Plants Used for Respiratory Problems

1. Plants Used for Respiratory Problems

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 • edema of bronchial walls • retention of viscid bronchial secretions

5. Normal Function of Airway

6. Asthmatic lungs

7. Asthma Increase • 15 to 18 million people in US suffer from asthma including 5 million children • $5 billion in medical costs each year • Since 1980, asthma reports have increased 75% - up 160% in children • Exact reason not certain - possibly better diagnosis, possibly increased exposure to indoor allergens - possibly lifestyle changes

8. Asthma Treatment • Many treatment options • Bronchodilators • Anti-inflammatories • Allergy shots (desensitization)

9. 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

10. 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 of the bronchial muscles to relieve obstruction, increase coronary blood flow and stimulate respiration

11. A very short list of plant extracts • Ephedrine • Theophylline

12. Ephedra Ephedrine and Pseudoephedrine

13. Ephedra spp. Gymnosperm in Division Gnetophyta - very small group of gymnosperms - 3 genera Lots of botanical interest Small shrub common in arid and desert areas - widely distributed in these habitats Reduced scale-like leaves Stem green and photosynthetic Ephedra sinica well known as source of drug ephedrine

16. Medicinal Use of Ephedra • Long history of use as a medicinal plant especially as a decongestant for asthma, bronchitis, and other respiratory conditions • In China, Ephedra sinica – called Ma Huang has been used for thousands of years • Also well known as a stimulant

17. Stimulant use well known • Its use as stimulant is because it is similar in action to adrenaline and amphetamines • increases heart rate and blood pressure • found in many OTC herbal drugs • abuse as a “legal” street drug

18. Alkaloids in Ephedra • Ephedrine and pseudoephedrine • Ephedrine used in prescription drugs since the 1920s • Also used in OTC drugs • Very effective decongestants – relaxes bronchial muscles and opens airways • Also CNS stimulant that increases heart rate and blood pressure and blood flow to brain • Stimulating properties of pseudoephedrine not as great and preferred today

19. Ephedrine

20. Pseudoephedrine

21. Mode of Action • Ephedrine and pseudoephedrine can cross the blood/brain barrier • Mimic activity of the sympathetic nervous system by interacting with various neurotransmitters • Specifically, ephedrine enhances the release of the hormone/neurotransmitter norepinephrine and stimulates alpha and beta–adrenergic receptors

22. More mode of action • Beta-2 receptors in the lungs are stimulated to open the airways - this is responsible for its effectiveness as a bronchodilator • Other types of receptors also stimulated: • Beta-1 receptors in the heart increase heart rate and force of contraction • Alpha-1 receptors increase blood pressure and decrease circulation to the renal system and other parts of the body

23. 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

24. 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

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

26. Other beta-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 beta-2 receptors • Epinephrine still used in emergency treatment of asthma – Epi-pens

27. 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 • Since ephedrine chemically similar to epinephrine, it works like a powerful cardiac stimulant and may cause cardiac arrest in infants and heart patients

28. 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

29. Ephedrine sources • Chinese species Ephedra sinica original source of the alkaloid ephedrine • Today ephedrine is synthesized in lab • New synthetic drugs based on ephedrine ring structure are now marketed as effective and safer bronchodilators

30. Pseudoephedrine • Compared to ephedrine, it causes fewer heart symptoms such as palpitations, but is equally effective as a bronchodilator • Today also synthesized in lab • It is used in many over-the-counter drugs • Ephedra sinica and other species are also marketed under the name of "ma-huang," a popular herbal stimulant and decongestant

31. Many OTC products

32. Abuse of Ephedrine • Stimulating effects of ephedrine similar to to amphetamines • This had led to street abuse of Ephedra products • Described as “herbal ecstasy” • Serious side effects can occur – irregular heart beats, dizziness, heart attacks, strokes, seizures • Hundreds have suffered serious effects • Several states have passed laws regulating the sale – as a controlled substance • FDA has proposed limits on amounts in herbals • Ephedrine can also be chemically converted into methamphetamine or "crank“