Phytotherapy - Introduction PDF

Phytotherapy Dr. Nour Aboalhaija Faculty of Pharmacy/ Al-Zaytoonah University 0 1 2 2 3 4 5 6 0 1 2 2 3 4 5 6 Introduction • Conventional medicine is traditional medicine that the majority of us are familiar with — local doctors, clinics, hospitals, pharmacies. It’s the kind of medicine th...

Phytotherapy Dr. Nour Aboalhaija Faculty of Pharmacy/ Al-Zaytoonah University 0 1 2 2 3 4 5 6 0 1 2 2 3 4 5 6 Introduction • Conventional medicine is traditional medicine that the majority of us are familiar with — local doctors, clinics, hospitals, pharmacies. It’s the kind of medicine the average physician practices. • Alternative medicine includes a philosophy and practice that is inclusive of a variety of world cultures. • Plant extracts are now rarely used by physicians or in hospitals, although herbal remedies are popular with the public and improvements in their formulation have resulted in a new generation of phytomedicines that are more potent than before and also chemically standardized. Al-Zaytoonah University Dr. Nour Aboalhaija 4 Introduction • There is, however, a recovery of interest in the older Oriental systems; this is due partly to dissatisfaction with conventional treatments and partly to the constantly growing interest in all things natural, environmentally friendly and biodegradable. • Whether or not pharmacists, doctors and other healthcare professionals accept the validity of these older medical systems, it is necessary for them to know about their basic principles for two main reasons. First, to be in a position to advise patients who may wish to consult an alternative practitioner and, second, because traditional use is a common starting point in the ongoing search for new drugs. Al-Zaytoonah University Dr. Nour Aboalhaija 5 Conventional Medicine Complementary and Alternative Medicine (CAM) Al-Zaytoonah University Dr. Nour Aboalhaija 6 Introduction Selected examples of CAM Herbal medicine Aromatherapy Homeopathy Al-Zaytoonah University Dr. Nour Aboalhaija 7 Introduction TYPES OF DRUGS DERIVED FROM PLANTS (I) NATURAL PRODUCTS OR COMPOUNDS ISOLATED FROM NATURE These are pure chemical entities, often used in the form of licensed medicines. They are sometimes produced synthetically and referred to as ‘nature identical’ (if that is the case), but were originally discovered from plant drugs. Examples include: o morphine, from opium poppy (Papaver somniferum), used as an analgesic o digoxin and other digitalis glycosides, from foxglove (Digitalis spp.), used to treat heart failure Al-Zaytoonah University Dr. Nour Aboalhaija 8 Introduction (II) NUTRACEUTICALS OR ‘FUNCTIONAL FOODS’ Many foods are known to have beneficial effects on health. Examples include: o garlic, ginger, turmeric and many other herbs and spices o anthocyanin- or flavonoid-containing plants such as bilberries, cocoa and red wine o carotenoid-containing plants such as tomatoes, carrots and many other vegetables. Al-Zaytoonah University Dr. Nour Aboalhaija 9 Introduction TYPES OF DRUGS DERIVED FROM PLANTS III) HERBAL DRUGS DERIVED FROM SPECIFIC PARTS OF A MEDICINAL PLANT Botanical drugs which form the basis for herbal remedies or phytomedicines include, for example: o the herb of St John’s wort (Hypericum perforatum), used in the treatment of mild to moderate depression o the leaves of Ginkgo biloba, used for cognitive deficiencies (often in the elderly), including impairment of memory and affective symptoms such as anxiety o the flower heads of chamomile (Chamomilla recutita), used for mild gastrointestinal complaints and as an antiinflammatory agent Al-Zaytoonah University Dr. Nour Aboalhaija 10 Introduction TYPES OF DRUGS DERIVED FROM PLANTS III) HERBAL DRUGS DERIVED FROM SPECIFIC PARTS OF A MEDICINAL PLANT From the perspective of pharmacognosy and rational phytotherapy, such products lie alongside, conventional pharmaceutical medicines. Herbal medicines are often considered to be part of complementary and alternative medicine (CAM), and the use of herbal medicinal products (HMPs) and of CAM has increased across the developed world. Al-Zaytoonah University Dr. Nour Aboalhaija 11 Introduction Herbal Medicine (Phytomedicine) It is a type of crude medicine that uses plants or their products for treatment of diseases. It includes four branches: Phytopharmacy. Phytochemistry. Phytopharmacology. phytotherapy. Al-Zaytoonah University Dr. Nour Aboalhaija 12 Introduction Phytopharmacy It is a branch of herbal medicine deals with the preparation of natural drugs either in natural form (medicinal teas), or in pharmaceutical preparations (tinctures and extracts). It includes pharmacognosy that concentrate in the identification of natural drugs either in entire or in powdered forms and the detection of their adulteration. Al-Zaytoonah University Dr. Nour Aboalhaija 13 Introduction Phytochemistry It is a branch of herbal medicine that deals with the study of chemical constituents of the plants such as alkaloids ,glycosides, essential oils. It explains their distribution , isolation chemical reaction and biosynthesis. Al-Zaytoonah University Dr. Nour Aboalhaija 14 Introduction Phytopharmacology It is a branch of herbal medicine that is concerned with testing natural drugs which have multiple effects on animals and humans. Phytotherapy It is a branch of herbal medicine that describes the potential and limitations of herbal drugs in treatment of diseases. Al-Zaytoonah University Dr. Nour Aboalhaija 15 Introduction Advantages of herbal medicines 1. Numbers of herbal preparations interfering with the safety and efficacy of synthetic drugs is small. 2. Herbal medicines usually have a wide therapeutic range (the gap between therapeutic and toxic doses is very large). Subsequently, herbal medicines provide a high level of treatment safety. Al-Zaytoonah University Dr. Nour Aboalhaija 16 Introduction Advantages of herbal medicines 3. Herbal medicines are very cheap in comparison to the conventional form of medication. 4. When given a choice, patients tend to accept them more readily than synthetic drugs, thereby increasing compliance. 5. Herbal medicines can be found very easily in rural areas 6. Offer long lasting benefits in terms of overall wellness. Al-Zaytoonah University Dr. Nour Aboalhaija 17 Introduction Disadvantages of herbal medicines 1. Herbal medicines are taken without prescription which means that in some cases, individual might be undergoing a trial and error process with their medication. 2. The curing period is usually longer in comparison to conventional medication. Al-Zaytoonah University Dr. Nour Aboalhaija 18 Introduction Disadvantages of herbal medicines 3. Herbal medicines are known to be ineffective against serious ailments as heart attack. 4. Herbal medicines can cause allergic reactions in some cases. 5. The improper long-term use of certain herbal preparations can lead to severe side effects. Al-Zaytoonah University Dr. Nour Aboalhaija 19 Introduction Herbal Regulations  The use of medicinal plants is the most common form of CAM worldwide.  Regulation of herbal medicines is a key means of ensuring safety, efficacy and quality of herbal medicinal products.  During the last years, many countries have established, or initiated the process of establishing national regulations regarding herbal medicines. Al-Zaytoonah University Dr. Nour Aboalhaija 20 Introduction Herbal Regulations The regulation of herbal medicines is complex, varies greatly and is constantly changing. These diverse regulatory frameworks form an essential basis for the activities of all healthcare professionals and for research on such products. For example, in the UK, until recently Ginkgo biloba was considered a food and now is, as in other European countries, regulated as a HMP; it is a HMP herbal medical product in Germany and a food supplement in the USA. Al-Zaytoonah University Dr. Nour Aboalhaija 21 Introduction  Herbal Regulations UNITED STATES OF AMERICA (USA) In the USA, herbal medicines are generally regulated as ‘dietary supplements’. The US Food and Drug Administration (FDA, www.fda.gov/Food/ DietarySupplements/) is in charge of these comparatively loose regulations. - Prior to marketing, dietary supplements do not have to be assessed for safety and effectiveness. Limited therapeutic claims may be made, e.g. that a dietary supplement addresses a nutrient deficiency, supports health, or is linked to a particular body function (e.g. immunity). Al-Zaytoonah University Dr. Nour Aboalhaija 22 Introduction  Herbal Regulations UNITED STATES OF AMERICA (USA) However, this requires supportive prior research. Such a claim must be followed by the words ‘This statement has not been evaluated by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.’ Al-Zaytoonah University Dr. Nour Aboalhaija 23 Introduction  Herbal Regulations CANADA In Canada herbal medicines are classified as ‘natural health products’ which require a product licence before they can be marketed. The relevant agency is ‘Health Canada’. Al-Zaytoonah University Dr. Nour Aboalhaija 24 Introduction  Examples on Regulatory Agencies  European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or European Medicines Evaluation Agency (EMEA) Al-Zaytoonah University Dr. Nour Aboalhaija 25 Introduction Monographs A publication that specifies - for a drug (or class of related drugs)- the kinds and amounts of ingredients it may contain, the conditions and limitations for which it may be offered, directions for use, warnings, interactions with other drugs and other information that its labeling must contain. Al-Zaytoonah University Dr. Nour Aboalhaija 26 27 Al-Zaytoonah University Dr. Nour Aboalhaija 28 Al-Zaytoonah University Dr. Nour Aboalhaija 29 Al-Zaytoonah University Dr. Nour Aboalhaija 30 Introduction Purpose and Content of the Monograph Provide scientific information on the safety, efficacy, and quality control/quality assurance of widely used medicinal plants, in order to facilitate their appropriate use in Member States. Provide models to assist Member States in developing their own monographs or formularies for these or other herbal medicines. Facilitate information exchange among Member States. Al-Zaytoonah University Dr. Nour Aboalhaija 31 Introduction Evidence Based Medicine Evidence Based Medicine : The practice of medicine based on medical efficacy proven by clinical trials. Al-Zaytoonah University Dr. Nour Aboalhaija 32 Introduction Clinical Trials since the late 90s, there has been a significant increase in the publication of randomized clinical trials on herbs. A randomized controlled trial (RCT): is a form of clinical trial - most used in testing the safety and efficacy of healthcare services. Al-Zaytoonah University Dr. Nour Aboalhaija 33 Introduction Clinical Trials The key distinguishing feature of the usual RCT is that study subjects are randomly allocated to receive one or other of the alternative treatments under study. After randomization, the two (or more) groups of subjects are followed up in exactly the same way, and the only differences should be those intrinsic to the treatments being compared. The most important advantage of proper randomization is that it minimizes allocation bias. Al-Zaytoonah University Dr. Nour Aboalhaija 34 Introduction Al-Zaytoonah University Dr. Nour Aboalhaija 35 Introduction Quality control: is the term that involves in processes involved in maintaining the quality and validity of manufactured product. Quality control is based on three important pharmacopeial definitions: 1. Identity 2. Purity 3. Assay /content Al-Zaytoonah University Dr. Nour Aboalhaija 36 Introduction Drug Standardization: is the “confirmation of its identity and determination of its quality and purity and detection of nature of adulterants by various parameters like morphological, microscopical, physical, chemical and biological observations.” Follows Good Manufacturing Practice (GMP) Al-Zaytoonah University Dr. Nour Aboalhaija 37 Introduction Parameters Involved in the Standardization of Crude Drugs: 1. Organoleptic Parameters 2. Botanical Parameters • Macroscopic parameters • Microscopic parameters 3. 4. 5. 6. Physical Parameters Chemical Parameters Biological Parameters Toxicological Parameters Al-Zaytoonah University Dr. Nour Aboalhaija 38 Standardization of Herbal drugs •Shape •External •Marking Macroscopic Microscopic STANDARDISATION OF HERBAL DRUGS Microbial Parameters • Total viable aerobic count • Determination of pathogens Pharmacological Parameters • • • • Bitterness value Hemolytic activity Foaming index Swelling index Toxicological Parameters • Determination of pesticide residues • Determination of heavy metals • Radioactive contamination Rawat A.K.S., Tewari S.K. (2015) Quality Assurance of Medicinal and Aromatic Plants- Good Agricultural and Collection Practices (GAP & GCP). In: Máthé 39 Á. (eds) Medicinal and Aromatic Plants of the World. Medicinal and Aromatic Plants of the World, vol 1. Springer, Dordrecht Introduction Markers Marker is a pure, single isolated secondary metabolite. Markers are chemically defined constituents or groups of constituents of a herbal substance, a herbal preparation or a herbal medicinal product which are of interest for control purpose independent of whether they have any therapeutic activity. Markers serve to calculate the quantity of herbal substance(s) or herbal preparation(s) in the Herbal Medicinal Product. Al-Zaytoonah University Dr. Nour Aboalhaija 40 Introduction Markers Active marker are constituents or group of constituents which are generally accepted to contribute to the therapeutic activity. Analytical marker are constituents or groups of constituents that serve for analytical purpose. Al-Zaytoonah University Dr. Nour Aboalhaija 41 Introduction Herb-Drug interactions • Herb-drug interactions appear to be much less frequent and less serious than drug-drug interactions. • This primarily reflects a weaker pharmacologic profile for herbs compared to their potent pharmaceutical counterparts, but most likely also reflects: under-recognition, under-reporting, and less research. • As with other drugs, the risk of unexpected effects may be influenced by a user’s age, gender, genetics, nutrition status, and concurrent disease states and treatments. Al-Zaytoonah University Dr. Nour Aboalhaija 42 Introduction Herb-Drug interactions • Much of the known information on herb-drug interactions is based on case reports of varying quality. • Inconsistencies of product formulations, combinations of herbs, and poor-quality control (leading to adulteration or contamination) also limit the conclusions and generalizations that can be derived. • Nevertheless, case reports can caution of possible interactions (especially when multiple reports are published that help to confirm an association) that worth further study. Al-Zaytoonah University Dr. Nour Aboalhaija 43 Introduction Herb-Drug interactions • Herbs and drugs usually interact in two general ways: pharmacokinetically and pharmacodynamically. • Pharmacokinetic interactions result in alterations of a drug's absorption, distribution, metabolism, or elimination—quantitatively increasing or decreasing the amount that becomes effective in the body. • Pharmacodynamic interactions alter the way the herb or drug affects a target tissue, organ system, receptor, etc. qualitatively, usually enhancing or antagonizing the drug's properties. Al-Zaytoonah University Dr. Nour Aboalhaija 44 Introduction Herb-Drug interactions • Absorption • Interactions affecting absorption result in a reduction/increase of the absorption of the drug. • Changes in intestinal pH • Complexing mechanisms and drugs affecting intestinal motility will affect absorption Al-Zaytoonah University Dr. Nour Aboalhaija 45 Introduction Herb-Drug interactions Herbs that may affect absorption of other drugs 1) Tannin-containing herbs  Tannins are broadly distributed throughout the plant kingdom. They can complex with proteins, resulting in an astringent effect on skin or mucous membranes.  Herbs with high tannin content can precipitate alkaloid drugs and metal ions in vitro.  Examples: eucalyptus, horse chestnut, pomegranate, raspberry, rhubarb, tea (black, green, oolong [a traditional Chinese tea] ) and uva ursi. Al-Zaytoonah University Dr. Nour Aboalhaija 46 Introduction Herb-Drug interactions Herbs that may affect absorption of other drugs 2) Cathartic herbs Most stimulant laxative herbs contain anthranoids, particularly anthraquinone glycosides, which stimulate colonic peristalsis, and thus may reduce absorption of other drugs by reducing gut transit time. Laxative abuse can lead to hypokalemia and other electrolyte disturbances that can result in interactions with drugs such as digoxin. Examples: Aloe vera juice, cascara, castor seed oil, frangula, rhubarb, senna. Al-Zaytoonah University Dr. Nour Aboalhaija 47 Introduction Herb-Drug interactions Herbs that may affect absorption of other drugs 3) High fiber (mucilage) herbs Herbs that contain water-soluble hydrocolloidal fiber (forming a mucilage or gel) can theoretically impair absorption of many different drugs. These herbs are often utilized as bulk-forming laxatives. A few interactions have been documented in humans.  Examples: acacia ( gum arabic). Al-Zaytoonah University Dr. Nour Aboalhaija 48 Introduction Herb-Drug interactions Distribution A drug with high plasma protein binding (e.g. warfarin, carbamazepine) that has a small volume of distribution may be displaced by a herb competing for the same binding sites. Drug displacement from protein-bound forms, by concurrent drug administration, causes an increase in serum drug levels and which may lead to an increase in therapeutic effect. Al-Zaytoonah University Dr. Nour Aboalhaija 49 Introduction Herb-Drug interactions Metabolism 1- Enzyme Induction A decrease in the amount of drug could occur by stimulating the production and activity of enzymes that degrade the drug and prepare it for elimination from the body. Such is the case with St. John’s Wort which induces the cytochrome P450 enzymes which are responsible for the metabolism of several drugs. This is a common mechanism and applies to the way in which St. John’s Wort may reduce the efficacy of the oral contraceptive pill or blood levels of warfarin, digoxin, theophylline, carbamazepine. Al-Zaytoonah University Dr. Nour Aboalhaija 50 Introduction Herb-Drug interactions Metabolism 2- Enzyme Inhibition The opposite may also occur, in which the herb inhibits the production of the enzyme required to break down the drug, hence increasing the drug levels. Unlike enzyme induction, which may take several days or weeks to fully develop, enzyme inhibition can occur within 2-3 days resulting in a rapid development of toxicity.. Licorice decreases the metabolism of corticosteroids, leading to adverse and toxic effects from the build-up of corticosteroids. Evidence obtained in vitro suggests that Echinacea and chamomile may inhibit the cytochrome P450. Concurrent use with drugs like alprazolam, simvastatin and calcium-channel blockers could potentially increase serum drug levels and adverse effects. Al-Zaytoonah University Dr. Nour Aboalhaija 51 Introduction Herb-Drug interactions Excretion Changes in excretion may also affect serum drug levels.. Herbal diuretics are quite weak and unlikely to cause large problems. However, chronic ingestion of liquorice may result in hypokalemia and water retention and accordingly may interfere with various medications including antihypertensive and antiarrhythmic agents. Al-Zaytoonah University Dr. Nour Aboalhaija 52 Introduction Herb-Drug interactions Excretion Diuretic herbs This property is primarily based on traditional usage or animal experiments. Diuretic herbs may potentially deplete potassium, while "aquaretic" herbs are said to enhance water elimination without depleting electrolytes. Examples: buchu, caffeine-containing herbs (cocoa bean, coffee seed, cola seed, tea - black, green, oolong), celery and parsley. Al-Zaytoonah University Dr. Nour Aboalhaija 53 Introduction Herb-Drug interactions Pharmacodynamic Interactions • Pharmacodynamic interactions can affect drug actions qualitatively, usually enhancing or antagonizing the drug’s effect, but they may also have indirect effects (e.g., the herb that increases potassium excretion can increase the risk of digoxin toxicity). • Outcomes will also vary considerably based on the herb's route of administration, the dose or concentration, and the patient's individual tolerance. Al-Zaytoonah University Dr. Nour Aboalhaija 54 Introduction Herb-Drug interactions Pharmacodynamic Interactions Additive interactions • Herb might produce the same kind of effect as the drug and give an increase in the drug effect (without increasing the amount of the drug). Therefore herbal sedatives, anticoagulants, antihypertensives and others may possibly increase the effect of a concurrent conventional drug taken for the same purpose. For example, the hypnotic activity of benzodiazepines is increased by valerian. Al-Zaytoonah University Dr. Nour Aboalhaija 55 Introduction Herb-Drug interactions Pharmacodynamic Interactions Antagonistic interactions  Herb might produce an effect that is contrary to the effect desired for the drug, thereby reducing the drug effect. Hypertensive herbs Herbs known to contain sympathomimetics (ephedra, yohimbe) especially in large doses. caffeine-containing herbs (cola nut, coffee, tea), often used in combination in many herbal weight-loss products, they have cardiovascular effects that may antagonize the effects of antihypertensive medications Al-Zaytoonah University Dr. Nour Aboalhaija 56 Introduction Herb-Drug interactions Immunostimulant herbs  These herbs having tonic or immune benefits or have been reported to cause nonspecific immune stimulation in laboratory tests. .  Stimulation could theoretically activate autoimmune processes or interfere with immune supressive drug treatment. However, there are no documented clinical reports of adverse interactions .  Examples: Echinacea and Calendula. Al-Zaytoonah University Dr. Nour Aboalhaija 57 Introduction Herb-Drug interactions Herbs That May interfere With Coagulation a) Coumarin-containing plants  They are often considered to enhance the effects of anticoagulant or antiplatelet drugs.  However, coumarin and many coumarin derivatives (a large class of over 1300 natural chemicals) have been confused by herbalists and health professionals with the semisynthetic drug Coumadin or warfarin. Al-Zaytoonah University Dr. Nour Aboalhaija 58 Introduction Herb-Drug interactions Herbs That May interfere With Coagulation a) Coumarin-containing plants  One particular mold converts a specific coumarin compound in sweet clover (4-hydroxycoumarin) to the anticoagulant bishydroxy-coumarin (dicoumarol); this is the cause of bleeding in cattle grazing on moldy sweet clover.  Anticoagulant effects occurring with the numerous other coumarin-containing plants are unlikely. Al-Zaytoonah University Dr. Nour Aboalhaija 59 Introduction Herb-Drug interactions Herbs That May interfere With Coagulation b) Vitamin K-rich plants  These plants, mostly green leafy vegetables, may diminish the anticoagulant effects of warfarin, especially when consumed habitually.  Examples: cruciferous vegetables (broccoli, cabbage), lettuce, spinach. Al-Zaytoonah University Dr. Nour Aboalhaija 60 Introduction Herb-Drug interactions Herbs That May interfere With Coagulation c) Antiplatelet aggregation herbs Many herbs have been reported to inhibit platelet aggregation in vitro. Health professionals may wish to check bleeding times for patients at high risk of bleeding (e.g., taking warfarin, preparation for surgery). Examples: asian ginseng, clove, garlic, ginger. Al-Zaytoonah University Dr. Nour Aboalhaija 61 Introduction From plant to medicine:  Modern phytotherapeutic preparations are usually prepared from plant extracts. And in contrast with synthetics, it is typical that a product contains a combination of several extracts.  For example in the case of functional gastrointestinal problems, it is wise to apply plants with different mechanisms of actions to provide relief for the different components of the syndrome.  However, there is no general basis for the common place saying that combination products are useful since each of the components strengthens the effect of the others. The oppose may occur. Al-Zaytoonah University Dr. Nour Aboalhaija 62 Introduction From plant to medicine: The use of herbal extracts in phytotherapeutics has several advantages. 1. Extraction ensures that enzymatic processes do not alter the composition of the product, and the microbiological stability of extracts is greater than that of dry plant materials. 2. If concentrated extracts are prepared it is possible to administer quite large doses of plant material in a convenient way (e.g. 1 capsule instead of 50 g of dry leaf). The measure of concentration is characterized by the drug-extract ratio (DER). The DER indicates how many grams of plant material are used to produce 1 g of extract. Al-Zaytoonah University Dr. Nour Aboalhaija 63 Introduction From plant to medicine: For example, if the DER is 5:1, 1 g of extract is prepared from 5 g of plant material (the measure of “concentration” is 5-fold). In certain cases, the DER is given as a range, e.g. 5-10:1. The reason for this is that the compositions of herbal raw materials harvested in different places and at different times may vary greatly and the amount of extract that can be gained from a specific amount may vary accordingly. Depending on the extent of evaporation, the native liquid extracts may even result in semisolid or solid (dry) extracts. Al-Zaytoonah University Dr. Nour Aboalhaija 64 Introduction From plant to medicine: The extracting solvent has important effect on the quality (and quantitative composition) of the extract. If the active components of a plant are lipophilic, apolar (nonpolar, lipophilic) solvents should be preferred. If the active component (the secondary metabolite of a plant that is responsible for the pharmacologic effect) is known, it is more important to keep its level constant in the final product than to adhere to a very specific DER. Al-Zaytoonah University Dr. Nour Aboalhaija 65 Introduction Herbal Formulations 1- Tinctures: They are alcoholic extracts of herbs usually obtained by combining pure ethanol with the herb. A completed tincture has an ethanol percentage of at least 25% (sometimes up to 90%). Advantages: This method can concentrate the medicine, making it more potent, long lasting. Al-Zaytoonah University Dr. Nour Aboalhaija 66 Introduction Herbal Formulations 1- Tinctures: Disadvantages: Can't be used in case of alcohol intolerance, they can be expensive especially if needed over a long period of time, and strongly flavored. Storage : Should not be stored for more than one year owing to the potential instability of certain compounds in the extract. Note: Many tinctures should not be used undiluted. Al-Zaytoonah University Dr. Nour Aboalhaija 67 Introduction Herbal Formulations 2- Extracts: Include liquid extracts and dry extracts . Liquid extracts are liquids with a lower ethanol percentage than tinctures. Dry extracts are extracts of plant material which are evaporated into a dry mass. They can then be further refined to a capsule or tablet. Advantages: Very easy to be administered, good adjustment for the dose. Al-Zaytoonah University Dr. Nour Aboalhaija 68 Introduction Herbal Formulations 3- Syrups: are extracts of herbs made with syrup or honey. 65% sugar are mixed with 35% aqueous herbal extract. The whole is then boiled and macerated for three weeks. Advantages: Easy to prepare, easily tolerated, mask unpleasant flavor. Disadvantages: Not all constituents can be extracted by this method. Al-Zaytoonah University Dr. Nour Aboalhaija 69 Introduction Herbal Formulations 4- Herbal teas: They are hot water extracts of herbs, such as chamomile or mint. The concentrations of active principles in medicinal teas are determined by the relative proportion of the herbs to extractant (water), the degree of cutting or grinding of the herb , and the recommended water temperature. Herb teas, such as lobelia, with a strong medicinal action. Best used under the guidance of an experienced health care professional . Many milder teas like ginger, peppermint, and chamomile have some medicinal qualities, but are usually considered safe to use at home with care. Al-Zaytoonah University Dr. Nour Aboalhaija 70 Introduction Herbal Formulations 4- Herbal teas: Preparation: Plant materials are cut coarsely to finely. Advantages: Easy to prepare, inexpensive, easily tolerated. Disadvantages: 1. It is difficult to determine the exact dosage 2. Cutting or powdering of herbs often drastically reduces their shelf life by allowing oxygen to reach and degrade active constituents 3. Do not last long once made 4. Flavor may not be tolerated Al-Zaytoonah University Dr. Nour Aboalhaija 71 Introduction Herbal Formulations 4- Herbal teas: Methods of tea preparations  Infusion: Preparation made by pouring boiling water onto the fresh or dried herbs and allowing them to steep in order to extract their medicinal principles. Suitable for the preparation of delicate or finely chopped herbs (leaves, flowers) with volatile and thermolabile constituents (e. g., essential oils).  Decoction: Prepared by boiling fresh or dried herbs in water for 10 to 60 minutes to extract their medicinal principles. Suitable for the preparation of hard or very hard plant materials (woods, barks, roots) or herbs with sparingly soluble constituents. Al-Zaytoonah University Dr. Nour Aboalhaija 72 Introduction Herbal Formulations 4- Herbal teas: Methods of tea preparations  Maceration (cold extract): Prepared by allowing a tea herb to steep in cold water for several hours to extract its active principles. Suitable for the preparation of mucilage-containing herbs such as flaxseeds whose high concentrations of starches and pectin would cause them to gelatinize if prepared with boiling water. Also used to prevent the extraction of undesirable constituents that dissolve in hot water. Freeze drying or lyophilization: is a water removal process typically used to preserve some materials, to extend shelf life or make the material more convenient for transport. Freeze drying works by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate Al-Zaytoonah University Dr. Nour Aboalhaija 73 Introduction Herbal Formulations 5- Solid Dosage Forms oTablets and capsules are currently preferred by many patients because of the following advantages: - They are convenient and familiar dosage forms. - They do not present problems with taste or alcohol content. Crude herbs can be air-dried, freeze-dried, or ground and used to fill gelatin capsules or compressed into tablets. Al-Zaytoonah University Dr. Nour Aboalhaija 74 Introduction Herbal Formulations 5- Solid Dosage Forms o Tablets and capsules: Disadvantages: 1 - The limited amounts of whole herb that can be incorporated into these solid forms. (To overcome this problem more concentrated extracts are often required. To prepare a solid extract, the herb is first extracted with a solvent, as in preparing a liquid extracts. The resultant liquid is then evaporated by various methods, and a concentrated solid is then incorporated into the tablets or capsules). 2- Heat-sensitive or volatile components can be damaged or lost during processing such as granulation & other processes involving heat. Al-Zaytoonah University Dr. Nour Aboalhaija 75 Introduction Herbal Formulations 5- Solid Dosage Forms o Powders Sometimes the best way to prescribe a herb is as a powder. This particularly applies to mucilage-containing drugs. When giving mucilaginous herbs as powders it is best to advise the patient to mix them quickly with water & to take the mixture without delay before it swells. Al-Zaytoonah University Dr. Nour Aboalhaija 76 Introduction Selected examples of CAM Herbal medicine Homeopathy Aromatherapy Al-Zaytoonah University Dr. Nour Aboalhaija 77 Homeopathy History: Homeopathic medicine is a whole medical system that was developed in Germany more than 200 years ago and has been practiced in the United States since the early 19th century. The term homeopathy comes from the Greek words homeo, meaning similar, and pathos, meaning suffering or disease. Al-Zaytoonah University Dr. Nour Aboalhaija 78 Homeopathy History: Homeopathy was discovered by a German doctor, Samuel Hahnemann, who was looking for a way to reduce the damaging side effects associated with the medical treatment of his day, which included the use of poisons. He began experimenting on himself and a group of healthy volunteers, giving smaller and smaller medicinal doses, discovering that as well as reducing toxicity, the medicines became more effective as the doses were lowered. Al-Zaytoonah University Dr. Nour Aboalhaija 79 Homeopathy Principles  Like cures like  Dilution  Water remembers Al-Zaytoonah University Dr. Nour Aboalhaija 80 Homeopathy • Homeopathy is based on the principle of “like cures like” – that is, a substance which can cause symptoms when taken in large doses, can be used in small amounts to treat similar symptoms. • For example, drinking too much coffee can cause sleeplessness and agitation, so according to this principle, when made into a homeopathic medicine, it could be used to treat people suffering from sleeplessness and agitation. Al-Zaytoonah University Dr. Nour Aboalhaija 81 Homeopathy • This concept is sometimes used in conventional medicine. • for example, the stimulant Ritalin is used to treat patients with ADHD (Attention Deficit Hyperactivity Disorder) • small doses of allergens, such as pollen, are sometimes used to de-sensitise allergic patients. • An important difference with homeopathy however, is that the medicinal doses (known as remedies) are so small that toxic side-effects are avoided. Al-Zaytoonah University Dr. Nour Aboalhaija 82 Homeopathy As yet, science has not been able to explain the mechanism of action of ultra high dilutions in the body, but laboratory experiments have repeatedly demonstrated that homeopathically prepared substances cause biological effects. One theory is that during the production of a homeopathic medicine, the dilution and agitation processes cause an interaction between the original material and the water and alcohol it is mixed with. This creates tiny new structures (nanostructures) which are the ‘active ingredient’ and remain present even when the sample has been diluted many, many times. Al-Zaytoonah University Dr. Nour Aboalhaija 83 Homeopathy Al-Zaytoonah University Dr. Nour Aboalhaija 84 Homeopathy Homeopaths treat people based on genetic and personal health history, body type, and current physical, emotional, and mental symptoms. Patient visits tend to be lengthy. Treatments are “individualized” or tailored to each person. It is not uncommon for different people with the same condition to receive different treatments. Homeopathic remedies are derived from natural substances that come from plants, minerals, or animals. Common remedies include red onion, arnica (mountain herb), and Cinchona spp. Al-Zaytoonah University Dr. Nour Aboalhaija 85 Homeopathy The oral route is favored for homeopathic remedies, although ointments and creams are sometimes used especially for skin diseases. Most homeopaths usually give one remedy at a time. They claim that they are not sure what the effect of two remedies would be, or the interaction between them. Al-Zaytoonah University Dr. Nour Aboalhaija 86 Homeopathy  Uses of Homeopathic Remedies Historically, people have used homeopathy to maintain health and treat a wide range of long-term illnesses, such as • allergies, atopic dermatitis, rheumatoid arthritis, and irritable bowel syndrome. • minor injuries, such as cuts and muscle strains. Homeopathic treatment is not considered appropriate for illnesses, such as cancer, heart disease, major infections, or emergencies. Homeopathy has been widely used in India, England, and other European countries. Al-Zaytoonah University Dr. Nour Aboalhaija 87 Homeopathy Safety of Homeopathic Remedies Homeopathic remedies have been regulated in the United States since 1938 and are considered to be safe. Some criticizers of homeopathy believe that there is so little active substance in a solution that any benefits from treatment are likely not because of the substance but because you are thinking it is effective (placebo effect). Al-Zaytoonah University Dr. Nour Aboalhaija 88 Homeopathy Studies have tried to determine whether effects from homeopathic treatments are placebo or whether some other action occurs. Although these studies could not identify how homeopathic solutions work, there was evidence that homeopathic dilutions differ from placebos Al-Zaytoonah University Dr. Nour Aboalhaija 89 Introduction Selected examples of CAM Herbal medicine Homeopathy Aromatherapy Al-Zaytoonah University Dr. Nour Aboalhaija 90 AROMATHERAPY Aromatherapy is the therapeutic use of essential oils made from plants and flowers. It is a healing art that aims to refresh body, mind and spirit. • The different smells (aromas), and the chemical constituents of the oils, are said to produce different emotional and physiological reactions. • Although aromatherapy has been practiced in some form or another in various cultures for thousands of years, the modern version was developed mainly in France. Al-Zaytoonah University Dr. Nour Aboalhaija 91 AROMATHERAPY • Aromatherapy hasn’t yet undergone the same scientific study as other complementary therapies, but research so far shows that it can be an effective treatment for some complaints. • Used in a professional way, aromatherapy can never have any side or negative effects. • The psychic benefits aromatherapy particularly when accompanied by other pleasing sensory input, such as massage may create healing feelings that can modify disease processes or improve physiologic or functional deficits. Al-Zaytoonah University Dr. Nour Aboalhaija 92 AROMATHERAPY  Application of essential oils Some of the ways in which essential oils can be used include: • Massage: a small amount added to a vegetable-based oil. • Oil burner: a few drops vaporized in a burner. • Bath: half a dozen drops added to a full bath. • Inhalation: two to three drops added to a basin of hot water Al-Zaytoonah University Dr. Nour Aboalhaija 93 AROMATHERAPY  Application of essential oils  When using essential oils, it must be with a carrier oil.  The effect of carrier oil is different, for example: • Carrier oils that contain tocopherols (Vitamin E), for example, act as antioxidants, meaning they can extend the shelf life of the oil • while oils that contain essential fatty acids can have the opposite effect, making the oil prone to quicker rancidity. Al-Zaytoonah University Dr. Nour Aboalhaija 94 AROMATHERAPY  Application of essential oils  Carrier oils also differ in the type and amount of nutrients that they contain, their viscosity (thus affecting how they feel on your skin) and their aroma (thus affecting how they smell when mixed with essential oils).  Carrier Oils include: Sweet Almond (medium texture). Grape seed (light texture). Jojoba “a liquid wax” (silky texture nice for face). Al-Zaytoonah University Dr. Nour Aboalhaija 95 Al-Zaytoonah University Dr. Nour Aboalhaija 96 AROMATHERAPY  Mode of Actions of Aromatherapy pharmacological • essential oils enter the bloodstream. • oils react with enzymes & hormones psychological • How the body reacts to the scent • Effect on the mood Al-Zaytoonah University Dr. Nour Aboalhaija 97 AROMATHERAPY SPECIAL CONSIDERATIONS • Some people may be sensitive to essential oils • Some oils can irritate or burn the skin, while others can bring on an allergic reaction, such as a skin rash, in susceptible people. • For example: Eucalyptus oil, Ginger oil, Thyme oil, Black pepper oil. Al-Zaytoonah University Dr. Nour Aboalhaija 98 AROMATHERAPY SPECIAL CONSIDERATIONS • The majority of essential oils is irritant to skin (for this reason it should be diluted before the use) and they should never be swallowed (uncoated). • All essential oil should be avoided during the first trimester of pregnancy, because they can across easily the placenta reaching the fetus and causing harmful effect. Al-Zaytoonah University Dr. Nour Aboalhaija 99 AROMATHERAPY SPECIAL CONSIDERATIONS • Important factors to be considered • • • • • • Safety of oil Quality of oil Allergies Sensitivities Dilution Length of treatment Al-Zaytoonah University Dr. Nour Aboalhaija 100 AROMATHERAPY Therapeutic applications of aromatherapy. In aromatherapy the essential oils are used mainly in diluted form for certain conditions such as 1- Sleeping problems 2- Cold and Flu 3- Skin and hair parasites 4- Headache 5- Digestive problems Al-Zaytoonah University Dr. Nour Aboalhaija 101 AROMATHERAPY  Essential oils sold in pharmacy Sedative essential oils: they can be inhaled after dilution with a carrier oil or applied on skin Among the sedative essential oils we can find the following combination of Lavender, Mandarin, Sage and Chamomile. Al-Zaytoonah University Dr. Nour Aboalhaija 102 AROMATHERAPY  Essential oils sold in pharmacy Cold and flu The very famous and worldwide distributed ointment “ Vicks VapoRub” has several uses due its content of Menthol Eucalyptol Camphor Turpentine oil These volatile constituents are mixed with Vaseline to form a medical ointment with multiple uses including cold, flu, mosquito bites muscle pain Al-Zaytoonah University Dr. Nour Aboalhaija 103 AROMATHERAPY  Essential oils sold in pharmacy Skin and hair parasites Some essential oil are proven to have insecticidal and ovicidal activity such as Tea tree oil (terpenin-4-ol) Thyme (thymol and carvacrol) Rosemary (eucalyptol, borneol) Lemongrass (citral) Eucalyptus (eucalyptol) Citral is used also as mosquito repellent to prevent mosquito bite. Al-Zaytoonah University Dr. Nour Aboalhaija 104 Al-Zaytoonah University Dr. Nour Aboalhaija 105 0 1 2 2 3 4 5 6 1. Cardiovascular system 1.1. Heart Failure 1.1.1. Digitaloid 1.1.2. Hawthorn 1.2. Hypertension 1.2.1. Hawthorn 1.2.2. Garlic 1.2.3. Valerian 1.2.4. Rauwolfia 1.3. Chronic Venous Insufficiency 1.3.1. Horse chestnut 1.3.2. Butcher’s broom Al-Zaytoonah University Dr. Nour Aboalhaija 107 1. Cardiovascular system In the last 50 years, the global average of life expectancy at birth has increased with more than 20 years. With industrial development, in developed countries the major causes of disabilities death have shifted from a predominance of infectious diseases to chronic diseases such as cancer and cardiovascular diseases. The treatment of the latter is challenging, and the medication is based on synthetics.  Herbal preparations have major role in prevention and therapy. Al-Zaytoonah University Dr. Nour Aboalhaija 108 1. Cardiovascular system 1.1. Congestive heart failure (CHF) or Chronic cardiac insufficiency: Is one of the most common causes of death in the elderly population. The reduction of the pump function results in an insufficient oxygen supply to the organs, including the heart, leading to a wide range of symptoms (edema, cyanosis, tachycardia, hypertension and arrhythmia). Al-Zaytoonah University Dr. Nour Aboalhaija 109 1. Cardiovascular system 1.1. Congestive heart failure (CHF) or Chronic cardiac insufficiency: In the history of phytotherapy, a myocardial insufficiency was usually treated with cardiac glycosidecontaining plants. The most widely applied species for chronic cardiac failure belonged to the genus Digitalis. In acute cases, the quick-acting glycosides of Strophanthus seeds were used. More recently, pure Digitaloids have been used instead of the extracts of the plants since the narrow therapeutic range of the compounds may result in intoxications. Al-Zaytoonah University Dr. Nour Aboalhaija 110 1. Cardiovascular system 1.1. Congestive heart failure (CHF) or Chronic cardiac insufficiency: Although cardiac glycosides can be synthetized, for economic reasons they are still obtained by extraction from herbal raw material. The cornerstone of the efficacy of cardiac glycosides is the inhibition of Na+/K+/ATPase, which results in an increased intracellular Ca2+ level and an improvement of the heart muscle contraction (a positive inotrope effect). From among the “classical” phytomedicines, only one plant, hawthorn, is important in the treatment of a cardiac insufficiency. However, hawthorn has the major limitation that it is clinically effective only in mild and moderate cases. Al-Zaytoonah University Dr. Nour Aboalhaija 111 1. Cardiovascular system 1.1. Congestive heart failure (CHF) or Chronic cardiac insufficiency: inhibition of Na+/K+/ATPase Al-Zaytoonah University Dr. Nour Aboalhaija 112 1. Cardiovascular system 1.1.1. Hawthorn )‫(الزعرور‬ Dried flower-bearing branches of Crataegus monogyna. In the Middle Ages, several therapeutic indications were documented, ranging from the treatment of jaundice to use as a constipating agent. Hawthorn became one of the most important plants for the treatment of cardiovascular diseases in the second half of the 19th century, when an Irish doctor named Green used the plant (as part of a secret mixture) for the very successful treatment of different heart diseases. After his death, the main components of the remedy was revealed and since then, Crataegus is an essential part of the phytotherapy of cardiac insufficiency. Al-Zaytoonah University Dr. Nour Aboalhaija 113 1. Cardiovascular system 1.1.1. Hawthorn Chemical composition and mechanism of action The plant material contains proanthocyanidins as key constituents (13%). flavonoids, including flavones and flavonoles, mainly as glycosides, e.g. vitexin, hyperoside (0.1% in the fruits and 1% in the aerial parts) Triterpenes and aromatic amines. Al-Zaytoonah University Dr. Nour Aboalhaija procyanidin vitexin 114 1. Cardiovascular system 1.1.1. hawthorn Chemical composition and mechanism of action The most important effect of hawthorn is the positive inotropic activity. Ex vivo studies confirmed that Crataegus extracts significantly increase the force of contraction of the human myocardium. The extract of the plant inhibits Na+/K+ adenosine triphosphatase, leading to an increased intracellular Ca2+ level. Al-Zaytoonah University Dr. Nour Aboalhaija 115 1. Cardiovascular system 1.1.1. hawthorn Chemical composition and mechanism of action In an animal experiment, following the application of oral doses of 100 mg/kg for 12 weeks, the levels of serum cholesterol and triglycerides decreased significantly as compared with the control values. In a further experiment, i.v. administration of different Crataegus extracts resulted in a decrease of the blood pressure. Al-Zaytoonah University Dr. Nour Aboalhaija 116 1. Cardiovascular system 1.1.1. hawthorn Efficacy and indications the European Medicines Agency has granted a traditional-use monograph to the plant, with the following indications: o traditional herbal medicinal product used to relieve symptoms of temporary nervous cardiac complaints (e.g. palpitations, extra heart beat due to mild anxiety) after serious conditions have been excluded by a medical doctor. o traditional herbal medicinal product for the relief of mild symptoms of mental stress and to aid sleep. Typical daily doses are 0.25-1 g of the dry extracts, 1.5-5 g for the liquid extracts. Al-Zaytoonah University Dr. Nour Aboalhaija 117 1. Cardiovascular system 1.1.1. hawthorn Side-effects, interactions & contraindications Regarding its effect on the Na+/K+ pump, it may be presumed that hawthorn may potentiate the effect of digitalis glycosides, beta-blockers and other antihypertensives, but in human studies no such interactions have been recorded. Safety during pregnancy and lactation has not been established. In the absence of sufficient data, its use during pregnancy and lactation is not recommended. Al-Zaytoonah University Dr. Nour Aboalhaija 118 1. Cardiovascular system 1.2. Hypertension 1.2.2. Garlic  The cloves in the garlic bulb(Allium sativum) are used medicinally and as a food component. alliin Chemical composition and mechanism of action  Organic sulfur compounds such as alliin (allylcysteine sulfoxide) that are Pharmacologically active.  Allicin (diallyl-disuifide-S-oxide) and a variety of allicin byproducts, are formed when the garlic bulb is cut, chewed, or crushed – and they cause garlic’s distinctive aroma. Al-Zaytoonah University Dr. Nour Aboalhaija 119 1. Cardiovascular system 1.2.2. Garlic Efficacy and indications: Garlic may be helpful for high blood pressure, but the evidence is weak. Garlic showed strong antioxidant and radical-scavenging properties due to alliin content. Some studies indicate that certain groups of people who eat more garlic may be less likely to develop certain cancers, such as stomach and colon cancers. Al-Zaytoonah University Dr. Nour Aboalhaija 120 1. Cardiovascular system 1.2.3. Valerian  The dried rhizomes and roots of Valeriana officinalis Chemical composition and mechanism of action Alkaloids: Pyridine type; actinidine, valerianine and valerine. Steroids: β-sitosterol Volatile oil: , monoterpenes (camphene, borneol) and sesquiterpenes (valeranone, valerianol). Used as hypnotic (to treat sleep disorders), hypotensive agent and to treat anxiety and depression. Al-Zaytoonah University Dr. Nour Aboalhaija actinidine 121 1. Cardiovascular system 1.2.3. Valerian  Dosage: Dried rhizome/root: 1-3 g as an infusion or decoction up to 3 times daily Tincture: 3-5 ml (1:5; 70%) up to 3 times daily. Side effects: Sluggish feeling: A few people feel sluggish in the morning after taking valerian, especially at higher doses. Al-Zaytoonah University Dr. Nour Aboalhaija 122 1. Cardiovascular system 1.2.4. Rauwolfia Chemical constituents and therapeutic Effects: Dried rhizome and root of Rawolfia serpentine . Antihypertensive and sympatholytic effects due to various constituents, especially reserpine and ajmalicine. Contra-indications: In pregnancy and lactation. Al-Zaytoonah University Dr. Nour Aboalhaija 123 1. Cardiovascular system 1.3. Chronic Venous Insufficiency (CVI) Chronic venous insufficiency is a very common problem. The frequency of the disease increases with age, resulting in a deterioration of the quality of life, due to the symptoms relating to varicose veins and more serious consequences such as leg ulcer. Varicose veins develop as a result of the destruction of proteoglycans in the elastic tissue of the vein wall. This leads to dilation of the vessels and edema formation. Apart from surgical treatment, chronic venous insufficiency cannot be cured, but the symptoms may be relieved, and the process of vessel wall destruction may be slowed down. Al-Zaytoonah University Dr. Nour Aboalhaija 124 1. Cardiovascular system 1.3. Chronic Venous Insufficiency (CVI) Al-Zaytoonah University Dr. Nour Aboalhaija 125 1. Cardiovascular system 1.3. Chronic Venous Insufficiency (CVI) The pharmacotherapy of chronic venous insufficiency is usually based on the local or systemic application of natural or semisynthetic flavonoids. Several clinical studies have confirmed the efficacy of flavonoids in vasoprotection. However, despite their beneficial effects, these compounds are not essential, and hence they are not vitamins (so proposed the name vitamin P, i.e. permeability vitamin, for flavonoids). The aim of the treatment is to increase the capillary resistance and venous tone and relieve the symptoms.  This can be achieved by the application of flavonoids (in many cases “bioflavonoids” are applied, i.e. a flavonoid-rich fraction gained from different plants). Al-Zaytoonah University Dr. Nour Aboalhaija 126 1. Cardiovascular system 1.3. Chronic Venous Insufficiency (CVI) bilberry However, other secondary metabolites than flavonoids can also be useful in venous insufficiency. Some triterpene saponins also have a beneficial effect on vessel walls. Nevertheless, their mechanism of action is party different, involving the inhibition of certain enzymes that are responsible for the breakdown of the vein wall structure.  Flavonoid-containing plants are usually applied as industrial sources for bioflavonoids. The only plant of phytotherapeutic importance is bilberry. Among the saponin-containing plants, horse chestnut, and butcher's broom are the most significant. Because of the similar pathophysiological background, these herbs can also be used in the treatment of hemorrhoids. Al-Zaytoonah University Dr. Nour Aboalhaija 127 1. Cardiovascular system 1.3.1 Horse chestnut  Aesculus hippocastanum, a tree indigenous to Asia, was introduced to Europe by the Turkish invaders in the 16th century.  Horse chestnut was an important medicinal plant in the treatment of human and animals (especially horses). Today it is an ornamental tree that is cultivated worldwide.  In the Middle Ages, different plant parts were applied.  From the 19th century, the seeds gained primary importance in medicine.  Seed extracts were already used therapeutically in the early 1800s and there are several reports on their successful application in hemorrhoids.  The active constituents of the extracts were identified as saponins.  Traditionally, horse-chestnut extracts have been to treat edema, orally. Al-Zaytoonah University Dr. Nour Aboalhaija 128 1. Cardiovascular system 1.3.1 Horse chestnut Chemical composition and mechanism of action The seeds contain flavonoids, essential oil and sterols. Horse chestnut seeds contain 3-10% saponins (more than 30 different compounds). This saponin mixture is called aescin. Different experimentally induced edemas have been inhibited by the application of aescin in animals. Al-Zaytoonah University Dr. Nour Aboalhaija 129 1. Cardiovascular system 1.3.1 Horse chestnut Efficacy and indications  In a study on patients with varicose veins, oral administration of the extract decreased the activity of three types of hydrolase enzyme (betaN-acetylglucosaminidase, beta-glucuronidase and arylsulfatase) that catalyze the breakdown of the proteoglycans of the capillary walls.  On the basis of the clinical evidence, extracts standardized to 100 mg aescin may be applied orally as well-established medicines for the treatment of chronic venous insufficiency (characterized by swollen legs, varicose veins, a feeling of heaviness, pain, tiredness, itching, tension and cramps in the calves).  At least 4 weeks of treatment may be needed to achieve a beneficial effect. Al-Zaytoonah University Dr. Nour Aboalhaija 130 1. Cardiovascular system 1.3.1 Horse chestnut Al-Zaytoonah University Dr. Nour Aboalhaija 131 1. Cardiovascular system 1.3.1 Horse chestnut Side-effects, interactions & contraindications  In clinical trials, no treatment-related adverse events have been recorded.  Absolute contraindication of the treatment is limited to hypersensitivity to the active substance.  Saponins may have an irritative effect in the stomach, resulting in nausea. However, high tolerance has been demonstrated for controlledrelease dosage forms.  Although the hemolytic activity of saponins led to the suggestion that aescin might increase the effect of anti-coagulants, this was not confirmed by the clinical data.  Oral application is not intended for those under 18; for topical application, the age limit is 12 years. Al-Zaytoonah University Dr. Nour Aboalhaija 132 0 1 2 2 3 4 5 6 2. Central nervous system 2.1. Anxiety, sleeping disorders 2.1.1 Valerian 2.1.2 Hop 2.1.3 Lavender 2.1.4 Lemon balm 2.1.5 Passionflower 2.1.6 Oat 2.1.7 Motherwort 2.2 Depression 2.2.1 St. John’s wort Al-Zaytoonah University Dr. Nour Aboalhaija 134 2. Central nervous system Introduction • Anxiety, a depressed mood and sleeping disorders may be part of the normal life, but if these symptoms become permanent and affect the quality of life, psychotherapy and/or pharmacotherapy is indispensable. • These symptoms are often regarded as civilization diseases, since the increased level of stress and decreased physical activity may play a role in their development. • Some of these diseases (e.g. depression) were first described and defined in the 20th century. The availability of more sophisticated diagnostic methods and criteria have led to an increase in the number of patients by revealing the disease in previously undiagnozed patients. Al-Zaytoonah University Dr. Nour Aboalhaija 135 2. Central nervous system Introduction • Although the number and variety of synthetic antidepressants, antianxiety drugs and sleeping pills are rather high, there is a demand for more effective medicines with fewer side-effects. • The most important undesirable effects of sleeping pills and antianxiety drugs are dependence and increasing tolerance. • Antidepressants may have a wide range of side-effects, including obesity and a deterioration in the quality of life. • Herbal remedies usually have fewer undesirable effects, although their efficacy is inferior to that of synthetics. Al-Zaytoonah University Dr. Nour Aboalhaija 136 2. Central nervous system 2.1. Anxiety and sleeping disorders The symptoms of anxiety include discomfort, nervous tension and worry, and a sleeping disorder may also occur. Patients may additionally experience physical symptoms, e.g. gastrointestinal disturbances, headache or excessive sweating. All stressful and traumatic life events are normally accompanied by anxiety, but if the symptoms become exaggerated, treatment is needed. For an assessment of severity of the anxiety, the Generalized Anxiety Disorder Assessment (GAD 7) questionnaire may be used. This is a self-administered patient questionnaire which can be used even in pharmacies. Al-Zaytoonah University Dr. Nour Aboalhaija 137 2. Central nervous system 2.1. Anxiety and sleeping disorders The questions to be answered are the following: Over the last 2 weeks, how often have you been bothered by the following problems? 1. Feeling nervous, anxious or on edge 2. Not being able to sto