Page 462 - Clinical Application of Mechanical Ventilation

428 Chapter 13

TABLE 13-5 Xanthine Bronchodilators

Generic Name Trade Names Administration

Theophylline (100% anhydrous) (Aerolate, Constant-T, Respbid, Slo-bid, Oral, IV
Theo-Dur, Uniphyl)
Aminophylline (78–86% (Aminophyllin, Somophyllin) Intravenous
theophylline, water soluble)
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and inhibits mast cell histamine release. By inhibiting PDE, xanthine indirectly
increases cyclic 3′5′ AMP levels. A second theory describes theophylline as an

Inhibition of phosphodi- adenosine antagonist. Normally, the stimulation of adenosine receptors results
esterase, acting as an adenos- in histamine release, thus a blocking effect provides anti-inflammatory benefits.
ine antagonist, and increased
catecholamine release are And finally, theophylline has been shown to increase catecholamine release in
three proposed mechanisms some studies. The enhanced sympathomimetic-like adverse effects experienced
of action of theophylline.
with a nonautonomic drug such as theophylline seems to support this finding
(Gardenhire, 2007).
Adverse Effects. Unlike the adrenergic and anticholinergic bronchodilators, xan-
thines are not useful via inhalation due to their lack of ability to penetrate the mu-
cosal lining of the airways. Xanthines are available for systemic administration via
the intravenous and oral routes and, thus, they produce widespread effects.
Some of the adverse effects (tachycardia and skeletal muscle and CNS stimula-
tion) can occur even at therapeutic serum theophylline ranges of 5–15 mcg/mL.
Routine monitoring of serum theophylline levels is one way to prevent these effects
from intensifying to the degree of toxicity. However, the practitioner should be able
to recognize the early warning signs of theophylline toxicity since a narrow margin
between therapeutic and toxic levels exists. Patients with mild to moderate toxic-
ity (20 to 30 mcg/mL) may experience tachypnea, palpitations, nausea, vomiting,
headache, and agitation. Severe toxicity (. 40 mcg/mL) is marked by gastric bleed-
ing, arrhythmias, and seizures (Wilkins et al., 2008; Witek, 1994).

Clinical Considerations. Nausea, vomiting, abdominal pain, diarrhea, and nervous-
Nausea, vomiting,
abdominal pain, diarrhea, and ness are some initial signs of theophylline toxicity. These signs may not be apparent
nervousness are some initial in or communicated by the sedated or paralyzed patient. If xanthines are used in a
signs of theophylline toxicity.
paralyzed patient, the serum theophylline level should be monitored closely to pre-
vent inadvertent overdose. Toxic adverse effects of theophylline can be minimized
when the serum theophylline level is maintained within its therapeutic range of
Adverse effects of 5–15 mcg/mL (NIH Publication, 1997).
theophylline can be mini-
mized by keeping the serum Most of the theophylline is metabolized by the liver and excreted in the urine.
theophylline level from 5 to
15 mcg/mL. Patients at risk for theophylline toxicity are those with heart failure or liver disease.
Diminished liver perfusion (due to heart failure) or impaired liver function can re-
duce the metabolism and clearance rate of theophylline. The end result is excessive
theophylline accumulation and toxicity.
On the other hand, patients at risk for inadequate theophylline are those who
smoke. Smoking increases the level of hepatic enzyme and theophylline clearance.

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