Drug Administration part V

Drug Administration by Inhalation
Inhalation in the form of an aerosol
, a gas, or a mist permits drugs to
be applied to the bronchial mucosa and,
to a lesser extent, to the alveolar membranes.
This route is chosen for drugs intended
to affect bronchial smooth muscle
or the consistency of bronchial mucus.
Furthermore, gaseous or volatile
agents can be administered by inhalation
with the goal of alveolar absorption
and systemic effects (e.g., inhalational
anesthetics, ). Aerosols are
formed when a drug solution or micronized
powder is converted into a mist or
dust, respectively.
In conventional sprays (e.g., nebulizer),
the air blast required for aerosol
formation is generated by the stroke of a
pump. Alternatively, the drug is delivered
from a solution or powder packaged
in a pressurized canister equipped
with a valve through which a metered
dose is discharged. During use, the inhaler
(spray dispenser) is held directly
in front of the mouth and actuated at
the start of inspiration. The effectiveness
of delivery depends on the position
of the device in front of the mouth, the
size of aerosol particles, and the coordination
between opening of the spray
valve and inspiration. The size of aerosol
particles determines the speed at which
they are swept along by inhaled air,
hence the depth of penetration into
the respiratory tract. Particles >
100 μm in diameter are trapped in the
oropharyngeal cavity; those having diameters
between 10 and 60μm will be
deposited on the epithelium of the
bronchial tract. Particles < 2 μm in diameter
can reach the alveoli, but they
will be largely exhaled because of their
low tendency to impact on the alveolar
epithelium.
Drug deposited on the mucous lining
of the bronchial epithelium is partly
absorbed and partly transported with
bronchial mucus towards the larynx.
Bronchial mucus travels upwards due to
the orally directed undulatory beat of
the epithelial cilia. Physiologically, this
mucociliary transport functions to remove
inspired dust particles. Thus, only
a portion of the drug aerosol (~ 10 %)
gains access to the respiratory tract and
just a fraction of this amount penetrates
the mucosa, whereas the remainder of
the aerosol undergoes mucociliary
transport to the laryngopharynx and is
swallowed. The advantage of inhalation
(i.e., localized application) is fully exploited
by using drugs that are poorly
absorbed from the intestine (isoproterenol,
ipratropium, cromolyn) or are subject
to first-pass elimination (beclomethasone
dipropionate, budesonide,
flunisolide, fluticasone dipropionate).
Even when the swallowed portion
of an inhaled drug is absorbed in unchanged
form, administration by this
route has the advantage that drug concentrations
at the bronchi will be higher
than in other organs.
The efficiency of mucociliary transport
depends on the force of kinociliary
motion and the viscosity of bronchial
mucus. Both factors can be altered
pathologically (e.g., in smoker’s cough,
bronchitis) or can be adversely affected
by drugs (atropine, antihistamines).