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. Botanical print of tea plant, Camellia sinensis

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

7. 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

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

9. Theophylline use in asthma • Many trade names: Theo-Dur, Slo-Bid, Uniphyl, Theo 24, Aminophylline • Side Effects: 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

10. 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 b-2 agonist coupled with inhaled steroids became standard management tools • Also concerns about side effects • Theophylline removed from OTC oral medications – still available by prescription

11. Theophylline back in picture?? • Recent 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

12. 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

13. 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

14. More on dilation and relaxation • Smooth muscles surround the small airways and, when constricted, narrow airways • Theophylline inhibits cAMP phosphodiesterase (PDE-III), 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

15. Increased contraction strength of the diaphragm • Theophylline can strengthen the diaphragm • Increases the force of contraction of diaphragm muscles • This is believed due to enhanced calcium uptake through an adenosine mediated channel

16. 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