Xanthine drugs are a class of medications commonly used to treat respiratory conditions. These drugs work by relaxing the muscles around the airways, making it easier to breathe.
Derived from naturally occurring compounds, xanthines have been a cornerstone of respiratory therapy for decades.
In this article, we will explore how xanthine drugs work, their common uses, potential side effects, and important considerations for patients and healthcare providers.
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What Are Xanthine Drugs?
Xanthine drugs are a group of medications derived from xanthine, a naturally occurring compound found in the body and in certain foods like coffee and tea. These drugs act as bronchodilators, meaning they relax and open the airways in the lungs, making breathing easier. They are primarily used to treat respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and bronchitis.
The most common xanthine drugs include theophylline, aminophylline, and caffeine. These medications work by blocking the action of an enzyme called phosphodiesterase, which leads to relaxation of airway muscles and reduction of inflammation. In addition to their respiratory benefits, some xanthine drugs have stimulant effects on the central nervous system, increasing alertness and reducing fatigue.
Despite being effective, xanthine drugs are less commonly used today due to the availability of newer medications with fewer side effects. However, they remain a valuable treatment option in certain cases, particularly when other treatments are not suitable.
Types of Xanthine Drugs
Xanthine drugs are a class of medications known for their bronchodilatory and stimulant effects. There are four primary types of xanthine drugs, including:
- Theophylline
- Aminophylline
- Theobromine
- Caffeine
Each of these drugs has a unique chemical structure, leading to distinct effects on the body, ranging from respiratory relief to central nervous system stimulation.
Theophylline
Theophylline is the most commonly prescribed xanthine drug and is frequently used to manage asthma, COPD, and other respiratory conditions involving airway obstruction. It works by relaxing the smooth muscles in the airways, helping to prevent wheezing, chest tightness, and shortness of breath.
Additionally, theophylline has anti-inflammatory properties, reducing swelling and mucus production in the airways. It is typically administered orally or through sustained-release formulations to ensure consistent therapeutic effects.
Aminophylline
Aminophylline is a compound closely related to theophylline, consisting of theophylline combined with ethylenediamine to improve its solubility. It serves as a bronchodilator by relaxing airway muscles, allowing for easier breathing.
Aminophylline is often administered intravenously in emergency situations, such as severe asthma attacks, when rapid bronchodilation is needed. Its quick action makes it particularly valuable in critical care settings.
Theobromine
Theobromine, found naturally in cocoa and chocolate products, is another xanthine derivative with bronchodilatory effects. Though less potent than theophylline, it can still help relax the muscles of the respiratory tract, easing breathing difficulties.
In addition to its respiratory benefits, theobromine has mild stimulant effects and can reduce coughing by suppressing the cough reflex.
Caffeine
Caffeine is perhaps the most well-known xanthine drug due to its widespread use as a stimulant. It has several pharmacological effects, including bronchodilation, making it beneficial for certain respiratory conditions.
Studies have shown that caffeine can reduce respiratory muscle fatigue, enhance breathing efficiency, and alleviate mild asthma symptoms. It is sometimes used in neonatal care to treat apnea of prematurity in infants, helping to stimulate regular breathing patterns.
Note: Xanthine drugs play a crucial role in respiratory therapy due to their ability to relax airway muscles and improve breathing. Understanding the unique properties of theophylline, aminophylline, theobromine, and caffeine can guide effective treatment strategies for various respiratory conditions.
Xanthine Drugs Practice Questions
1. What are xanthines?
Xanthines, also known as methylxanthines, are secondary or “side-door” bronchodilators used to manage respiratory conditions.
2. What are some examples of xanthines?
Theophylline, caffeine, and theobromine.
3. What are the uses of xanthines?
Management of asthma, COPD, and apnea of prematurity.
4. What is caffeine citrate?
The drug of choice for treating apnea of prematurity due to its safety and effectiveness.
5. What are the effects of xanthines?
CNS stimulation, smooth muscle relaxation, diuresis, and cerebral vasoconstriction.
6. What are the serum levels of theophylline?
5-10 mcg/mL for COPD, 5-15 mcg/mL for asthma, and generally kept below 20 mcg/mL.
7. What are the side effects of xanthines?
Nausea, vomiting, diuresis, hypotension, cardiac arrhythmias, headaches, and tremors.
8. What is the therapeutic range of theophylline?
10-20 mcg/mL
9. What are the three bronchodilators used for the lower respiratory tract?
Xanthine derivatives, sympathomimetics/beta-adrenergic agonists, and anticholinergics.
10. What do xanthine drugs do?
Xanthines directly relax the smooth muscles of the respiratory tract and blood vessels, providing relief from asthma symptoms and preventing bronchospasms.
11. What is the prototype for xanthines?
Theophylline (Slo-Bid, Theo-Dur) and aminophylline (Somophylline) for IV use.
12. What are xanthines primarily used for?
They are used for preventing asthma symptoms, relieving acute asthma attacks, and treating chronic respiratory conditions. They are absorbed through the GI tract and can be taken with food.
13. What are the major adverse effects of xanthines?
GI: Nausea, vomiting, diarrhea, and anorexia (early signs of toxicity); Cardiovascular: Tachycardia, dysrhythmias, angina, hypotension, palpitations; CNS: Seizures and tremors (late signs of toxicity).
14. What is caused by xanthines that resemble adrenergic medications?
Neurologic stimulation, including increased heart rate and alertness.
15. What is the serum level of theophylline?
10-20 mcg/mL
16. Why are levels drawn at the first dose when taking xanthine?
There is no specific antidote for theophylline overdose, so standard emergency measures such as activated charcoal, gastric lavage, and emesis must be used if toxicity occurs.
17. What should be monitored when taking xanthines?
Monitor heart rate (HR), respiratory rate (RR), blood pressure (BP), and ECG for rhythm changes due to potential cardiovascular stimulation.
18. How are xanthines used in asthma?
Theophylline is used as maintenance therapy for asthma in patients older than 5 years.
19. How are xanthines used in COPD?
Theophylline is recommended as an alternative to beta-2 agonists and anticholinergics but should not be used during acute exacerbations.
20. How are xanthines used in apnea of prematurity?
They are the first-line treatment. Theophylline has been used extensively, but caffeine citrate is preferred due to its safer profile and higher therapeutic index.
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21. Where does theophylline come from?
Tea leaves
22. Where does theobromine come from?
Cocoa seeds or beans
23. What are the effects of xanthines on humans?
CNS stimulation, cardiac muscle stimulation, diuresis, bronchial, uterine, and vascular smooth muscle relaxation (theophylline is classified as a bronchodilator), peripheral and coronary vasodilation, and cerebral vasoconstriction (used in headache remedies).
24. Why do we titrate theophylline doses?
Individuals metabolize theophylline at different rates, making it challenging to determine the correct therapeutic dose.
25. What is the therapeutic action of xanthines?
They relax the smooth muscles of the respiratory tract, promoting bronchodilation.
26. What is the pharmacokinetics of xanthines?
They are rapidly absorbed from the GI tract, widely distributed, metabolized in the liver, and excreted in the urine.
27. What are the adverse effects of xanthines?
Theophylline levels can cause GI upset, irritability, tachycardia, seizures, brain damage, and even death when toxic levels are reached.
28. What are the contraindications for xanthines?
GI disorders, coronary artery disease, respiratory dysfunction, renal or hepatic disease, alcoholism, and hyperthyroidism.
29. What is theophylline?
Brand Names: Theochron, Elixophyllin, Theo-24; Formulations: Tablets, capsules, syrup, elixir, extended-release tablets, capsules, and injections.
30. What is oxtriphylline?
Brand Name: Choledyl SA; Formulations: Tablets, syrup, elixir, and sustained-release tablets.
31. What is aminophylline?
Brand Name: Aminophylline; Formulations: Tablets, oral liquid, injection, and suppositories.
32. What is dyphylline?
Brand Name: Lufyllin; Formulations: Tablets and elixir.
33. What are some common side effects of xanthines?
Gastric upset, headache, anxiety, irritability, tachycardia, seizures, and diuresis.
34. How are xanthines commonly used in apnea of prematurity?
Caffeine citrate is preferred over theophylline. The loading dose is 20 mg/kg, followed by 5 mg/kg daily.
35. What is the rapid theophyllinization dosage?
Oral loading dose of 5 mg/kg of ideal body weight.
36. What is the slow theophyllinization dosage?
An initial dose of 16 mg/kg/24 hr or 400 mg/24 hr, whichever is lower.
37. What is a methylxanthine (xanthine)?
They are inhibitors that indirectly increase the amount of cAMP in smooth muscles, causing bronchodilation. They are administered via tablets, IV, or injection.
38. What is apnea of prematurity?
A condition where premature infants experience periodic pauses in breathing due to immature respiratory control systems.
39. What are the two main drug classifications of xanthines?
Theophylline and caffeine.
40. What are some of the physiologic effects of xanthines that have stimulant properties?
CNS stimulation, cardiac muscle stimulation, bronchial smooth muscle relaxation, cerebral vasoconstriction, and diuresis.
41. What is the safe therapeutic blood level of theophylline?
10-20 mcg/mL to optimize bronchodilation.
42. What level should theophylline be kept at for neonates and children?
5-10 mcg/mL
43. When can theophylline toxicity occur?
When the serum level exceeds 20 mcg/mL.
44. What are the signs of theophylline toxicity?
Tremors, nausea, vomiting, seizures, tachycardia, and arrhythmias.
45. What examples are theophylline and caffeine?
Methylxanthines
46. What condition do premature neonates use theophylline and caffeine to treat?
Apnea of prematurity
47. If a COPD patient is using Combivent and is also taking inhaled corticosteroids, what could be recommended as long as the patient is not experiencing an acute exacerbation?
Theophylline
48. What type of drugs are xanthines?
They are considered third-line or alternative respiratory drugs.
49. What is the mechanism of action of xanthines?
The exact mechanism is unclear, but they are thought to cause bronchodilation through various physiological pathways.
50. What are alkaline substances from plants that react with acids to form salts?
Alkaloids
51. What are drugs derived from xanthines?
Methylxanthines
52. What enzyme changes intracellular signaling?
Phosphodiesterase
53. What is the xanthine of choice to treat apnea of prematurity in neonates?
Caffeine citrate
54. If you are working in the neonatal intensive care unit and discover your patient has apnea of prematurity, you should suggest a plan for dosing what?
Caffeine citrate
55. How does caffeine citrate work in infants?
It stimulates breathing by activating the central nervous system and has a high therapeutic index with fewer side effects than theophylline.
56. Why is theophylline classified as a bronchodilator?
It relaxes bronchial smooth muscles, allowing easier airflow.
57. What are the three main physiological effects produced by xanthines?
Cardiac muscle stimulation, central nervous system stimulation, and bronchial smooth muscle relaxation.
58. What are three possible theories explaining how theophylline works?
Inhibition of phosphodiesterase, antagonism of adenosine, and stimulation of catecholamine release.
59. What two things are stimulated by caffeine?
Skeletal muscles and the central nervous system.
60. Why is it difficult to determine the therapeutic doses of theophylline?
Because individuals metabolize theophylline at different rates, making dosage adjustments challenging.
61. What is 5 mg/kg known as?
Ideal body weight dosing for theophylline.
62. What is 100% theophylline known as?
Anhydrous theophylline
63. What is the current recommended blood serum theophylline level for the management of asthma?
5-15 mcg/mL
64. What is the current recommended blood serum theophylline level for the management of COPD?
5-10 mcg/mL
65. How is the dosage of theophylline best monitored?
By measuring serum drug levels.
66. What is a significant side effect of theophylline?
Nausea
67. What includes less toxic side effects of theophylline therapy?
Headache, diuresis, tachypnea, palpitations, and vomiting.
68. What will cause an increase in blood theophylline levels?
Renal failure
69. What three conditions increase theophylline blood levels?
Pneumonia, corticosteroid use, and beta-blocker therapy.
70. What are five disadvantages of theophylline therapy?
Narrow therapeutic margin, toxic effects, unpredictable blood levels, need for individual dosing, and numerous drug-drug and drug-condition interactions.
71. What are five factors that will increase theophylline levels?
Alcohol, beta-blocking agents, zileuton, calcium channel blockers, and the influenza virus vaccine.
72. What are three factors that will decrease theophylline levels?
Isoniazid, loop diuretics, and rifampin.
73. What two things does theophylline increase within respiratory muscles?
Strength and endurance
74. What are the three anti-inflammatory effects of theophylline?
Decreased migration of activated eosinophils into bronchial mucosa, inhibition of pro-inflammatory cytokines, and reduced airway responsiveness to stimuli such as histamine and methacholine.
75. What are the four main side effects of theophylline?
Restlessness, supraventricular tachycardia, hypotension, and nausea.
76. What four things does theophylline produce within the body?
Increased phrenic nerve activity, anti-inflammatory effects, increased ventilatory drive, and increased respiratory rate.
77. Is caffeine a type of methylxanthine drug?
Yes, it is.
78. When are methylxanthine drugs effective in treating infants?
They are effective in treating infants with poor respiratory drive and those with low birth weights.
79. What are the side effects of methylxanthines?
Nausea, anxiety, tremors, arrhythmias, and seizures.
80. What are the recommended levels of serum theophylline?
8-10 mcg/mL
81. What is the primary mechanism of action for xanthine drugs?
Inhibition of phosphodiesterase, leading to increased cyclic AMP (cAMP) levels and bronchodilation.
82. What is the role of cAMP in the respiratory system?
It relaxes bronchial smooth muscles, reducing airway resistance and improving airflow.
83. How do xanthines affect cardiac function?
They stimulate the heart, increasing heart rate and contractility.
84. What is the relationship between xanthines and diuresis?
Xanthines increase urine production by promoting diuresis through kidney stimulation.
85. What enzyme do xanthine drugs inhibit to increase cAMP?
Phosphodiesterase
86. What is the effect of xanthines on cerebral blood flow?
They cause cerebral vasoconstriction, which can reduce headaches.
87. How are xanthines metabolized in the body?
They are metabolized in the liver through the cytochrome P450 enzyme system.
88. How are xanthines excreted from the body?
Primarily through the urine as active or inactive metabolites.
89. What is a major therapeutic use of caffeine citrate in neonates?
Treatment of apnea of prematurity by stimulating the central nervous system.
90. Why is theophylline considered a “second-line” drug in asthma management?
Due to its narrow therapeutic window, potential toxicity, and better alternatives like inhaled corticosteroids and beta-agonists.
91. What is the typical half-life of theophylline in healthy adults?
Approximately 8-12 hours, depending on individual metabolism.
92. How does smoking affect the metabolism of xanthines?
Smoking induces liver enzymes, increasing the metabolism of theophylline and reducing its effectiveness.
93. What dietary products contain natural xanthines?
Coffee, tea, chocolate, and some energy drinks.
94. Why are xanthines not recommended for use during acute asthma exacerbations?
Their onset of action is too slow for emergency bronchodilation.
95. What are the therapeutic indications for aminophylline?
Management of asthma, COPD, and bronchospasm in acute respiratory conditions.
96. Why must serum theophylline levels be monitored frequently?
To avoid toxicity due to its narrow therapeutic window.
97. What drug interactions increase the risk of theophylline toxicity?
Fluoroquinolone antibiotics, cimetidine, and oral contraceptives.
98. How do xanthines affect the respiratory drive?
They increase the respiratory drive by stimulating the medullary respiratory centers.
99. Why is caffeine citrate preferred over theophylline in neonatal care?
Caffeine citrate has a wider therapeutic index, longer half-life, and fewer side effects.
100. What are early signs of theophylline toxicity to monitor in patients?
Restlessness, tremors, nausea, vomiting, and insomnia.
Final Thoughts
Xanthine drugs play a vital role in managing respiratory conditions by helping to improve breathing and reduce symptoms associated with obstructive lung diseases.
While their use has declined due to the development of newer medications, they remain an effective option for many patients.
Understanding how these drugs work, along with their potential side effects and proper usage, can empower patients and healthcare providers to make informed decisions about respiratory treatment plans.
Written by:
John Landry is a registered respiratory therapist from Memphis, TN, and has a bachelor's degree in kinesiology. He enjoys using evidence-based research to help others breathe easier and live a healthier life.
References
- Faarc, Gardenhire Douglas EdD Rrt-Nps. Rau’s Respiratory Care Pharmacology. 10th ed., Mosby, 2019.
- Faarc, Kacmarek Robert PhD Rrt, et al. Egan’s Fundamentals of Respiratory Care. 12th ed., Mosby, 2020.
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
- Seddon P, Bara A, Ducharme FM, Lasserson TJ. Oral xanthines as maintenance treatment for asthma in children. Cochrane Database Syst Rev. 2006.
- Welsh EJ, Bara A, Barley E, Cates CJ. Caffeine for asthma. Cochrane Database Syst Rev. 2010.