Professional Documents
Culture Documents
Chapter 8
Introduction
• Theophylline has been traditionally used to
treat asthma and chronic obstructive
pulmonary disease patients in both stable and
acute phases
• Mechanism of action of xantines is unclear
• Their clinical use has been relegated to that of
second or third-line agents
IDENTIFICATION
• Theophylline is related
chemically to the natural
metabolite xanthine,
which is a precursor of
uric acid
• Theophylline and
caffeine, because of their
methyl attachments,
these agents are often
referred to as
metylxanthines
Specific Xanthine Agents
• Natural Sources of Methylxanthines
– Theophylline
• tea leaves
– Caffeine
• tea leaves
• coffee beans
• kola nuts
• cocoa seeds
– theobromine
• cocoa seeds and beans
General Pharmacologic Properties
• Physiologic Effects of Xanthines
– CNS stimulation
– Cardiac muscle stimulation
– Diuresis
– Bronchial, uterine, and vascular smooth muscle
relaxation
– Peripheral and coronary vasodilation
– Cerebral vasoconstriction
• In clinical use, theophylline is classified as a
bronchodilator because it causes relaxation of
bronchial smooth muscle
Clinical Indications for Use of Xanthines
• Use in Asthma
– Sustained-release theophylline is indicated
as a long term controller drug, for
maintenance therapy of mild, persistent
(Step2) asthma or greater
– Sustained-release theophylline is
considered as a less-preferred alternative to
low-dose inhaled corticosteroids or
cromolyn-like agents as second-line
maintenance drug therapy in stable asthma
• Use in Chronic Obstructive Pulmonary Disease
– Xanthines would be considered for moderate
(Stage II) and severe (Stage III) COPD
– Recommended as an alternative to ß2 agonists or
anticholinergic agents
– Intravenous theophylline may be used in severe
exacerbations of COPD when aggressive inhaled
bronchodilator therapy is inadequate
• Use in Apnea of Prematurity
– Xanthines are first-line agents of choice to
stimulate breathing in apnea of prematurity
Mode of Action
• Theories of Activity
–Previously known as
phosphodiesterase inhibitors
• It was thought that xanthines caused
smooth muscle relaxation by inhibiting
phosphodiesterase, leading to an
increased level of cyclic AMP
• This theory has been questioned
– Other theories
• Antagonism of Adenosine
– may block smooth muscle constriction and mast
cell degranulation
• Catecholamine Release (epinephrine)
– xanthines may cause the production and release of
endogenous catecholamines leading to bronchial
relaxation
• Conclusion
– There is no accepted definitive explanation for the
action of xanthines to date
• There may be multiple mechanisms involved
Xanthine Derivatives
Xanthine Brand Names Formulations
Derivative
Theophylline Slo-phyllin, Theolair, Tablets, capsules,
Anhydrous Quibron-T, Dividose, syrup, elixir,
(100% Bronkodyl, extended-release
theophylline) Elixophyllin, Theo- tablets, capsules
Dur, Uni-Dur,
Uniphyl
Oxitriphylline Choledyl SA Tablets, syrup,
(64% theophylline) elixir, sustained-
release tablets