Plants Used for Respiratory Problems - II

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Plants Used for Respiratory Problems - II

• Theophylline

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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

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Theophylline

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

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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

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Botanical print of tea plant, Camellia sinensis
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Workers at tea plantation in the Darjeeling
region of India
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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

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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

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Theophylline

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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