Page 461 - Clinical Application of Mechanical Ventilation

Pharmacotherapy for Mechanical Ventilation 427

Adverse Effects. When inhaled, atropine is readily distributed throughout the body
and may cause systemic effects such as tachycardia, nervousness, headache, and
dried secretions. Atropine easily penetrates the blood-brain barrier and at higher
levels may cause hallucination or mental confusion. Patients with atropine-induced
hallucinations have been erroneously diagnosed with psychiatric disorders.
Other anticholinergic agents such as ipratropium bromide (Atrovent) and glycopyr-
rolate (Robinul, an atropine derivative) are not well absorbed systemically and, when
inhaled, produce fewer adverse effects than those produced by atropine. Drying of
secretions is an adverse effect of Atrovent, but it can be prevented by proper humidi-
fication or systemic hydration.

Clinical Considerations. Ipratropium bromide is not indicated for the initial treatment
of acute episodes of bronchospasm where immediate response is required. These
agents are commonly used in addition to the rapid-acting beta agonists. For ex-
ample, ipratropium bromide is premixed with albuterol sulfate for MDI use (Com-
bivent). The normal dosage is 2 puffs of this mixture QID.

Xanthine Bronchodilators

The third class of bronchodilators, the xanthines, include the drugs theophylline
xanthine bronchodilators:
Drugs that produce bronchodila- and its salt form aminophylline. Theophylline is a stimulant found in tea leaves
tion by inhibiting phosphodies- and is chemically related to other stimulants found in coffee and colas. Because
terase, an enzyme that inactivates
cyclic 3’5’ AMP (a substance of the structural similarity of caffeine and theophylline, they share effects such as
that promotes bronchodilation). tachycardia, central nervous stimulation (wakefulness), and diuresis (and potential
Examples are oral theophyl-
line (Theo-Dur, Slo-bid) and for dysrhythmia). Caffeine is a xanthine that produces similar effects to theophyl-
aminophylline, a water-soluble line but works through somewhat different mechanisms and therefore can have an
theophylline (Aminophyllin,
Somophyllin). additive effect (caffeine is included in aminophylline solution).
Xanthines are used for their relaxing effects on smooth muscles and ability to
inhibit inflammation; however, be aware that in some individuals theophylline may
Pulmonologists often aggravate bronchospasm because it can lower esophageal pressure, which may lead
refer to theophylline as “Dig- to reflux. Clinically, the xanthines are considered to be less effective in acute bron-
(digitalis)for the diaphragm,”
meaning that what digoxin chospasm than the beta agonists and are more useful in the management of inflam-
does for heart contractil- mation associated with asthma and COPD. For individuals with carbon dioxide
ity, theophylline does for
diaphragm contracticility. retention, xanthines improve ventilation by heightening carbon dioxide sensitivity
in the central nervous system and enhancing diaphragmatic contractility.
Water-soluble aminophylline is suitable for intravenous administration and may
be indicated as an add-on therapy for acute bronchospasm (Cottrell et al., 1995).
Table 13-5 lists the oral and intravenous xanthine bronchodilators. Theophylline’s
ability to enhance diaphragm contractility and respiratory drive are of primary con-
cern for COPD patients, but there is renewed interest in the drug for asthmatic
patients, particularly for its potential to reduce airway inflammation.
Mechanism of Action. Multiple theories on the mechanism of theophylline have
been described. One generally accepted mechanism is that theophylline produces
bronchodilation by inhibiting phosphodiesterase (PDE). Recall that PDE rapidly
inactivates cyclic 3′5′ AMP, the substance that relaxes the airway smooth muscles

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