Plants Used for Respiratory Problems - II

1. Plants Used for Respiratory Problems - II Theophylline

2. Two types of bronchodilators • Adrenergic agents • Increase the volume and diameter of bronchial smooth muscles by relaxing them • Include norepinephrine, epinephrine, and ephedrine • Theophylline drugs • Act on the bronchial muscles to relieve air way obstruction, increase coronary blood flow and stimulate respiration

3. Theophylline • Natural component in tea that finds pharmaceutical use as a bronchodilator, vasodilator, and a smooth muscle relaxant

4. Tea • From tip leaves of Camellia sinensis • Shrub or small tree native to Tibet, India, China, and Burma. • Still largely grown in this region of the world • Caffeine, theophylline, tannins and theol contribute to flavors and stimulating properties

5. Botanical print of tea plant, Camellia sinensis

6. Workers at tea plantation in the Darjeeling region of India

8. Value of tea • Stimulating effects of tea due to caffeine and theophylline present • Although there is some concern about caffeine intake, people who drink large amounts of green tea have low rates of cancer • Animal studies have shown that rates of breast and prostate cancer reduced by consumption of green tea - attributed to polyphenols in green tea

9. Theophylline • When caffeine metabolized in body, a small amount is actually converted to theophylline • Theophylline used to treat asthma since 1930s by directly relaxing the smooth muscles of the bronchial airways - thereby opening constricted airways • This bronchodilating action helps relieve wheezing, coughing, etc

10. Theophylline • Purine alkaloid • Also called a methyl xanthine alkaloid • Originally extracted from tea • Now chemically synthesized

11. Theophylline • Popular asthma drug for many years • One of first long term bronchodilators • Several trade names and is available in a variety of forms: Theo-Dur, Slo-Bid, Aminophylline are a few of the commonly known medications

12. Side Effects • Theophylline can become toxic • Difference between a therapeutic level and a toxic level is narrow • Side Effects include tachycardia, palpitations, nausea, GI upset, headache, insomnia, arrhythmias, convulsions, urticaria, erythema, dermatitis • Theophylline must also be used with caution in patients with cardiovascular disease, hypertension, or hepatic or renal insufficiency

13. History of theophylline use • Became standard treatment in 1930s • Use declined substantially since 1980s upon realization of the importance of the inflammatory component of asthma • Use of a Beta-2 agonist coupled with steroids became standard management tools • Also concerns about side effects • Theophylline removed from OTC oral medications - inhaled still allowed in 1995

14. Treatment options • Anti-inflammatory effects of inhaled steroids became preferred treatment • For many patients these reduced need for other drugs • However long-term effects of inhaled steroids still unknown • Recent studies show that when used with inhaled steroids, theophylline improves lung function - not just brochodilation

15. Theophylline back in picture?? • Study involved patients with persistent cough, wheeze, or breathlessness despite daily use of inhaled steroids • Patients who received theophylline improved peak flow rates and other measures of lung function • Results showed that therapy combining low dose theophylline with low-dose inhaled steroids is as effective as using high dose steroids alone and avoided side effects

16. How theophylline works • Dilation and relaxation of constricted airways • Increased contraction strength of the diaphragm • Increased beat frequency of the respiratory cilia • Central Nervous System stimulation • Diuretic effects

17. Dilation and relaxation of constricted airways • Main reason for using theophylline • By relaxing the airway muscles, airways enlarge • In asthma, breathing becomes easier • In conditions where fluid or other material has accumulated in airways, dilation of the airways can suppress coughing

18. More on dilation and relaxation • Smooth muscles surround the small airways and, when constricted, narrow airways • Theophylline inhibits cAMP phosphodiesterase, which causes the breakdown of cyclic AMP • Cyclic AMP causes smooth muscle relaxation • By inhibiting cAMP phosphodiesterase, there's more cyclic AMP around to relax smooth muscles

19. Increased contraction strength of the diaphragm • The diaphragm forms the muscular floor of the chest cavity and its contractions correspond to the strength of breathing motions • When breathing becomes difficult, this muscle works harder against the resistance created by disease • Theophylline can strengthen the diaphragm

20. Increased beat frequency of the respiratory cilia • Cells secrete a layer of mucus which captures debris we have inhaled and move debris formed by disease lower down in the lungs • Mucus is moved to throat by cilia on epithelial cells lining respiratory tract - cilia move the mucus and its trapped debris • Once the mucus reaches the throat it is either coughed up or swallowed • Theophylline helps cilia to beat faster and thereby more rapidly clear respiratory debris

21. Central Nervous System stimulation • Stimulating effects of theophylline similar to caffeine, a closely related cmpd • While this can considered be a negative side effect, it can be helpful in infants who suffer from sleep apnea

22. Diuretic • Increased urinary output that may be a problem for some individuals - however the effect is usually mild • May help dry excessive respiratory secretions thus help suppress coughing