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Bronchodilators |   |
Theophylline
Theophylline has more than twenty different trade names, including: (Aerolate, Aquaphyllin, Bronkodyl, Slo-bid Gyrocaps, Theon, Respbid, and Theolair). It is related chemically to the natural metabolite xanthine, which is a precursor of uric acid. Xanthines have a wide variety of physiologic effects on humans, ranging from CNS stimulation to bronchial smooth muscle relaxation and cerebral vasoconstriction. The effects of xanthines are well known to people who drink caffeinated beverages like coffee, colas, and tea.
Theophylline is available in liquid, tablet, and capsule form. Aminophylline delivered via aerosol has been tested for treating asthmatic patients and most of the evidence indicated that it has minimal impact on forced expiratory flow rates in patients with acute obstructive disorders. It also was found to irritate the pharynx, caused coughing and wheezing, and had a very bitter taste.
While the exact mechanism of action of xanthines, particularly theophylline, remains relatively unknown, they have had a variety of clinical uses. Traditionally, theophylline has been used in the management of asthma and COPD. While it is usually classified as a bronchodilator, theophylline is relatively ineffective when compared with the beta agonists.
Recent clinical findings have shown that its use provides no additional benefit when patients have already been treated with intravenous steroids and inhaled beta adrenergic bronchodilators. The NIH's 1997 Guidelines for Diagnosis and Management of Asthma do not indicate theophylline as first line therapy for the pharmacologic management of asthma and COPD. However, theophylline remains very popular and effective, although its use is frequently being relegated to a secondary or tertiary role after beta agonists, inhaled steroids, or mediator agents.
Besides its use for bronchodilation, theophylline has been shown to increase patient's minute volume by improving contractility of a normal or fatigued diaphragm. Because it stimulates the phrenic nerve, theophylline has proven useful in reducing the severity of sleep apnea in adults and apnea in neonates. However, because there is little difference between dose and serum levels that provide therapeutic benefit and those which cause toxicity (a narrow TI), theophylline has a wide variety of potential side effects throughout the body's organ systems, including:
- Central nervous system--headache, anxiety, insomnia, restlessness, tremor, and convulsions
- Gastrointestinal system--nausea, vomiting, abdominal pain, diarrhea, hematemesis, gastroesophageal reflux, and anorexia
- Respiratory system--tachypnea
- Cardiovascular system--hypotension, palpitations, supraventricular tachycardia, ventricular arrhythmias
- Renal system--diuresis
Proper dosing of theophylline is complicated because of the variability in the rate at which individuals metabolize it. Different forms of the drug are not always equivalent, and there are a variety of factors that can affect the half-life of theophylline. This includes cigarette or marijuana smoking, high caffeine intake, barbiturate use, high protein diets, liver disease, marked obesity, severe hypoxemia, or fever. As a result, dosing schedules, which are available in product literature and references such as the Physician's Desk Reference, are used to titrate the drug. It is recommended that these tables be consulted when administering theophylline for different ages and clinical applications.