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
Alkaloid in tea used 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. Theophylline Purine alkaloid Also called a methyl xanthine alkaloid
Originally extracted from tea
Now chemically synthesized

8. 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

9. 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

10. 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

11. Theophylline mode of action
Dilate and relax constricted airways
Increased contraction strength of the diaphragm
Increased beat frequency of the respiratory cilia
Side effects
Central nervous system stimulation
Diuretic effects

12. More on dilation and relaxation of airways
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

13. Increased contraction strength of the diaphragm
Theophylline can strengthen the diaphragm
Increases the force of contraction of diaphragm muscles which draws more air into the lungs
This is believed due to enhanced calcium uptake through an adenosine mediated channel

14. 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