1. Plants Used for Respiratory Problems - I

2. Respiratory Problems Various conditions can interfere with the gas exchange in the lungs Infectious disease Chronic diseases Asthma Emphysema

3. Asthma Chronic breathing disorder Characterized by inflammation of the airways, bronchial constriction, excessive mucous secretion - results in wheezing, coughing, and choking Responsible for 5,000 deaths/yr in the US Attacks triggered by exposure to allergens and also infections, stress, exercise

4. Airway constriction Narrowing of airways due to contraction of the smooth muscles Inflammation/edema of bronchial walls retention of viscid bronchial secretions

5. Normal Function of Airway

6. Asthmatic lungs

7. Asthma Increase Close to 21 million people in US suffer from asthma including 6.1 million children (based on 2002 statistics) Over $14 billion in medical costs each year – including direct medical costs and lost productivity Since 1980, asthma reports have increased 75% - up 160% in children Increase especially seen in inner city – survey in south Bronx indicated that 28% of children had asthma symptoms Exact reason not certain - possibly better diagnosis, possibly increased exposure to indoor allergens, outdoor pollutants, possibly lifestyle changes, lots of theories!

10. Current asthma and asthma attack prevalence, 2002 13.1% 9.9% 9.5% 7.2% 3.6% 7.2%

12. Asthma Treatment Many treatment options Bronchodilators Anti-inflammatory drugs Allergy shots (desensitization)

13. Bronchodilators Help to stop asthma attacks after they've started Can help prevent expected attacks, as from exercise Relax smooth muscles of bronchioles - this opens bronchioles and makes breathing easier

14. Bronchodilators What do they do 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 obstruction, increase coronary blood flow and stimulate respiration

15. A very short list of plant extracts Ephedrine Theophylline

16. Ephedra species Ephedrine and Pseudoephedrine

17. Ephedra : A gymnosperm in the Division Gnetophyta

19. Use of Ephedra Long history of use In China, Ephedra sinica – called Ma Huang Alkaloids Ephedrine, Pseudoephedrine Others

20. Ephedrine and Pseudoephedrine are stereo-isomers EphedrinePseudoephedrine

21. Mode of action Mimic adrenal hormones – epinephrine and norepinephrine Stimulates  and  adrenergic receptors  -2 receptors in the lungs are stimulated to open the airways - this is responsible for its effectiveness as a bronchodilator Other receptors also stimulated :  -1 receptors in the heart increase heart rate and force of contraction  -1 receptors increase blood pressure and decrease circulation to the renal system and other parts of the body

22. Adrenal Hormones Increased rate and force of contraction of the heart muscle: predominantly an effect of epinephrine acting through beta receptors Constriction of blood vessels: norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and blood pressure Dilation of bronchioles: assists in pulmonary ventilation

23. More on adrenal hormones Stimulation of lipolysis in fat cells: provides fatty acids for energy production in many tissues and aids in conservation of dwindling reserves of blood glucose. Increased metabolic rate: oxygen consumption and heat production increase in response to epinephrine Hormones also promote breakdown of glycogen in skeletal muscle to provide glucose for energy production

24. Epinephrine and Norepinephrine Synthesized in the body from a.a. Tyrosine

25. New  -2 agonists Epinephrine (adrenaline) was once a conventional treatment for asthma similar to ephedrine but much more active and short-acting Epinephrine was replaced by current asthma medications which are able to act more selectively on  -2 receptors Epinephrine still used in emergency treatment of asthma – Epi-pens

26. Common side effects of ephedrine Headache, irritability, restlessness of muscles, nausea, sleeplessness, increased heart rate, urinary disturbances and vomiting Higher dosages may result in drastic increases in blood pressure and cardiac rhythm disorders, heart palpitations Since ephedrine chemically similar to epinephrine, it works like a powerful cardiac stimulant and may cause cardiac arrest in infants and heart patients

27. Ephedrine contra-indicated Non-specific stimulation of adrenergic receptors means that Ephedra products should not be used in people with anxiety and restlessness high blood pressure glaucoma impaired circulation of the cerebrum prostate adenoma

28. Ephedrine and pseudoephedrine uses Originally Ephedra sinica Synthesized in lab today New synthetics available Pseudoephedrine preferred Many OTC Herbal supplements – Ma Huang Ephedrine abuse

29. Many OTC products