfa are not approved for use in
ultrasonic nebulizers.
JCAHO and the FDA have both issued “strong recommendations”
to discontinue use of multi-dose bottled medications
traditionally used in nebulizers and replace them with
sterile, premixed, premeasured unit dose medications (UDMs).
There are three good reasons. First, the chemical benzal-
konium chloride, or BAC, an antibacterial agent added to
some bottled medications as a preservative, can cause airway
constriction, potentially blunting the effectiveness of the
drugs. Second, bottled, multi-dose medications can act as
vector, spreading infections; according to one pharmaceutical
representative, there have been reports of deaths from
nosocomial sepsis attributed to the use of multi-dose bottles.
Third, unit dose medications eliminate possible dosing errors
inherent when mixing each individual dose. It is possible to
inadvertently administer a nebulizer loaded only with
diluents, or containing a double dose of the medication when
using bottled multi-dose medications.
The move to replace multi-dose medications with UDMs has
been endorsed by the Institute for Safe Medication Practices
and the American Society of Health-System Pharmacists.
Metered Dose Inhalers
The development
of the metered dose inhaler was a response to a suggestion by
the 13-year-old asthmatic daughter of Dr George Maison, and it
received FDA approval in 1956.5 MDIs require a propellant to
deliver each puff, and the traditional propellant has been
chlorofluorocarbons (CFCs). To lower the risk of health and
environmental problems caused by ozone depletion and to help
restore the ozone layer, most countries have agreed to stop
using CFCs. The agreement, made in 1987, is known as the
Montreal Protocol.
The United States EPA subsequently mandated the
discontinuation of CFC propellants in MDIs due to their effect
on the earth’s ozone layer. Development of non-CFC propellants
has been reasonably successful, but the safety and
effectiveness of every new non-CFC inhaler must be reviewed by
the FDA before it is approved.
In 2002 the FDA published its final rule on “Use of
Ozone-Depleting Substances: Essential Use Determinations,”
which established the criteria under which CFC metered dose
inhalers would be deemed nonessential and removed from the US
market. Exceptions were made for MDIs for which a non-CFC
alternative was not available. However, the final rule also
specified that the FDA would evaluate the essentiality of any
remaining CFC MDIs available after January 1, 2005. In many
cases, pharmaceuticals that worked well with CFC propellants
were not compatible with their non-CFC counterparts. Some MDIs
using hydrofluoroalkane propellant already have been proven
safe and effective and have successfully been placed into use.
Complete elimination of all CFC propellants (there is
currently one exception still in use) is imminent.
Proper technique is essential for MDI effectiveness, and
several studies have shown an alarming lack of ability of
medical staff to correctly instruct patients in optimal
technique. In one study, for example, “only 5% used an MDI
perfectly. This improved to 13% after a lecture and
demonstration, and 73% after an intensive one-on-one
session.”6 Using MDIs with a holding chamber reduces the need
for patient coordination while increasing delivery of
medication to the airways and diminishing oropharyngeal
deposition by 10 to 15 times.
Dry Powder Inhalers
The first dry
powder inhalers, introduced in 1971, were slow to gain
acceptance. Due to the phaseout of CFC propellant inhalers and
improvements in DPI engineering, their acceptance and use have
increased exponentially. Salmeterol prescriptions via DPI, for
example, increased by 250% in 3 years, compared to the MDI
formulation.7
The ability of clinicians to properly instruct patients in
proper technique has been challenging with DPIs, just as it
has been with MDIs. A 1997 study showed that when tested for
MDI and DPI knowledge, RTs scored 67%, MDs scored 48%, and RNs
scored 39%. When demonstrating use, RTs scored only 60% on a
DPI device and MDs scored 21%.8 The pharmaceutical industry
has responded with improvements in DPI design, making the use
of current products much easier for clinicians to demonstrate
and for patients to use. Still essential to effective
medication delivery with DPIs is the patient’s ability to
generate sufficient inspiratory flow, and DPIs are not
recommended for patients with acute bronchospasm or children
under 6 years of age.4 However, the latest designs are able to
deliver therapeutic doses with much lower inspiratory flows
than previous designs required.9
Conclusion
For at least the past 30
years, marketplace competition to provide inhaled medications
that are more effective and easier and more convenient to use,
while minimizing side effects, has continuously evolved. More
recent awareness of environmental and infection control
concerns has spawned recommendations and regulations to
address the issues. The industry has embraced the challenges,
and the net result has been more and better tools for
providing optimal patient care. On the horizons are inhaled
medications that will need to be administered only once a day,
offering the utmost in convenience, and further enhancing
patient compliance.
John A. Wolfe, RRT, is a contributing writer to RT and
a member of the editorial advisory board.
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