Pharmacy Students and Complementary Medicine PDF

Why should pharmacy students be interested in complementary and alternative medicine?  What is CAM? CAM is described as a group of diverse medical and health care systems, practices and products that are not currently considered to be part of conventional medicine. ...

Why should pharmacy students be interested in complementary and alternative medicine?  What is CAM? CAM is described as a group of diverse medical and health care systems, practices and products that are not currently considered to be part of conventional medicine.  What is CAM? Complementary and alternative medicine (CAM) is a term used to describe a wide range of healing systems that are not typically considered part of mainstream or conventional Western medicine. The goal of conventional medicine is to find the physical source of a particular disease and treat it. For example, if a person has an infection, a conventional doctor may prescribe an antibiotic to kill the invading bacteria. CAM practitioners, on the other hand, take a more "holistic" approach to health care. They believe that health and disease involve a complex interaction of physical, spiritual, mental, emotional, genetic, environmental, and social factors. In order to treat a disease or promote good health, CAM practitioners treat the whole person.  What does complementary medicine and alternative medicine mean? The terms "complementary medicine" and "alternative medicine" sometimes mean the same thing. But they have different implications. Complementary medicine refers to therapies used in combination with conventional medicine While alternative medicine is used in place of conventional medicine. An example of complementary medicine is using hypnotherapy (hypnosis) with pain medications to reduce anxiety and enhance relaxation in people recovering from severe burns. An example of alternative medicine would be following a special diet and taking herbs or vitamins rather than medications to treat attention deficit hyperactivity disorder (ADHD). What are the basic principles of CAM? Although CAM therapies vary widely, several themes can be traced through them all: The focus is on the whole person, the physical, emotional, social, and spiritual. Prevention of illness is a primary goal. Treatments are highly individualized. Treatments are aimed at the causes of illness rather than at its symptoms. Treatments are designed to support the natural healing processes of the body.  What is CAM? Though the terms “complementary” and “alternative” are often used together, they are not necessarily synonymous. Complementary therapies are often defined as therapies that are used alongside conventional medical therapies, while alternative approaches are generally thought of as being used instead of conventional methods. Using tai chi in addition to a prescription medicine for anxiety is an example of the former and seeing a homoeopath or herbalist instead of a GP an example of the latter.  There are hundreds of complementary therapies available, and the US National Institutes of Health (NIH) has categorized them according to five broad types : Healing systems (eg, ayurveda and traditional Chinese). These are complete sets of theories and practices. A healing system is not just a single practice or remedy — like massage — but many different practices that revolve around a philosophy or lifestyle, such as the power of nature or the presence of energy in the body. Mind-body connections (eg, biofeedback, hypnosis, meditation, relaxation, yoga). These techniques are intended to strengthen the communication between mind and body. CAM practitioners believe these two systems must be in harmony to maintain health.  There are hundreds of complementary therapies available, and the US National Institutes of Health (NIH) has categorized them according to five broad types: Dietary supplements (eg, vitamins, minerals, fish oil, glucosamine) and herbs (eg, echinacea, St John’s wort). Manipulation and touch (eg, acupressure, chiropractice, massage, osteopathy). These methods use human touch to move or manipulate a part of the body. Restoring natural energy forces (eg, acupuncture, magnet therapy, light therapy). Some CAM practitioners believe an energy force flows through the body. Although this force is invisible, if its flow is blocked or unbalanced, illness can result. These therapies aim to unblock or balance the energy force, and each one achieves this differently.  Manual therapies : Chiropractice Osteopathy Reflexology Massage  Chiropractice Chiro = done by hand. A method of treatment that manipulates body to relieve ( especially the spine ) and spinal joints low back pain or even headache or high blood pressure. Complementary Rx focuses on the spine as being integrally involved in maintaining health , providing primary to the nervous system as the primary coordination for function and health in body. Efficacy: Chiropractice treatment appears to be effective for muscle spasms of the back, neck, tension headache and some sorts of leg pain. Manipulations and alignment of vertebral joints leads to normal brain and nerve transmissions resorting and recovery the body from illness locating of eliminating subluxation.  How can a qualified practitioner be located? All 50 states, the District of Columbia, Puerto Rico, and the U.S. Virgin Islands recognize chiropractic as a health care profession. A chiropractic degree requires about the same number of classroom hours as a medical degree. The chiropractic program includes clinical experience, basic sciences, and standard, as well as structural (spinal) and functional (nervous system) diagnoses. At least one chiropractic organization serves each state in the U.S. The largest association is the American Chiropractic Association (ACA). The ACA can provide a list of licensed chiropractors in your area  Osteopathy (Osteo = bone , Pathy = disease) This method is somewhat similar to chiropractice and it is usually performed by the same practitioner, but the patient in case of osteopathy has a greater role. Definition: osteopathy is the diagnosis and treatment of pain and dysfunction in the musculo-skeletal system (dysfunction in muscles associated with a major bone or with a joint) due to mechanical problems. The effectiveness of such method is due to the increase in blood flow to nerves and organs, this will help organs to get rid of toxins and provide them the required energy for their function (especially heart & kidney). This method also activates the peripheral nervous system and organs associated with it.  Conditions benefiting from osteopathy: Backache; patients with disability due to serious injuries (from accidents or bad exercises), certain diseases or surgery will suffer from weakness in muscles. Such cases will benefit from both chiropractic (mainly applied on vertebrae) and osteopathy (mainly applied on muscles associated with bones {including vertebrae}) - Neck pain; directed mainly to the muscles of the neck rather than vertebrae. - Sport injuries; people who specialize in dealing with this type of injuries usually receive training courses in chiropractic, osteopathy, massage and first aid.  - Repetitive strains; result from repetitive use of certain part of the body, e.g. printers usually suffer from pain in the joints of their hands. Some types of headache such as tension headache (this type may benefit from chiropractic, reflexology as well as osteopathy).  Reflexology What is reflexology? Can it relieve stress? Reflexology is the application of pressure to areas on the feet, hands and ears. Reflexology is generally relaxing and may be an effective way to alleviate stress. The theory behind reflexology is that these areas correspond to organs and systems of the body. Proponents believe that pressure applied to these areas affects the organs and benefits the person's health. Reflexologists use foot charts to guide them as they apply pressure to specific areas. Sometimes these practitioners use items, such as rubber balls, rubber bands and sticks of wood, to assist in their work. Practitioners of reflexology include chiropractors, physical therapists and massage therapists, among others.  Reflexology Several studies funded by the National Cancer Institute and the National Institutes of Health indicate that reflexology may reduce pain and psychological symptoms, such as anxiety and depression, and enhance relaxation and sleep. Studies also show that reflexology may have benefits in palliative care of people with cancer. Reflexologists claim that reflexology also can treat a wide variety of medical conditions, such as asthma, diabetes and cancer. However, scientific evidence is lacking to support these claims. Reflexology is generally considered safe, although very vigorous pressure may cause discomfort for some people  Example on Healing systems: Traditional Chinese Medicine (TCM)  What is Traditional Chinese Medicine? Traditional Chinese Medicine (TCM) is a complete medical system that has been used to diagnose, treat, and prevent illnesses for more than 2,000 years. TCM is based on a belief in yin and yang, defined as opposing energies, such as earth and heaven, winter and summer, and happiness and sadness. When yin and yang are in balance, you feel relaxed and energized. Out of balance, however, yin and yang negatively affect your health. Practitioners also believe that there is a life force or energy, known as qi (pronounced "chee"healthy), in every body. For yin and yang to be balanced and for the body to be, qi must be balanced and flowing freely. When there is too little or too much qi in one of the body's energy pathways, called meridians, or when the flow of qi is blocked, it causes illness. The ultimate goal of TCM treatment is to balance yin and yang by promoting the natural flow of qi. In an interesting analogy, often used to explain its nature, qi is described as the wind in a sail, we do not see the wind directly, but we are aware of its presence as it fills the sail  Traditional Chinese Medicine (TCM) TCM is a type of complementary therapy which has been developed over thousands of years. China, the country of origin for such therapy, allocates specialized hospitals for TCM. TCM is a term used to describe a number of medical practices that originated in china. Encompasses large number of disciplines including acupuncture, Chinese Herbal medicine (plants used are those grow in china), dietary therapy, mind & body exercise, Meditation (TCM include about 350 disciplines but those are which has been approved by WHO).  Traditional Chinese Medicine (TCM) The philosophy of most complementary therapies (such as reflexology, chiropractic, osteopathy and homeopathy) has been evolved from TCM but with some modifications.  Traditional Chinese Medicine (TCM) The philosophy of TCM is the reestablishment of the balance between positive (yang) & negative (yin) energy. Yin (cold): illustrated by the dark part of the symbol, it is considered the active type of energy. Yang (hot): illustrated by the white part of the symbol, it is the nutritious type of energy which supports body functions. It is also associated with masculinity ‫طاقة‬.‫ذكرية‬ ‫الوخز باإلبر الصينية ‪Acupuncture‬‬  Acupuncture ‫الوخز باإلبر الصينية‬ Acu = perforation ( ‫الثقب‬ Puncture = piercing ‫ادخال االبرة‬ This type of complementary therapy includes a collection of procedures involving penetration of the skin with fine needles to stimulate certain points on the meridians ‫مسارات الطاقة‬ This will reestablish energy flow into the organs!!! The diagnosis in TCM is made by the observation of certain defects in some parts of the body resulted from an imbalance (due to blockage in the meridians) in the energy in such parts. Meridian is a path through which the +ve & -ve energy flows in opposite directions, it starts from the head and branches all over the body. Needles have been modified by adding a source of energy (thermal, magnetic, electrical, laser…). The length of the needles varies depending on the depth of the insertion point.  Acupuncture A part of Traditional Chinese Medicine (TCM) 36 States have state licensure for acupuncture 9-12 million visits to acupuncturists take place in the United States Acupuncture needles are regulated by the FDA as medical devices Clin Obstet Gynecol, 44(4), Dec. 2001, 801-813; Anat Record, 262, 2002, 257-265 Definitions Acupuncture: 2,000 acupuncture points on the body Connected via 12 main and 8 secondary pathways (Meridians) Meridians connect energy, qi (“chee”), between the surface of the body and the internal organs Qi regulates spiritual, emotional, mental and physical balance Qi is influenced by the opposing forces of yin and yang When yin and yang are balanced, they work with the natural flow of qi to keep the body healthy The placement of needles in the acupuncture points helps to keep the flow of qi unblocked.  Acupuncture Each of 12 primary meridians associated with and named for a specific organ Organs represent more than just the anatomic structures Approximately 360 acupuncture points lie along meridians Endorphins and cortisol are released with point stimulation Clin Obstet Gynecol, 44(4), Dec. 2001, 801-813; Anat Record, 262, 2002, 257-265 www.scienceandsociety.co.uk  CONTRAINDICATIONS of Acupuncture: 1-patient unwilling; may lead to paralysis if any sudden movement occurs during treatment. 2- patient at high risk of bleeding e.g. as a result of using antiplatelets or anticoagulants. 3- Patient with pacemaker, or who using any electrical device such as insulin pump. SIDE EFFECTS: 1. Hepatitis, HIV (inadequate sterilization , reusable needles). 2. Trauma: local hematoma at the site of needle insertion, it may be fatal if the insertion was close to the heart.  CONTRAINDICATIONS of Acupuncture: 3. Allergy to metallic needles; original needles were made from aluminum or copper but those were allergic for some patients, so they have been replaced by chrome or nickel. 4. Drowsiness (most common ), convulsions (in patients with history of any type of epilepsy even infantile spasms), fainting. 5. Cardiac arrhythmia Notes & precautions for acupuncture: 1. Patient should lie down during treatment, then the patient should sit for few minutes after the end of treatment session. 2. Disposable sterile needles to be used and should be counted prior and post treatment. 3. Observe for excessive bleeding after and through treatment Notes & precautions for acupuncture: Indications: 1. Back & knee pain. 2. Dental pain; sometimes acupuncture is used instead of local anesthetics. 3. Recurrent headache e.g. migraine 4. Smoking cessation (best indication) and other types of dependence or addiction (rehabilitation of addicts). 5. Weight loss. 6. Stroke (very effective). 7. GI problems; especially in IBS (irritable bowel syndrome,.) ‫(القولون العصبي‬  Chinese Herbal Medicine (CHM = Zhang Yao): CHM is one of the main disciplines of TCM in which thousands of environmental substances are used. CHM is also based on the philosophy of Yin-Yang. The prescription is usually prepared by combining many plants, animals or animal parts (Controversial; not preferred), minerals.  Chinese Herbal Medicine (CHM = Zhang Yao): The benefits of such combinations (rather than using one ingredient) are: 1. Increase efficacy (synergistic effect). 2. Decrease toxicity & side effects. 3. Accommodate complex clinical situations. 4. Alter the action of other substances (some substances are added just to improve the action of other ingredients in the combination).  Definitions Diet supplement--product (other than tobacco) that is intended to supplement the diet containing one or more of the dietary ingredients listed here: vitamin, mineral, an herb or other botanical, an amino acid a dietary supplement used by humans to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract or combination of any ingredient described above DSHEA--Dietary Supplement Health and Education Act, passed in October, 1994; allowed for labeling and selling of dietary supplements with little to no oversight by the FDA Clin Obstet Gynecol, 44(4), Dec. 2001, 780-788 The role of pharmacist in CAM Diagnostic procedure is a delicate and complicated process; it takes 40-60 minutes because it deals with the body as a whole. Methods of diagnosis are: 1. Listening to Quality of voice & breath; so clinics should be isolated completely from sounds. 2. Asking certain questions about patient life style & his/her disease. 3. Observing patient general emotions and assessing quality of skin (texture & color). 4. Palpation of pulse and body (Vital Signs)  Dispensing: Chinese herbal formula (only plants & minerals are used in the western developed countries) at CHM pharmacy comprises the following four main components: 1. Main ingredient (may contain 2-3 plants); the active ingredient which usually constitutes most of quantity. 2. Associate ingredient; to assist the main ingredient (increase efficacy). 3. Adjuvant ingredient (amount less than associate ingredient); acting as enhancer of the main ingredient (either by synergistic effect or by decreasing toxicity of the main ingredient). 4. Guide ingredient; focuses on the actions of the whole formula with specific effects on Meridians.  Considering Aromatherapy Aromatherapy Defined Aromatherapy is the practice of using the natural oils extracted from flowers, bark, stems, leaves, roots or other parts of a plant to enhance psychological and physical well-being. Aromatherapy Defined The inhaled aroma from these "essential" oils is widely believed to stimulate brain function. Essential oils can also be absorbed through the skin, where they travel through the bloodstream and can promote whole-body healing. A form of alternative medicine, aromatherapy is gaining momentum. ‫تطور وتزداد اهميتها‬ It is used for a variety of applications, including pain relief, mood enhancement and increased cognitive function.  The Benefits of Aromatherapy contd With complete perspective, preventive health care and useful complementary treatment Essential oils have antiseptic, and some have antiviral, anti inflammatory, pain relieving, antidepressant, stimulation, relaxation, digestion improvement, diuretic properties and expectorant properties. widely used at home, clinics and hospitals. How does Aromatherapy work?  How does Aromatherapy work? The effects of an aroma can be relaxing or stimulating. Work at psychological, physiological, and cellular levels. affect body, mind and all the delicate links in between Produced Only steam distillation or expression or squeezing methods.  Methods of application Three ways: through ingestion, through olfaction, the fastest effect, triggers olfactory sense and trigger responses in limbic system. through topical application, via diffusion, compression, massage. Methods of application massage: Oils penetrate the skin and are absorbed into the body fluids and bloodstream to work internally aroma alone: Believed to have the quickest beneficial effect, as smell has been shown to have an immediate effect on the brain, almost instantly releasing desired hormones inhalation: Helps clear the head, again working on the brain adding to baths: Working at two levels, by inhalation and by absorption into the skin by use of skin products, compresses etc Effects and ways oils are used 1) stimulating: to refresh the body and raise the spirits 2) sedative: to relax and calm the body and mind 3) regulating: to regulate the main bodily functions 4) euphoric: to uplift emotions 5 Aromatherapy Oils Everyone Should Have at Home 1. Lavender. Lavender oil has a calming effect which does wonders for those suffering from anxiety. Medicinally, it can be used as an antiseptic and pain reliever to soothe minor burns, insect bites and stings, and muscle or joint pain. 2. Peppermint. Peppermint oil has a very stimulating yet soothing aroma and is what I like to call “mother nature’s Icy Hot” due to its main constituent, menthol which is it effective in arousing your mental sharpness but it can be used to relieve congestion, headaches, migraines, digestive problems, and soothe achy muscles.it can be typically used to get rid of headaches or to relieve muscle soreness by diluting it with a carrier oil, like grape seed oil, and rubbing it into whatever is sore. 5 Aromatherapy Oils Everyone Should Have at Home 3. Eucalyptus. This oil has a very fresh and clean aroma that is sure to open your airways up. Eucalyptus oil is anti-everything, and for once that’s a good thing. It is a natural antibacterial, antifungal, antimicrobial, antiviral, and anti-inflammatory. It is best used for respiratory problems like colds, coughs, asthma, and congestion in addition to wounds, muscle pain, mental exhaustion, dental care, and skin care. 4. Lemon. With its uplifting and fresh scent, lemon oil can help get rid of bad feelings and increase concentration and mental awareness. It is also an antiseptic and antifungal 5 Aromatherapy Oils Everyone Should Have at Home 5. Tea Tree. A widely popular form of alternative medicine, tea tree oil is awesome! Not only is tea tree oil’s astringent properties great for alleviating oily secretions of the skin – think oily face & scalp issues – but it’s terpinen content soothes minor wounds without irritation. add a few drops to your shampoo prior to washing; it leaves my scalp clean.  Tea tree oil Origin: is the pale yellow volatile oil distilled with steam from the leaves of several species of Melaleuca australian trees : Myrtaceae The Australians have used the tea tree as a remedy for cuts, burns and insect bites Contents: Volatile oil: cineole, terpinen-4-ol, α-terpineol and linalool Uses: topical antibacterial and antifungal agent in various vaginal and skin infections and acne vulgaris. Tea tree oil is toxic when taken orally Patient advised to 1) Never eat or drink pure V.O unless under medical supervision ( mouth wash and gargles should never be swallowed ). 2) Never use concentrated V.O directly on the skin ( typical dilution 15 drops : 50 ml of carrier oil. 3) Some oils might react with sunlight and burn skin ( lemon ,orange). Patient advised to 4) Infants , pregnant , elderly , kidney or liver diseased pt , are at high risk of toxicity 5) Don’t use homeopathic remedies concurrently with aromatherapy. 6) Rate of absorbance increase with increased temp. of skin , pressure of water ( showers with soap ). Note : oils safe to be used by pregnant : lavender and ginger oils which may be used to relief nausea , motion sickness and even burns also chamomile. Homeopathy  What is homeopathy? Homeopathy is derived from the Greek words for "like" and "suffering." The guiding principle behind homeopathy is "like cures like," originates from Egypt and ancient Greece. In the late 18th century, a German physician named Samuel Hahnemann read that quinine-containing Peruvian bark (chinchona) cured malaria. Hahnemann swallowed a dose of Peruvian bark and began to feel feverish, drowsy, extremely thirsty, and agitated, which are all symptoms of malaria. Hahnemann started to experiment more and formed his theory that like cures like, or the Law of Similars: that when a substance in large doses causes certain symptoms, in small doses it can cure these same symptoms.  Herbs and other plants, minerals, venom from snakes, and other substances can be used to make homeopathic remedies. They are diluted again and again and "succussed" or shaken vigorously between each dilution. The process of sequential dilution and succussion is called potentization. Succussed (Definition): (in preparing homeopathic remedies) shake (a solution) vigorously.  Definitions Homeopathy--System of therapy developed by Samuel Hahnemann based on the “law of similia”, ‫مبدأ التشابه‬ from the aphorism ‫المقولة الالتينية‬, simila similibus curantur (likes are cured by likes), which holds that a medicinal substance that can evoke certain symptoms in healthy individuals may be effective in the treatment of illnesses having symptoms closely resembling those produced by the substance Therapy mediated through the potentiation of substances which are prepared with serial dilutions, often to the point in which no molecules of the active substance is detectable Flourished during the 1800’s when patients often did better than those treated with blood letting, emetics and other treatments. Homeopathic preparation Rhus toxicodendron, derived from poison ivy How can pharmacists be involved in CAM? The most obvious involvement for pharmacists in CAM is through the sale of products such as dietary supplements, herbal medicines, homoeopathic remedies and aromatherapy oils. However, as in other areas of pharmacy practice, pharmacists’ role could extend beyond products. Pharmacists can be involved in: Providing information on the appropriate use of CAM. This should include not only those products sold in the pharmacy but also those products and therapies received by patients outside of the pharmacy. Asking customers questions about their use of CAM. Being aware of potential adverse reactions and interactions with conventional medicines. How can pharmacists be involved in CAM? Providing information Pharmacists should only provide information on complementary medicines and therapies to the level at which they are trained and competent. The Royal Pharmaceutical Society Code of Ethics makes this quite clear. It states: “The public trusts pharmacists to offer informed advice on treatments and medicines, and the profession expects pharmacists to ensure that they are competent in any area in which such advice is given. Pharmacists providing homoeopathic medicines or other complementary therapies have a professional responsibility: How can pharmacists be involved in CAM? To ensure that stocks of homoeopathic medicines or herbal medicines or other complementary therapies are obtained from a reputable source of supply Not to recommend any remedy where they have any reason to doubt its safety or quality Only to offer advice on homeopathic or herbal medicines or other complementary therapies or medicines if they have undertaken suitable training or have specialized knowledge.”  The British Register of Complementary Practitioners has a list of practitioners registered according to the different disciplines (see www.icmedicine.co.uk), and is currently the best overall guide to appropriately qualified practitioners.  CAM therapies may also have adverse effects and may influence the progression of a disease or have implications for the outcome of conventional therapy. Use of CAM may also delay a proper medical diagnosis of an illness or influence adherence to prescribed medication. Patients are often wary of telling health care professionals that they are using CAM, and if pharmacists are to contribute to the wise use of these therapies, they must be non- judgemental in their approach.  Questions Questions about CAM should form part of any medication review or response to symptoms in the pharmacy. It is important to be aware that patients may be using CAM in addition to, or instead of, conventional treatments. This is most likely when conventional treatments offer little hope of a cure (eg, in cancer or AIDS), are associated with serious side effects (eg, chemotherapy) or when the condition is not easily managed by conventional medicine (eg, insomnia, back pain). Herbal drug interactions I. INTRODUCTION. Many of the drugs available on the market are derived from plants. Some of those include aspirin, atropine, belladonna, capsaicin, cascara, colchicine, digoxin, ephedrine, ergotamine, ipecac, opium, physostigmine, pilocarpine, podophyllum, psyllium, quinidine, reserpine, scopolamine, senna, paclitaxel, tubocurarine, vinblastine, and vincristine. Herb products are also derived from plants; however, these products are considered drugs by the U.S. Food and Drug Administration (FDA). A. Regulations 1. The Federal Food, Drug, and Cosmetic Act of 1938 mandated pharmaceutical companies to test drugs for safety before marketing. 2. The Kefauver–Harris Drug Amendments of 1962 mandated pharmaceutical companies to test drugs for efficacy before marketing. Food and Drug Administration (FDA). A. Regulations 3. The Dietary Supplement Health and Education Act of 1994 mandated the following: a. Dietary supplements are not drugs or food. They are intended to supplement the diet. b. Herbs are considered dietary supplements. c. Dietary supplements do not have to be standardized. d. The secretary of Health and Human Services may remove a supplement from the market only when it has been shown to be hazardous to health. e. Dietary supplements may make claims only regarding the effects on structure or function of the body. No claims regarding a particular disease or condition may be made. f. The following statement is required on the product label: “This product has not been evaluated by the FDA. It is not intended to diagnose, treat, cure, or prevent a disease.” This product has not been evaluated by the FDA. It is not intended to diagnose, treat, cure, or prevent a disease. Food and Drug Administration (FDA). A. Regulations 4. Final rule for Current Good Manufacturing Practices (CGMPs) for dietary supplements (2007) a. Manufacturers are required to evaluate for identity, purity, strength, composition 5. German Federal Health Agency a. In 1978, the German Federal Health Agency established Commission E. b. Commission E evaluates the safety and efficacy of herbs through clinical trials and cases published in scientific literature. c. There are 380 published monographs on herbs. HERBAL–DRUG INTERACTIONS A. Herbal preparations are various combinations of herbs, sometimes being one herb, or a combination of herbs. 1. Herbal preparations generally contain several different pharmacologically active alkaloids or other active constituents. For example, St. John’s wort has at least six different constituents: hyperforin, biapigenin, hypericin, quercetin, chlorogenic acid, and pseudohypericin. Each constituent has its own metabolism, binding, and pharmacologic action. HERBAL–DRUG INTERACTIONS The predominant effect or interaction depends on the relative potency of each constituent in the herb. For example, the constituents of St. John’s wort have inhibitory activity of the CYP450 isoenzymes 3A4, 2C9, 1A2, 2D6, and 2D9, but none of these effects are considered clinically significant. St. John’s wort appears overall to be an inducer of CYP3A4, and its constituents have many additional effects on metabolism and binding sites. 2. Herbal preparations with the same name, for example, St John’s wort, marketed by different manufacturers do not have equivalent amounts of each constituent. The USP-NF is attempting to create quality standards for these preparations. HERBAL–DRUG INTERACTIONS 3. Many herbal drugs interact at the same transport, metabolism, and receptor sites as traditional prescription drugs (Table 13-6). 4. Traditional Chinese medicine (TCM) may contain a combination of herbs. Some imported TCM products have been found to contain unlisted legend drugs. An example is a TCM medication advertised to treat diabetes that was found to contain the pharmaceuticals glyburide and phenformin. 5. Some herbal preparations may contain unrecognized contaminants such as heavy metals or a similar-appearing herb that is mistakenly harvested. These quality control issues are to a large extent unregulated by government agencies. Cardiovascular System  Phytomedicines and Cardiovascular diseases Phytomedicines play a significant role in the treatment of mild forms of heart failure and coronary insufficiency, in the prevention and treatment of atherosclerosis and its sequelae, and in the symptomatic treatment of chronic venous insufficiency. The pharmacologic therapy of heart failure is based on three principles: Increasing the efficiency of the heart muscle (cardiac glycosides), Reducing the preload (diuretics), Reducing the afterload (vasodilators, ACE inhibitors). But cardiac glycosides and other positive inotropic agents ( also shorten the refractory period, thereby increasing the risk of cardiac arrhythmias  THE STORY OF FOXGLOVES A old woman in Shrospshire (England) used to prescribe a secret cure for the treatment of dropsy and other cardiac diseases. This secret recipe was found to contain foxgloves (Digitalis purpurea). William Withering, the English physician and botanist after getting the hint from the old lady, used the herb and observed that foxglove has a power over the motion of the heart, to a degree yet unobserved in only other medicine. Powdered foxgloves, and its active constituents Digoxin and, Digitoxin, are now among the most widely prescribed medicines for heart patients.  O O R CH3 Digitoxin: R = H CH3 H Digoxin: R = OH CH3 H OH O O CH3 H O O CH3 OH O O OH HO OH  There are only a few herbs, however, for which safety and efficacy have been adequately proven: Hawthorn (heart failure and coronary insufficiency) Garlic (atherosclerosis), Ginkgo extract (arterial occlusive disease), Horse chestnut extract (chronic venous insufficiency). Herbal remedies for angina pectoris, cardiac arrhythmias, and hypertension and hypotension.  Heart Failure and Coronary Insufficiency The classic remedies used to treat myocardial insufficiency are the cardiac glycosides derived from purple and Grecian foxglove (Digitalis species). These compounds are colorless, bitter- tasting substances that cause local irritation. Their chemical compositions are known, and they can be synthetically produced, but for economic reasons the 14 pure glycosides or their precursors are still obtained by extraction from digitalis leaf.  Because the cardiac glycosides are specific, identifiable chemical compounds that have a narrow therapeutic dose range, they are not considered phytotherapeutic agents and are outside the realm of herbal medicine. Galenic preparations made from digitalis leaves are obsolete in modern pharmacotherapy. Details on the pure glycosides and their actions can be found in textbooks of pharmacology.  Hawthorn ‫الزعرور‬ Hawthorn (Crataegus species) has been used to treat heart disease as far back as the 1st century. By the early 1800s, American doctors were using it to treat circulatory disorders and respiratory illnesses. Traditionally, the berries were used to treat heart problems ranging from irregular heartbeat, high blood pressure, chest pain, hardening of the arteries, and heart failure. Today, the leaves and flowers are used medicinally. There is even research to suggest that hawthorn might be effective when used in the treatment of mild-to-moderate heart failure.  Hawthorn Animal and laboratory studies report hawthorn contains antioxidants, including oligomeric procyandins (OPCs, also found in grapes) and quercetin. Antioxidants are substances that destroy free radicals, which are compounds in the body that damage cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body and grow in number as we age. Environmental toxins (including ultraviolet light, radiation, smoking, some medicines, and air pollution) can also increase the number of these damaging particles. Scientists believe free radicals contribute to the aging process (such as wrinkling), as well as the development of a number of health problems, including cancer and heart disease. Antioxidants in hawthorn may help stop some of the damage from free radicals, especially when it comes to heart disease.  Flowering branch of hawthorn (Crataegus species). Hawthorn is a member of the Rosaceae family, but the unpleasant aroma of its blossoms attracts only flies. The tall shrubs are distributed throughout Europe  What is it Made Of? Hawthorn contains many substances that may benefit the heart. These antioxidant flavonoids, including oligomeric procyandins (OPCs, also found in grapes) , may help dilate blood vessels, improve blood flow, and protect blood vessels from damage. The berries, leaves, and flowers of the hawthorn plant have been used for medicinal purposes. Most modern preparations use the leaves and flowers, which are believed to contain more flavonoids than the berries.  Medicinal Uses and Indications Hawthorn is used to help protect against heart disease and help control high blood pressure and high cholesterol. Both animal and human studies suggest hawthorn increases coronary artery blood flow, improves circulation, and lowers blood pressure. It has also been used on the skin to treat boils and skin sores. Heart failure Hawthorn has been studied in people with heart failure (a condition in which the heart is unable to pump enough blood to other organs in the body).  The updated 1994 Commission E monograph on hawthorn leaves and flowers states that the extract is indicated for "declining cardiac performance consistent with stage II failure according to NYHA criteria." The recommended dosage is 160-900 mg/day of the crude water-and-alcohol extract with a designated content of flavonoids (4-20 mg) or oligomeric procyanidins (30-160 mg). Hawthorn preparations should be taken orally and should be continued for at least 6 weeks. Side effects of Hawthorn are rare, but may include headache, nausea, and palpitations (a feeling of a racing heart).  Possible Interactions Digoxin: Hawthorn may enhance the activity of digoxin, a medication used for irregular heart rhythms. Beta-blockers: These drugs are used to treat heart disease by lowering blood pressure and dilating blood vessels. Hawthorn can make the effects of these drugs stronger. They include: Atenolol (Tenormin) Metoprolol (Lopressor, Toprol-XL) Propranolol (Inderal, Inderal LA) Calcium channel blockers (CCBs): These drugs are used to treat high blood pressure and angina by dilating blood vessels. Hawthorn can make the effects of these drugs stronger. They include: Norvasc (amlodipine) Cardizem (diltiazem) Procardia (nifedipine)  Possible Interactions Phenylephrine: In a laboratory study, an alcoholic extract of hawthorn fruit reduced the effects of phenylephrine, a medication that constricts blood vessels and is commonly found in nasal decongestant products. Medications for male sexual dysfunction (Phosphodiesterase-5 inhibitors): When used together with Hawthorn, it may result in blood pressure dropping too low. Nitrates: These medications increase blood flow to the heart and taking Hawthorn together with them might increase the chance of dizziness or light headedness.  Garlic (atherosclerosis), Overview Garlic has been used as both food and medicine for thousands of years, dating back to when the Egyptian pyramids were built. In early 18th century France, gravediggers drank crushed garlic in wine believing it would protect them from the plague ‫الطاعون‬. During both World War I and II, soldiers were given garlic to prevent gangrene. It was also used as an antiseptic and applied to wounds to prevent infection.  Garlic (atherosclerosis) Overview Today garlic is used to help prevent heart disease, including atherosclerosis or hardening of the arteries (plaque buildup in the arteries that can block the flow of blood and may lead to heart attack or stroke), high cholesterol, high blood pressure, and to boost the immune system. Eating garlic regularly may also help protect against cancer.  Garlic Claims: Antibiotic, antiviral, general cure all, lowering of blood pressure, cholesterol, and regulation of circulatory system.  Garlic Well studied herb. – Shown to lower cholestreol by 9-12% in 8-16 weeks of use. – May also possess antibiotic activities. – Large doses may cause heartburn. Garlic Used in Europe as an approved remedy for cardiovascular conditions and for the use of the flu and colds.  The conditions for which garlic is showing the most promise include the Heart disease following: Garlic is most often mentioned as an herb for heart disease and atherosclerosis (hardening of the arteries). But evidence is mixed. Some studies suggest that garlic may help prevent heart disease. It may slow down atherosclerosis and lower blood pressure a little, between 5% and 8%. Most of the studies on high blood pressure use a specific formulation called Kwai. One study that lasted 4 years found that people who took 900 mg daily of standardized garlic powder slowed the development of atherosclerosis. Garlic also seems to act as a blood thinner, which may help prevent heart attacks and strokes.  The conditions for which garlic is showing the most promise include the following: Common cold Early evidence suggests garlic may help prevent colds. In one study, people took either garlic supplements or placebo for 12 weeks during cold season, between November and February. Those who took garlic had fewer colds than those who took placebo. And when they did get a cold, the people taking garlic saw their symptoms go away faster than those who took placebo.  The conditions for which garlic is showing the most promise include the following: Cancer Garlic may strengthen the immune system, helping the body fight diseases such as cancer. In test tubes, garlic seems to kill cancer cells. population studies, ones that follow groups of people over time, suggest that people who eat more raw or cooked garlic are less likely to get colon and stomach cancers and cancer of the esophagus. In fact, researchers who reviewed 7 studies found a 30% reduction in risk of colorectal cancer among people who ate a lot of raw or cooked garlic. Garlic supplements do not seem to have the same effect.  The conditions for which garlic is showing the most promise include the following: Cancer A large-scale study, called the Iowa Women's Health Study, looked at how much garlic, fruit, and vegetables were in the diets of 41,000 middle-aged women. Results showed that women who regularly ate garlic, fruits, and vegetables had a 35% lower risk of developing colon cancer. Garlic may help the immune system function better during times of need such as in cancer. In a study of 50 people with inoperable colorectal, liver, or pancreatic cancer, immune activity improved after they took aged garlic extract for 6 months  Horse chestnut extract Aesculus hippocastanum Also known as buckeye and Spanish chestnut, the seeds, leaves, bark and flowers of horse chestnut trees have long been used medicinally. The trees are native to Eastern Europe but can be found throughout the Northern Hemisphere. Horse chestnut extract Though it is sometimes referred to as buckeye, it is not the same species as that of buckeye trees that grow in Ohio and California.  Be careful not to confuse aesculus hippocastanum (Horse chestnut) with aesculus californica (California buckeye) or aesculus glabra (Ohio buckeye). Some people call any of these plants horse chestnut. This information applies to aesculus hippocastanum.  Medicinal uses Horse chestnut seed extract has been extensively studied for chronic venous insufficiency (CVI), a circulation problem in which the veins do not efficiently return blood from the legs to the heart. This condition is associated with varicose veins, pain, ankle swelling, itching, and nighttime leg cramping. A review of all the clinical trials concluded that the evidence suggests that horse chestnut seed extract is an efficacious and safe short-term treatment for CVI. One study actually found it as effective as compression stockings.  Dose Horse chestnut seed extract is also used to treat hemorrhoids. One small study showed that horse chestnut extract providing 120 mg of horse chestnut seed extract per day significantly improved symptoms of pain, itching, burning, and swelling. Available in: Extracts standardized to contain 16 to 20 percent aescin.  How does it work? Horse chestnut contains a substance that thins the blood. It also makes it harder for fluid to leak out of veins and capillaries and weakly promotes fluid loss through the urine to help prevent water retention (edema).  Herb / drug interactions: Horse chestnut extract might slow blood clotting, increasing the risk of bruising and bleeding in people taking aspirin, ibuprofen, coumadin or other drugs that slow clotting. Horse chestnut may slow the process by which the body eliminates lithium, a drug used to treat the manic side of bipolar disorder. This effect could lead to serious side effects. Horse chestnut may lower blood sugar, which could amplify the effects of drugs that lower blood sugar in people with diabetes. Cardiovascular System- Part 2  Hypotension and Hypertension Hypotension and hypertension are not considered primary indications for phytotherapy. Nevertheless, some herbal medications are suitable for short-term use in the symptomatic treatment of orthostatic complaints associated with low blood pressure and for longer-term use as a supportive therapy in patients with high blood prssure  Hypotension and Hypertension Hypotension ordinarily refers to blood pressures less than 100 mm Hg systolic and 60 mm Hg diastolic. Low blood pressure has no pathologic significance in itself and is even beneficial in inhibiting atherosclerotic disease. Hypotension requires treatment only if it is associated with orthostatic symptoms such as dizziness, grogginess, headache, and fatigue.  Caffeine Caffeine and caffeine-containing beverages are agents with unpredictable antihypotensive effects. It is a common experience, however, for people with low blood pressure to feel better after drinking their morning coffee or tea. Caffeine and other methylxanthines act directly on the pressor centers of the circulatory system; they also exert mild positive inotropic and chronotropic effects on the heart. Their duration of action is approximately 1-3 h.  A morning coffee infusion is prepared with 5-8 g of roasted coffee per cup (150 mL). Roasted coffee has a caffeine content of about 1-2 %, so a total of about 100 mg of caffeine is ingested in one cup of coffee. Dried tea leaves contain 2-5 % caffeine. But given the smaller amount of herb that is used, and the method of extraction (infusion) one cup of black tea contains only about 30-50 mg of caffeine.  Other caffeine-containing herbs are guarana seeds, cola seeds, mate leaves, and cocoa beans. The amounts of methylxanthines contained in these herbs are shown in Table 3.3.. cola seeds  Purine alkaloids Theobromine, which is the least used compound of them medicinally; the only difference found is that the nitrogen atom number 1 loses its methyl group so it will be named 3,7- dimethylxanthine. There is a resemblance in the biological structure between theobromine and theophylline but differs in the potency, in theobromine the nitrogen atom number 1 loses its methyl group while in theophylline nitrogen atom number 7 loses its methyl group  mate leaves lso known as yerba mate, is a traditional South American caffeine- rich infused drink, particularly in Argentina (where it is defined by law as the "national infusion"), Uruguay, Paraguay, the Bolivian Chaco, and Southern Brazil. It is also consumed in Syria, the largest importer in the world, and by the Druze in Lebanon  mate leaves Researchers from NCI (National Cancer Institutes) and Brazil found both cold- and hot-water extractions of popular commercial yerba mate products contained high levels (8.03 to 53.3 ng/g dry leaves) of carcinogenic polycyclic aromatic hydrocarbons (PAHs) (i.e. benzo[a]pyrene). However, these potential carcinogenic compounds originated from the commercial drying process of the mate leaves, which involves smoke from the burning of wood, much like polycyclic aromatic hydrocarbons found in wood- smoked meat. "Unsmoked" or steamed varieties of yerba mate tea are also available.  Guarana Is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for the seeds from its fruit, which are about the size of a coffee bean. As a dietary supplement, guarana is an effective stimulant: its seeds contain about twice the concentration of caffeine found in coffee seeds (about 2–4.5% caffeine in guarana seeds compared to 1–2% for coffee seeds).  Extracts from guarana and cola seeds are sold over the counter in the form of chewable tablets or drink mixtures. Due to the unpredictable risks, especially to children and adolescents (lethal caffeine dose between 3 and 10 g!), efforts are being made to restrict the over-the-counter availability of guarana products. Caffeine is lipid-soluble, so it is readily absorbed from the gastrointestinal tract  **In the 1800s, coca drinks were fashionable (like a black tea), a pharmacist invented Coca-Cola he is the father of Cocacola , he used coca leaves and the cola seeds[coca: providing cocaine, and cola: supplying caffeine, and its red color was due to tannins ,the coca content was omitted from 1906 onwards because of physiological dependence also pharmacological studies showed that cocaine is addictive drug , but the name and popularity continue.(now contains cola extract only).  The monographs state that caffeine and caffeine- containing herbs are useful for the short-term relief of symptoms due to mental or physical fatigue. None of the monographs address the treatment of hypotension or orthostatic complaints, but we know from experience that many hypotensive patients respond positively to caffeine and caffeine-containing herbs. The possible side effects of caffeine-containing herbs include stomach upset, nervousness, and sleeplessness.  Oleander Leaves The crude drug consists of the dried leaves of Nerium oleander. Native to the Mediterranean, oleander derives its species name from the similarity of the shape of leaves to those of the olive tree. The cardioactive glycoside fraction of oleander leaves is dominated by oleandrin, whose aglycone is closely related to the gitoxin of the purple foxglove. Commission E in 1988 monograph did not recommend oleander extract as a medicinal agent, ‫‪Nerium oleander‬‬ ‫الدفلى أو الدفلى الزيتية‬  In 1993 the Commission did ascribe therapeutic value to a fixed combination of false liquid extract, lily-of-the-valley powdered extract, squill powdered extract, and oleander- leaf powdered extract based on clinical studies of the commercial product (Miroton). Seda-Miroton: a cardiac drug and psychopharmacologic agent The indication was described as "mild forms of heart failure with circulatory lability." The following contraindications were noted: NYHA stage III or IV heart failure, treatment with digitalis glycosides, digitalis intoxication, hypercalcemia, potassium deficiency states, bradycardia, and ventricular tachycardia.  Nerium oleander Common name: ‫دفلة‬ Scientific name: Nerium oleander L. Family: Apocynaceae plant52  Phytotherapy of Hypertension According to the WHO definition, hypertension is present when the blood pressure exceeds 160 mm Hg systolic and 95 mm Hg diastolic. Blood pressures in the range of 140-160 systolic and 90-95 diastolic are classified as borderline hypertension, which is usually managed by nonpharmacologic means (weight loss, low-salt diet, exercise).  Phytotherapy of Hypertension An herbal remedy that has been used in the treatment of mild to moderate hypertension is the whole extract made from the dried roots of Indian snakeroot (Rauwolfia serpentina) indian snake family Apocynaceae, an evergreen shrub native to tropical Asia. Reserpine  The extract contains more than 50 different alkaloids, including the sympatholytic agent reserpine. Reserpine is not only one of the oldest antihypertensive agents, it is still one of the most economical. Because of its association with objectionable side effects, particularly at doses higher than 0.2 mglday (depression, fatigue, impotence, nasal stuffiness), the use of reserpine has declined in industrialized countries, but it is still included as a standard antihypertensive agent in the WHO list of essential drugs. Because reserpine is an isolated compound with a known chemical composition, it is not considered a phytotherapeutic agent.  Phytotherapy of Hypertension It has been shown that spontaneously hypertensive rats can be made normotensive by adding garlic powder to their feed (Jacob et aI., 1991). In a meta-analysis of eight clinical studies with coated garlic powder tablets, three of which specifically included hypertensive patients, four of the studies showed a significant reduction in diastolic blood pressures while three showed a significant reduction in systolic pressures (Silagy and Neil, 1994). In an observational study of some 2000 patients taking 300 mg of garlic powder three times daily, 1.3 % of the patients developed new orthostatic symptoms while on that therapy (Beck and Grunwald, 1993).  Phytotherapy of Hypertension In summary, it may be concluded that garlic powder preparations taken in an adequate dose (600- 1200 mg/day of active ingredient) have mild antihypertensive effects that are significant both therapeutically and with regard to possible side effects and drug-drug interactions (additive effects with other antihypertensives). Based on information currently available, garlic powder preparations are the only phytomedicines that can be recommended as adjuncts in the treatment of hypertensive patients. Central Nervous System Phyto-therapeutics  The plant kingdom is replete with compounds and mixtures of compounds that have a stimulating or calmative effect on the central nervous system (CNS). In cases where this action is due to a single high- potency compound that can be chemically isolated, such as morphine, cocaine, or atropine, the plant and its preparations are considered to be outside the realm of phytotherapy.  Most herbs affecting the CNS fall under the broad heading of plant sedatives. However, recent controlled therapeutic studies have identified fairly specific indications for three of the psychotropic plant drugs. 1. Ginkgo biloba extract is considered a nootropic agent that is effective in the symptomatic treatment of cognitive deficits (Hartmann and Schulz, 1991). 2. Extracts from St. John's wort have proven highly effective in the treatment of depression (Harrer, Payk, and Schulz, 1993) 3. Extracts from the kava root (Piper methysticum rhizome) have shown efficacy as anxiolytic drugs (Volz and Hansel, 1994).  psychotropic plant drugs Ginkgo biloba extract Kava root St. John's wort ‫‪Ginkgo in the Treatment of Cognitive‬‬ ‫‪Deficiency‬‬ ‫جنكو أو جنكة أو جنكو ذو‬ ‫الشقين أو جنكو ذو الفصين أو‬ ‫شجرة المعبد أو َمعبَلة أو‬ ‫الجنكو الثنائي الفلقة‬  Ginkgo Biloba Claims and effects Improved memory Reduce Alzheimer’s effects Helps hearing loss Helps calm asthma  Ginkgo Biloba Ginkgo biloba extract increases blood flow to the brain by inhibiting blood platelet aggregation and by regulating blood vessel elasticity. It has also been shown to improve blood flow through major blood vessels and capillaries.  Ginkgo biloba has no tradition as a medicinal plant in Germany. Therapeutic uses of the ginkgo seed have been described in China and other parts of eastern Asia for 2000 years. Present-day Chinese medicine uses extracts from ginkgo leaves in wound dressings. The vasoactive properties of ginkgo principles may play a role in this application. A major traditional Chinese use of ginkgo is in the treatment of bronchial asthma, presumably owing to its PAF-inhibiting properties (Schmid and Schmoll, 1994).  Botanical Description Ginkgo biloba is a dioecious plant, with male and female flowers occurring on different trees. The trees do not blossom until they are 20-30 years old. Young trees are narrow and pear-shaped, later developing a broad crown and eventually reaching a height of up to 40 m. Ginkgo trees more than 1000 years old and measuring 10-20 m in circumference have been described in China, Korea, and Japan. The last surviving member of the Ginkgoaceae family, Ginkgo biloba is unrelated to any other plant species alive today. The foliage of the ginkgo tree more closely resembles that of certain ferns than that of deciduous trees, its fan-shaped leaves lacking the central rib and cross venation seen in broad-leaf trees.  The monograph published by Commission E lists the following characteristics of medicinal ginkgo extracts 22-27% flavonoid glycosides, determined by high-performance liquid chromatography as quercetin, kaempferol, and isorhamnetin 5-7% terpene lactones, consisting of about 2.8-3.4 % ginkgolides A, B, and C and 2.6-3.2 % bilobalide less than 5 ppm ginkgolic acids. Analytic and production-related variations are included in the ranges indicated.  Other chemicals present in the extracts include hydroxykynurenic acid, shikimic acid, protocatechuic acid, vanillic acid, and p- hydroxybenzoic acid.  Pharmacology and Toxicology The 1994 Commission E monograph summarizes the experimentally documented pharmacologic actions of EGb 761 as follows: increases tolerance to hypoxia, especially in brain tissue; inhibits the development of post-traumatic or toxin-induced brain edema and hastens its resolution; reduces retinal edema and retinal lesions; inhibits the age-related decline of muscarinic choline receptors and a 2- adrenergic receptors; promotes choline uptake in the hippocampus; improves memory and learning capacity and aids in the compensation of disturbed equilibrium, acting particularly at the level of the microcirculation; improves the rheologic properties of the blood; scavenges toxic oxygen-derived free radicals; inhibits platelet activating factor (PAF) and exerts a neuroprotective effect. Trium ® Ginkgo biloba extract  The toxicity of therapeutically applied ginkgo extracts is very low. Tests in mice showed an LD50 of 7725 mg/kg on oral administration and 1100 mg/kg on intravenous administration. An acute LD50 could not be determined in rats. Tests for mutagenic, carcinogenic, and genotoxic effects were negative (Hansel et aI., 1993).  Indications, Dosages, Risks, and Contraindications Ginkgo usually has few side effects. In a few cases, people have reported stomach upset, headaches, skin reactions, and dizziness. There have been reports of internal bleeding in people who take ginkgo. It is not clear whether the bleeding was due to ginkgo or some other reason, such as a combination of ginkgo and blood- thinning drugs. Ask your doctor before taking ginkgo if patient also take blood-thinning drugs. Stop taking ginkgo 1 to 2 weeks before surgery or dental procedures due to the risk of bleeding. Always alert your doctor or dentist that patient take ginkgo. People who have epilepsy should not take ginkgo, because it might cause seizures. Pregnant and breastfeeding women should not take ginkgo. People who have diabetes should ask their doctor before taking ginkgo. DO NOT eat Ginkgo biloba fruit or seed  How to Take it Pediatric: Ginkgo should not be given to children. Adult Memory problems and Alzheimer disease: Many studies have used 120 to 240 mg daily in divided doses, standardized to contain 24 to 32% flavone glycosides (flavonoids or heterosides) and 6 to 12% triterpene lactones (terpenoids). Intermittent claudication: Studies have used 120 to 240 mg per day. It can take 4 to 6 weeks to see any effects from ginkgo. Ask your doctor to help patient find the right dose.  Possible Interactions Ginkgo may interact with prescription and non-prescription medications. If patient is taking any of the following medications, patient should not use ginkgo without talking to your doctor first. Medications broken down by the liver: Ginkgo can interact with medications that are processed through the liver. Because many medications are broken down by the liver, if patient take any prescription medications ask your doctor before taking ginkgo. Seizure medications (anticonvulsants): High doses of ginkgo could interfere with the effectiveness of anti-seizure drugs. These drugs include carbamazepine (Tegretol) and valproic acid (Depakote).  Possible Interactions Antidepressants: Taking ginkgo along with a kind of antidepressant called selective serotonin reuptake inhibitors (SSRIs) may increase the risk of serotonin syndrome, a life-threatening condition. Also, ginkgo may strengthen both the good and bad effects of antidepressants known as MAOIs, such as phenelzine (Nardil). SSRIs include: Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Fluvoxamine (Luvox) Paroxetine (Paxil) Sertraline (Zoloft) Medications for high blood pressure: Ginkgo may lower blood pressure, so taking it with blood pressure medications may cause blood pressure to drop too low. There has been a report of an interaction between ginkgo and nifedipine (Procardia), a calcium channel blocker used for blood pressure and heart rhythm problems.  Home work? What is the mechanism of action of SSRIs and what is Serotonin syndrome?  Possible Interactions Blood-thinning medications: Ginkgo may raise the risk of bleeding, especially if patient take blood-thinners, such as warfarin (Coumadin), clopidogrel (Plavix), and aspirin. Alprazolam (Xanax): Ginkgo may make Xanax less effective, and interfere with the effectiveness of other drugs taken to treat anxiety. Ibuprofen (Advil, Motrin): Like ginkgo, the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen also raises the risk of bleeding. Bleeding in the brain has been reported when using a ginkgo product and ibuprofen.  Possible Interactions Medications to lower blood sugar: Ginkgo may raise or lower insulin levels and blood sugar levels. If patient has diabetes then he should not use ginkgo without first talking to his doctor. Cylosporine: Ginkgo biloba may help protecting the cells of the body during treatment with the drug cyclosporine, which suppresses the immune system. Thiazide diuretics (water pills): There is one report of a person who took a thiazide diuretic and ginkgo developing high blood pressure. If patient takes thiazide diuretics he should ask his doctor before taking ginkgo. Trazodone: There is one report of an elderly person with Alzheimer disease going into a coma after taking ginkgo and trazodone (Desyrel), an antidepressant medication.  St.John's Wort as an Antidepressant st. John's wort (Hypericum perforatum) has a history of use as a medicine dating back to ancient Greece, where it was used for a range of illnesses, including various nervous disorders. St. John's wort also has antibacterial, antioxidant, and antiviral properties. Because of its anti-inflammatory properties, it has been applied to the skin to help heal wounds and burns. St. John's wort is one of the most commonly purchased herbal products in the United States.  ‫‪St.John's Wort as an Antidepressant‬‬ ‫العرن المثقوب أو نبتة سانت‬ ‫‪The plant gets its‬‬ ‫جونز ‪St John's wort‬أو‬ ‫‪name because it is‬‬ ‫نبتة سيدي يحيى وتعرف في‬ ‫‪often in full bloom‬‬ ‫بالد الشام باسم عشبة العرن أو‬ ‫‪around June 24,‬‬ ‫كما تسميها بعض المراجع‬ ‫‪the day‬‬ ‫الحديثة باسم عشبة القلب‪ ،‬هي‬ ‫‪traditionally‬‬ ‫نبتة صفراء تعيش في بعض‬ ‫‪celebrated as the‬‬ ‫مناطق أميركا الشمالية وأوروبا‬ ‫‪birthday of John‬‬ ‫وآسيا وروسيا والهند والصين‪.‬‬ ‫‪the Baptist. Both‬‬ ‫وتُعد مفيدة لعالج الكآبة‪.‬المواد‬ ‫‪the flowers and‬‬ ‫الفعالة فيها تحتوي على‬ ‫‪leaves are used as‬‬ ‫هيبريسين‪ ،‬وكانت تستخدم منذ‬ ‫‪medicine.‬‬ ‫العصور الوسطى كعشبة‬ ‫لألسترخاء‪.‬‬ Fam. Hypericaceae Perennial plant Flower: bright yellow oval shaped leaves with black dots Native to Northern Africa, Europe and Western Asia. Hypericum perforatum  Depression Evidence -Depression – widely prescribed in Europe for depression – Commission E “approved” for this use Commission E- psychological disturbances, depression, anxiety, nervous unrest; topically the oil for bruises, myalgia, burns Other Uses: less well documented – Hypericin antiviral studies – SJW long used to heal wounds – Plant oil has antimicrobial activity  Pharmacokinetics Metabolized by cytochrome P450 in the liver (like many drugs) Hypericin may not cross the blood-brain barrier, hyperforin more likely an active ingredient Most of the purported active ingredients are heterocyclic and are metabolized quickly (half life < 6 hrs).  Dosage Dosage depends on the hypericin content Usually advised that the St. John’s wort extract be standardized to contain 0.3% hypericin at a dosage of 300mg, three times a day Takes about 6 weeks to notice a difference Generally takes longer to reach full effectiveness than prescription antidepressants Standardized extract containing about 0.3% hypericin or 2-3% hyperforin; 300mg TID for treatment.  Forms of Hypericum Capsules Teas Tablets Tinctures Oil-based skin lotions (not to be ingested) Chopped/powered  Cautions Should not be used during pregnancy or while breast feeding as there is no information on it's safety under these conditions Should not be used for severe depression or bipolar disorder as not enough research is yet available to show effectiveness in these circumstances Do not take St. John’s Wort in combination with MAOI’s – Can produce a dangerous rise in blood pressure Should not be taken in combination with prescription SSRI’s as this can lead to serotonin syndrome – too much serotonin.  Adverse effects –Photosensitivity-animals –Photosensitivity- humans- in high doses is a risk  St.John's Wort as an Antidepressant In recent years, St. John’s wort has been studied extensively as a treatment for depression. Most studies show that St. John's wort may help treat mild-to-moderate depression, and has fewer side effects than most other prescription antidepressants. But it interacts with a number of medications, so it should be taken only under the guidance of a health care provider.  St.John's Wort as an Antidepressant Don't use herbs to treat severe depression -- where patient that have trouble functioning day to day, or have thoughts of harming yourself or others. Always refer to a doctor if the patient’s depression is making it hard for him to function  Key Constituents, Analysis, Pharmacokinetics Rubbing a bud or flower from the St. John's wort between the fingers immediately produces a purple stain caused by characteristic constituents of the plant - hypericin, pseudohypericin, protohypericin, protopseudohypericin, and cyclopseudohypericin, all belonging to the group of naphthodianthrones. The dried plant parts contain an average of about 0.1 % of these compounds; standardized extracts may contain several times that amount.  Chemistry Hypericin is a fluorescent red pigment classified as a dianthrone. Hyperforin is derived from phloroglucinol, substituted with several lipophilic isoprene chains.  OH O OH HO CH3 HO CH3 OH O OH hypericin  Hyperforin vs. Hypericin Scientists used to think the active constituent in St. John’s Wort (SJW) was only due to Hypericin and its inhibitory effects on the monoamine oxidase enzymes. However, recent studies have shown that SJW may owe its main effects on depression through Hyperforin. It is able to pass through the blood-brain barrier and may inhibit the action of the enzyme dopamine ß-hydroxylase, which is required in converting dopamine to norepinephrine. As a result of this enzyme inhibition, this may lead to increased dopamine levels - thus possibly decreasing norepinephrine and epinephrine.  Depression There is good evidence that St. John's wort may reduce symptoms in people with mild-to-moderate, but not severe (or major) depression. In many studies it seems to work as well as selective serotonin reuptake inhibitors (SSRIs), a popular type of antidepressant often prescribed to treat depression. SSRIs include fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft). In addition, St. John's wort doesn't seem to cause loss of sex drive, one of the most common side effects of antidepressants.  Other Uses St. John's wort has also shown promise in treating the following conditions, a few of which are related to depression. Premenstrual syndrome (PMS): Research suggests that St. John's wort may help relieve physical and emotional symptoms of PMS in some women, including cramps, irritability, food cravings, and breast tenderness. One study reported a 50% reduction in symptom severity. Menopause: There's some evidence to suggest that St. John's wort, combined with black cohosh, helps improve mood and anxiety during menopause. Seasonal affective disorder (SAD): Used alone, St. John's wort has improved mood in people with SAD, a type of depression that occurs during the winter months because of lack of sunlight. SAD is usually treated with light therapy. Research shows that using St. John's wort together with phototherapy works even better.  Other Uses Eczema, wounds, minor burns, hemorrhoids: St. John's wort has antibacterial properties and may also help fight inflammation. Applied topically (to the skin), it may relieve symptoms associated with minor wounds and skin irritation. Obsessive compulsive disorder (OCD), social phobia: One early open-label study found that taking St. John's wort 450 mg, 2 times a day for 12 weeks improved OCD symptoms. However, other studies show that St. John's wort doesn’t improve OCD.  Available Forms St. John's wort can be obtained in many forms: capsules, tablets, tinctures, teas, and oil-based skin lotions. Chopped or powdered forms of the dried herb are also available. Most products are standardized to contain 0.3% hypericin.  How to Take It Pediatric Most studies on St. John's wort have been conducted in adults. However, one study (more than 100 children under age 12) indicated that St. John's wort may be a safe and effective way of treating mild-to-moderate symptoms of depression in children. Never give your child St. John's wort without medical supervision. Children who are being treated with St. John's wort should be carefully monitored for side effects, such as allergic reactions or upset stomach. Patient should not try to treat depression in a child without a doctor's help because depression can be a serious illness. Adult Dry herb (in capsules or tablets): The usual dose for mild depression and mood disorders is 300 mg (standardized to 0.3% hypericin extract), 3 times per day, with meals. St. John's wort is available in time-release capsules. St. John's wort is also available as a liquid extract or tea. Ask your doctor to help patient find the right dose. It may take 3 to 6 weeks to feel any effects from St. John's wort. Don't stop taking St. John’s wort all at once because that may cause unpleasant side effects. Gradually lower the dose before stopping.  Precautions St. John's wort is often used to treat depression. If your depression is causing problems with your daily life, or patients are having thoughts of suicide or of harming yourself or others, patient need to see a doctor immediately. St. John's wort should not be used to treat severe depression.  Precautions Side effects from St. John's wort are generally mild and include stomach upset, hives or other skin rashes, fatigue, restlessness, headache, dry mouth, and feelings of dizziness or mental confusion. St. John's wort can also make the skin overly sensitive to sunlight, called photodermatitis. If patient have light skin and are taking St. John's wort, wear long sleeves and a hat when in the sun, and use a sunscreen with at least SPF 15 or higher. Avoid sunlamps, tanning booths, and tanning beds.  Precautions St. John's wort are that it may interfere with getting pregnant or make infertility worse it may make symptoms of ADD and ADHD worse, especially among people taking methylphenidate; that it may increase the risk of psychosis in people with schizophrenia; and that it may contribute to dementia in people with Alzheimer disease. St. John's wort can interact with medications used during surgery, patient should stop taking it at least 5 days or more before surgery. Women who are pregnant, trying to become pregnant, or breastfeeding should not take St. John's wort.  Possible Interactions Antidepressants -- St. John's wort may interact with medications used to treat depression or other mood disorders, including tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors (MAOIs). Taking St. John's wort with these medications tends to increase side effects, and could lead to a dangerous condition called serotonin syndrome. Do not take St. John's wort with other antidepressants, including: SSRIs: Citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), paroxetine (Paxil), fluoxetine (Prozac), sertraline (Zoloft) Tricyclics: Amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil) MAOIs: Phenelzine, (Nardil), tranylcypromine (Parnate) Nefazodone (Serzone) Allergy drugs (antihistamines) -- St. John's wort may reduce levels of these drugs in the body, making them less effective: Loratadine (Claritin) Cetirizine (Zyrtec) Fexofenadine (Allegra) Clopidogrel (Plavix) -- Theoretically, taking St. John's wort along with clopidogrel may increase the risk of bleeding. Dextromethorphan (cough medicine) -- Taking St. John's wort at the same time as dextromethorphan, a cough suppressant found in many over-the-counter cough and cold medicines, can increase the risk of side effects, including serotonin syndrome.  Possible Interactions Digoxin -- St. John's wort may lower levels of the medication and make it less effective. Do not take St. John's wort if patient take digoxin. Drugs that suppress the immune system -- St. John's wort can reduce the effectiveness of these medications, which are taken after organ transplant, or to control autoimmune diseases. There have been many reports of cyclosporin blood levels dropping in those with a heart or kidney transplant, even leading to rejection of the transplanted organ. Adalimumab (Humira) Azathioprine (Imuran) Cyclosporine Etanercept (Enbrel) Methotrexate Mycophenolate mofetil (CellCept) Tacrolimus (Prograf)  Drugs to fight HIV -- The Food and Drug Administration recommends that St. John's wort not be used with any type of antiretroviral medication used to treat HIV or AIDS. Birth control pills -- There have been reports of breakthrough bleeding in women on birth control pills who were also taking St. John's wort. It is possible that the herb might make birth control pills less effective, leading to unplanned pregnancies. Aminolevulinic acid -- This medication makes your skin more sensitive to sunlight. St. John's wort also increases skin sensitivity to light. Together, they may have a dangerous impact on skin sensitivity to the sun. Reserpine -- Based on animal studies, St. John's wort may interfere with reserpine's ability to treat high blood pressure.  Sedatives -- St. John's wort can increase the effect of drugs that have a sedating effect, including: Anticonvulsants, such as phenytoin (Dilantin) and valproic acid (Depakote) Barbiturates Benzodiazepines, such as diazepam (Valium) Drugs to treat insomnia, such as zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta), and ramelteon (Rozerem) Tricyclic antidepressants, such as amitriptyline (Elavil) Alcohol Alprazolam (Xanax) -- St. John's wort may speed up the breakdown of Xanax in the body, making it less effective.  Theophylline -- St. John's wort can lower levels of this medication in the blood. Theophylline is used to open the airways in people with asthma, emphysema, or chronic bronchitis. Triptans (used to treat migraines) -- St. John's wort can increase the risk of side effects, including serotonin syndrome, when taken with these medications: Naratriptan (Amerge) Rizatriptan (Maxalt) Sumatriptan (Imitrex) Zolmitriptan (Zomig) Warfarin (Coumadin) -- St. John's wort reduces the effectiveness of warfarin, an anticoagulant (blood thinner).  Other drugs -- Because St. John's wort is broken down by certain liver enzymes, it may interact with other drugs that are broken down by the same enzymes. Those drugs may include: Antifungal drugs, such as ketoconazole (Nizoral), itraconazole (Sporanox), fluconazole (Diflucan) Statins (drugs taken to lower cholesterol), including atorvastatin (Lipitor), lovastatin (Mevacor), and simvastatin (Zocor) Imatinib (Gleevac) -- may make Gleevac less effective Irinotecan (Camptosar) -- may speed up the rate at which Camptosar is broken down by the body, making it less effective Some calcium channel blockers (taken to lower blood pressure) Any medication broken down by the liver  St. John’s Wort Drug Interactions Increases Decreases Potency of: Potency of: SSRIs HIV medications Triptans TCAs Barbiturates Cyclosporine Alcohol Estrogen Narcotics Digoxin Fenfluramine Theophylline Warfarin  Kava as an Anxiolytic Kava kava (Piper methysticum) has been used as a ceremonial drink in the Pacific Islands for hundreds of years. Some people report its effects are similar to alcohol. The roots are chewed or ground into a pulp and added to cold water. The resulting thick brew, which has been compared to the social equivalent of wine in France, is offered to guests and dignitaries visiting the Pacific Islands. In addition to its ceremonial uses, kava is best known for its relaxing qualities. Kava is said to elevate mood, well being, and contentment, and produce a feeling of relaxation. Several studies have found that kava may be useful in the treatment of anxiety, insomnia, and related nervous disorders.  However, there is serious concern that kava may cause liver damage. More than 30 cases of liver damage have been reported in Europe. However, researchers have not been able to confirm that kava is toxic to the liver. Some countries have taken kava off the market. It remains available in the United States. But the Food and Drug Administration (FDA) issued a consumer advisory in March 2002 regarding the "rare" but potential risk of liver failure associated with kava-containing products.  Uses of Kava Evidence suggests kava may be helpful for the following health problems Anxiety A number of clinical studies, though not all, have found kava to be effective in treating symptoms associated with anxiety. According to one study, kava and diazepam (Valium) cause similar changes in brain wave activity, suggesting they may work in the same ways to calm the mind. Research on using kava for anxiety has decreased because of reports of liver toxicity. A 2004 study found that 300 mg of kava may improve mood and cognitive performance. That is significant because some prescription drugs used to treat anxiety, such as benzodiazepines (like Valium and alprazolam or Xanax), tend to decrease cognitive function. Insomnia Preliminary evidence suggests that kava may help improve sleep quality and decrease the amount of time needed to fall asleep. Due to concerns about kava's safety and the fact that other herbs can treat sleeplessness, kava is not the best choice for treating insomnia.  Possible Interaction Kava should not be given unless under the supervision of a doctor. Kava should not be given with prescription or over-the-counter medications. Kava may interact with the following: Anticonvulsants -- Kava may increase the effects of medications, such as phenytoin (Dilantin), that are used to treat seizures. Alcohol -- Do not use kava and alcohol together. The risk of impairment and the risk of liver damage are greatly increased. Anti-anxiety agents -- Kava may increase the effects of CNS depressants such as benzodiazepines, used for sleep disturbances or anxiety (particularly alprazolam or Xanax), and barbiturates (such as pentobarbital), which are used for sleep disorders and seizures. Benzodiazepines include: Alprazolam (Xanax) Diazepam (Valium) Lorazepam (Ativan) Triazolam (Halcion) Chlordiazepoxide (Librium)  Restlessness and Sleep Disturbances States of nervous unrest and sleep disturbances are considered traditional indications for the use of preparations made from valerian, hops, lemon balm, and passion flower. These are gentle herbs that do not produce strong sedative or hypnotic effects. It is true that several constituents have been isolated that appear to have sedative effects in some experimental settings, such as valepotriates and valerenic acids isolated from valerian. But the final concentrations of these compounds in medicinal products are so low that they could hardly account for any sedative or tranquilizing effects in human patients.  Valerian Valerian is somewhat unique in that its actions and efficacy have been better documented (for selected valerian extracts) than for the other three herbs mentioned before. Moreover, valerian is a widely known herb both in Germany and abroad, so a separate section will be devoted to its discussion  Valerian The medicinal valerian used at our latitudes (Valeriana officinalis, is but one of approximately 250 valerian species that occur worldwide. Native to Europe and the temperate zones of Asia, it is an erect perennial that reaches a height of about 50-150 cm. It prefers damp, swampy areas and blooms from June to August, developing tiny white to pink flowers that grow in terminal cymes. Valerian for medicinal use is cultivated and harvested from September to October. Valerian Cymes  Valerian has been used to ease insomnia, anxiety, and nervous restlessness since the second century A.D. It has also been suggested to treat stomach cramps. Germany's Commission E approved valerian as an effective mild sedative and the United States Food and Drug Administration listed valerian as "Generally Recognized As Safe" (GRAS). Scientists aren't sure how valerian works, but they believe it increases the amount of a chemical called gamma aminobutyric acid (GABA) in the brain. GABA helps regulate nerve cells and has a calming effect on anxiety. Drugs such as alprazolam (Xanax) and diazepam (Valium) also work by increasing the amount of GABA in the brain. Researchers think valerian may have a similar, but weaker effect  Insomnia Valerian is a popular alternative to prescription medications for sleep problems because it is considered to be both safe and gentle. Some studies show that it helps people fall asleep faster and feel that they have a better quality of sleep. Unlike many prescription sleeping pills, valerian may have fewer side effects, such as morning drowsiness. Valerian is often combined with other sedating herbs, such as hops (Humulus lupulus) and lemon balm (Melissa officianalis), to treat insomnia. In one study of postmenopausal women, a combination of valerian and lemon balm helped reduce symptoms of insomnia  What's It Made Of? The root of the plant is used as medicine and is pressed into fresh juice or freeze-dried to form powder. Available Forms Valerian fluid extracts and tinctures are sold in alcohol or alcohol-free (glycerite) bases. Powdered valerian is available in capsule and tablet form, and as a tea. Valerian root has a sharp odor. It is often combined with other calming herbs, including passion flower (Passiflora incarnata), hops (Humulus lupulus), lemon balm (Melissa officinalis), skullcap (Scutellaria lateriflora), and kava (Piper methysticum) to mask the scent. However, kava has been associated with liver damage, so avoid it.  How to Take It Valerian is often standardized to contain 0.3 to 0.8% valerenic or valeric acid, although researchers aren't sure that these are the active ingredients. Pediatric Don't give valerian to a child without first talking to your doctor. Adult For insomnia, valerian may be taken 1 to 2 hours before bedtime, or up to 3 times in the course of the day, with the last dose near bedtime. It may take a few weeks before the effects are felt. Tea: Pour 1 cup boiling water over 1 teaspoonful (2 to 3 g) of dried root, steep 5 to 10 minutes. Tincture (1:5): 1 to 1 1/2 tsp (4 to 6 mL) Fluid extract (1:1): 1/2 to 1 tsp (1 to 2 mL) Dry powdered extract (4:1): 250 to 600 mg For anxiety, 120 to 200 mg, 3 to 4 times per day Once sleep improves, keep taking valerian for 2 to 6 weeks.  Possible Interactions Valarian should not be used without talking to your health care provider. Medications broken down by the liver -- Valerian may slow down how quickly certain drugs are broken down by the liver. Many medications rely on the liver to break them down, so it's possible that in some cases, too much of these drugs could build up in the body. To be safe, ask your doctor before taking valerian if you are also taking any other medications. Sedatives -- Valerian can increase the effect of drugs, including: Anticonvulsants, such as phenytoin (Dilantin) and valproic acid (Depakote) Barbiturates Benzodiazepines, such as alprazolam (Xanax) and diazepam (Valium) Drugs to treat insomnia, such as zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta), and ramelteon (Rozerem) Tricyclic antidepressants, such as amitriptyline (Elavil) Alcohol The same is true of other herbs with a sedating effect, such as chamomile, lemon balm, and catnip.  Possible Interactions Other drugs -- Because valerian is broken down by certain liver enzymes, it may interact with other drugs that are broken down by the same enzymes. These may include many different medications, including but not limited to the following: Antihistamines Statins, taken for high cholesterol Some antifungal drugs Anesthesia -- Valerian may increase the effects of anesthesia. If you are having surgery, it is important to tell your doctors, especially your surgeon and anesthesiologist, that you are taking valerian. The doctors may recommend you slowly lower the dose of valerian before surgery. Or, they may allow you to use valerian up to the time of surgery, making any needed adjustments to the anesthesia.  Hops, Lemon Balm, Passion Flower, and Lavender Monographs published by Commission E cite restlessness and sleep disturbances as the indications for treatment with hop strobiles, lemon balm leaves, passion flower, and lavender flowers  Lavender (Lavendula angustifolia). Hops (Humulus lupulus).  Hop Strobiles and Hop Glands ‫الجنجل الشائع أو حشيشة الدينار‬ While hops have been used in traditional European medicine as a tonic, diuretic, and aromatic bitter, the use of hops as a calmative is a more recent development. The fatigue and sleep-promoting effects of hops were discovered when it was noticed that hop pickers tired easily, apparently due to the transfer of hop resin from their hands to their mouths (Tyler, 1987).  Hop Strobiles and Hop Glands Hop strobiles are the female flowers of the cultivated hop plant (Humulus lupulus). They contain bitter principles including humulone and lupulone. These principles combine to form hop resin which occurs in 15-30 % concentration in the strobiles and 50-80 % in the hop glands (lupulin). The strobiles also contain up to 1 % volatile oil and up to 4 % tannins. Only the fresh dried herb contains these substances in full concentration.  There is no toxicologic risk associated with hops. The LD50 for orally administered hop extract or lupulones in mice is in the range of 500-3500 mg/kg (Hiinsel et al., 1993). The Commission E monograph of December 5, 1984, cites "discomfort due to restlessless or anxiety and sleep disturbances" as the indications for hops. The recommended dose is 0.5g of the dried herb, or its equivalent in extract-based products, taken one to several times daily.  Botany Hop or hops (Humulus lupulus) is a climbing vine belonging to the genus Humulus in the family Cannabaceae. The genus name Humulus has its origin in the Slavic term for hops, chmele, which was later Latinized. The species name lupulus is a diminutive derived from lupus, the Latin word for wolf, based on the plant’s habit of climbing on other plants as a wolf does a sheep. Its common name is derived from the Anglo-Saxon hoppan (to climb). In Europe, hops is cultivated in Germany, Great Britain, Poland, and the Czech Republic. In Asia, cultivation takes place in certain areas of China and to a limited extent in Japan.  Part Used Hops are the female flowers (also called seed cones or strobiles) of the hop plant.  Historic Uses The historic use of hops is interesting as its technical properties—as flavor and for the preservation of beer—were discovered in the mid ages, but reports of its medicinal use from that time were not very encouraging. Its bitterness fends off decomposition of beverages and increases shelf life.” With these antimicrobial properties and its ideal flavor, in the region of Germany from the 11th century on, hops replaced all other substances that were formerly used to attempt to improve the taste and increase the storage time of beer.  Chemistry Fresh lupulin consists of various compounds, mainly bitter acids, volatile oils, and polyphenols. The aromatic odor of the hops strobiles is due to a volatile oil, present in a yield of about 0.3-1.0%. Active compounds thought to be responsible for its medicinal effects include 15-30% resins (such as humulon, lupulon, and its derivatives 2- methyl-3-butenol), tannins, and flavonoids, as well as essential oils (with its main constituents myrcene, alpha-humulene and beta- caryophyllene, and farnesene).  Lupulin Lupulin, the fine yellow resinous substance of the female flowers from hops.  Alpha Acids Alpha acids are the most commonly referred to acids when it comes to hops, as these are where the hops get most of their bittering effect from. There are five main alpha acids, and they are: Humulone -Cohumulone Adhumulone Posthumulone Prehumulone Basically, humulone is a soft bitterness, cohumulone is a harsh bitterness, and the rest are kind of a mystery. When looking for a hop high in alpha acids, the general rule is high humulone and low cohumulone.  Beta Acids The second type of acid found in hops are beta acids. If hops were a band, alpha acids would be the lead singer, and beta acids would be the 4th guitarist. Most people don’t really know what he does, but what he plays is still important to the song. Beta acids are comprised of three main types. They are: Lupulone Colupulone Adlupulone  Alpha and beta acids Alpha acids are generally the bitterness you taste in a beer, and they dissolve into solution immediately. They still take some time to release their bitterness, which is why timing of their addition to the boil is vital. The alpha acids isomerize in the boil to form isomerized alpha acids. Beta acids take longer to break down and show up best in aged beers. Noble hops have the closest 1:1 ratio of alpha to beta hops, where most other hops have about a 2:1 ratio.  Uses Hops has been consistently employed in combination products with other sleep- promoting herbal preparations. In amounts of 0.3 g and up to 1 g several times a day, lupulin was used against incontinence, to reduce sexual desire (anaphrodisiac), and to treat excessive irritability or sensibility to stimulation of the sexual organs (erethismus genitalis), to treat sleeplessness, and to work against nervousness, migraine headache, and sluggish digestion.  Hops “Bitters” for Digestive Complaints The British Herbal Pharmacopoeia notes the use of hops as a “bitter,” while the monograph from WHO provides details associated with this action, i.e., treatment of dyspepsia and lack of appetite. In Japan, hops is used for activation of gastric function. However, there are actually few reports about the effect of hops on gastric function. In North America, Belgium, and England, hops has been used to aromatize liquors, which serve well as aperitifs and digestifs due to their reputation for increasing appetite as well as digestion.  Estrogenic Activity Associated with Hops Circumstantial evidence over many years, including menstrual disturbances reported to be common among female hops-pickers, linked hops with potential estrogenic effect. The estrogenic principle in hops ext