Plants Used for Respiratory Problems - II Theophylline

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

Theophylline Alkaloid in tea used as a bronchodilator, vasodilator, and a smooth muscle relaxant

Botanical print of tea plant, Camellia sinensis

Workers at tea plantation in the Darjeeling region of India

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

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

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

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

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

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

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

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