phytoterapy and chem. of Nat.Produts Lectures Copy.pdf

PHARMACOLOGICAL ACTIVITIES OF NATURAL PRODUCTS Phytotherapy and chem. of natural products Dr. Khaled Tawaha Protists are simple eukaryotic organisms that are neither plants nor animals or fungi.... The term 'Protista' is derived from the Gre...

PHARMACOLOGICAL ACTIVITIES OF NATURAL PRODUCTS Phytotherapy and chem. of natural products Dr. Khaled Tawaha Protists are simple eukaryotic organisms that are neither plants nor animals or fungi.... The term 'Protista' is derived from the Greek word “protistos”, meaning “the very first“. These organisms are usually unicellular and the cell of these organisms contains a nucleus which is bound to the organelles 1- DRUGS ACTING ON THE NERVOUS SYSTEM 2-THE HEART, CIRCULATION AND BLOOD 3- ACTION ON THE Gastrointestinal TRACT 4-THE NASAL AND RESPIRATORY SYSTEM 6-THE LIVER 7-THE URINARY AND REPRODUCTIVE SYSTEMS 8-THE SKIN AND MUCOUS MEMBRANES 9-ACTION ON SUGAR METABOLISM 10- STEROIDS AND ANTI-INFLAMMATORY DRUGS 11- NONSTEROIDAL ANTI-INFLAMMATORY DRUGS 12-TREATMENT OF INFECTIONS 13- TREATMENT OF MALIGNANT DISEASES 14- TREATMENT OF ALLERGIES 15-THE IMMUNE SYSTEM 16-VITAMINS Phytotherapy and chem. of natural products Dr. Khaled Tawaha A valid scheme for the study of medicinal plants and their products, and one which emphasizes pharmaceutical use, can be based on pharmacological action. The scheme can be extended to include numerous plants which, although eliciting a pharmacological response, are not, for varied reasons, used as drugs. In the latter category would be placed hundreds of alkaloid- and glycoside-containing plants. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Some major pharmacological groupings involve drugs which act on the nervous systems, heart and blood vessels, lungs, gastrointestinal tract, kidneys, liver, reproductive organs, skin and mucous membranes. Other categories include hormones, vitamins and chemotherapeutic. Phytotherapy and chem. of natural products Dr. Khaled Tawaha A system based on clinical usage may be more straightforward for the thoroughly-studied allopathic drugs used in Western medicine but difficulties can arise for plants used in traditional medicine because of the often numerous conditions for which any one drug may be employed. Phytotherapy and chem. of natural products Dr. Khaled Tawaha DRUGS ACTING ON THE NERVOUS SYSTEM Phytotherapy and chem. of natural products Dr. Khaled Tawaha Introduction The nervous system coordinates and regulates the various voluntary and involuntary activities of the body and is conveniently considered under two headings-the central nervous system (CNS) and the autonomic nervous system. The two are interlinked and some drugs which affect the CNS may also produce reactions associated with the autonomic system. In the case of others which act via the autonomic system it is sometimes more convenient to classify them under other headings appropriate to the organs involved; thus, those producing vasoconstriction or vasodilation may appear under the consideration of the circulatory and respiratory systems. Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE CENTRAL NERVOUS SYSTEM The central nervous system comprises the brain (cerebrum, cerebellum, medulla oblongata) and the spinal cord. It coordinates the voluntary activities of the body and exhibits numerous interactions within the system together with linkages to the autonomic system. Drugs involved with the CNS can be broadly classified according to whether they have a general stimulatory or depressant action → with further subdivision regarding specific actions such as→ anticonvulsant and psychopharmacological activities. Some of the most useful natural drugs of the group are the→ narcotic (opioid) analgesic others→ such as the hallucinogenic drugs have important sociological implications. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Drugs acting on the central nervous system →Drugs affecting mental activity 1-Mescaline: Hallucinogenic. Obtained from peyote cactus. 2-Cannabis: Hallucinogenic. Active constituents contained in the resin of Cannabis sativa ‫ﻗﻨﺐ‬/‫ﻗﻨﺐ ھﻨﺪي‬ (THC,CBD)→ look for ( home work) 3-Purine bases:(e.g. caffeine, theophylline, theobromine)Stimulate mental activity; constituents of beverages-coffee(Coffea arabica)‫ﻗﮭﻮة‬, tea(Camellia sinensis)‫اﻟﺸﺎي‬, kola (cola acuminate), mate(llex paraguariensis)‫اﻟﻤﺘﺔ‬. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 4-Cocaine: One of the earliest drugs used as a mental stimulant. Produces addiction. Contained in the leaves of Erythroxylum coca 5- Ginkgo (Ginkgo biloba) :Improves short term memory. 6- Ginseng (Panax ginseng): Improves mental concentration particularly in the elderly. 7- Galanthamine: Promising Amaryllidaceous alkaloid for treatment of Alzheimer's disease. 8- Hypericum (Hypericum perforatum): Popular herbal remedy for relief of mild- moderate depression. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 9-Sage (Salvia officinalis): Revived‫ اﻧﻌﺸﺖ‬interest in its use for counteracting memory loss. 10-Reserpine: Depresses mental activity. Used in psychiatric treatment.Obtained from Rauwolfia spp.(e.g: Rauwolfia serpentina). 11-Yohimbine: Similar action to reserpine but its antiadrenaline reactions and effect on heart muscle render it of no clinical use. Found in various species of the Apocynaceae. 12-Valerian :(Valeriana officinalis), Passiflora (Passiflora incarnate): Sedative and hypnotic; aid sleeplessness and improve sleep quality.(Hops,Melissa) 13- Lysergic acid diethylamide:Hallucinogenic. Prepared by partial synthesis from ergot(Claviceps purpurea)‫ ﺻﺪى اﻟﻘﻤﺢ‬alkaloids or by artificial culture. Phytotherapy and chem. of natural products Dr. Khaled Tawaha → Analeptic drugs (stimulants of the CNS in addition to the mental stimulantsindicated above) 1- Picrotoxin: Analeptic previously used in the treatment of barbiturate poisoning. Obtained from berries of (Anamirta cocculus) 2- Strychnine: Weak analeptic; toxic doses produce spinal convulsions. Obtained from the seeds of(Strychnos nux vomica). Phytotherapy and chem. of natural products Dr. Khaled Tawaha →Central depressants of motor function Tropane alkaloids (e.g. hyoscine= scopolamine, Hyoscyamine, atropine= D and L hyoscyamine): Formerly the only drugs effective in the alleviation of the symptoms of Parkinson's disease. Used in treatment of travel sickness and delirium tremens. 1- Datura (Datura stramonium). 2 -Belladonna or deadly nightshade (Atropa belladonna). 3-Henbane (Hyoscymus niger). Phytotherapy and chem. of natural products Dr. Khaled Tawaha →Analgesic drugs 1-Morphine(from opium poppy ‫(ﺧﺸﺨﺎش ﻣﻨﻮم‬Papaver somniferum)): Effective for relief of severe pain. Depressant action on the cough and respiratory centers. The principal alkaloid of opium. 2-Codeine(from opium poppy): Although less active than morphine it is a much safer drug for the relief of mild pain and for use as a cough suppressant‫ز‬ Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE AUTONOMIC NERVOUS SYSTEM The autonomic nervous system supplies the smooth muscle tissues and glands of the body. Its function is complex, involving ganglia situated outside the spinal cord; it is composed of two divisions: 1- The sympathetic (thoracolumbar or adrenergic) division, which arises from the thoracic and lumbar regions. 2-The parasympathetic (craniosacral or cholinergic) division, originating in the brain and in the sacral region. In general, an increase in activity of the sympathetic system gears the body for immediate action (fight and flight), whereas stimulation of the parasympathetic or vagal system produces effects more associated with those occurring during sleep and with energy conservation. Two important neurotransmitter substances of the autonomic nervous system are 1-acytelcholine 2- noradrenalin and its derivatives. Phytotherapy and chem. of natural products Dr. Khaled Tawaha  Drugs acting on the autonomic nervous system. Acetylcholine-like drugs 1- Pilocarpine: → from leaves of Pilocarpus microphyllus ‫ﺟﺎﺑﻮرﻧﺎري‬ ------>to treat narrow and wide angle glaucoma. (By lowering of intraocular pressure of both). 2- Arecoline: →from seeds of Areca catechu 3- Muscarine→ from Amanita spp. And other fungi 4- Physostigmine (a cholinesterase inhibitor)→from seeds of Physostigma venenosum (Calabar bean ‫)ﻟﻮﺑﯿﺎ ﻛﺎﻻﺑﺎر‬ ------>To treat glaucoma but pilocarpine is more effective. Phytotherapy and chem. of natural products Dr. Khaled Tawaha →2- Antagonists of acetylcholine 1-Tropane ester alkaloids (e.g. hyoscine, atropine) →From a number of Solanaceae (e.g. Duboisia, Atropa, Datura etc.) They have widespread uses involving their gastrointestinal, bronchial, genito-urinary and ophthalmic effects in addition to the CNS activity. →3- Neuromuscular blocking agents (e.g. tubocurarine) Ganglion blocking agents (e.g. tubocurarine in large doses) (not clinically important)→ From leaves and stems of Chondodrendon tomentosum Phytotherapy and chem. of natural products Dr. Khaled Tawaha →4-Adrenaline-like drugs 1- Ephedrine: From stems of Ephedra spp.; mainly synthetic(use ?!). →5-Antagonists of adrenaline 1-Ergot alkaloids (e.g. ergotamine from From sclerotia of Claviceps spp.). 6-Noradrenaline depletion 1- Reserpine (from Rauwolfia serpintina):has antihypertensive effect resulting from dilation of heart and circulatory vessels. 7-Ophthalmic preparations The eye, being under the control of the autonomic nervous system, is affected by some of the drugs mentioned above; these include atropine, hyoscine, physostigmine and pilocarpine. Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE HEART,CIRCULATION AND BLOOD Many factors affect the complex regulation of the heart and the large group of drugs which is known to possess cardiovascular activity is not confined ‫ﻳﻘﺘﺼﺮ‬ ‫ ﻣﻘﯿﺪة‬to act on the heart muscle itself. Thus those drugs possessing anti arrhythmic, antihypertensive, antihyperlipidemic, vasoconstrictor, vasodilator, blood anticoagulant, and platelet aggregation activities must also be considered in this group Phytotherapy and chem. of natural products Dr. Khaled Tawaha 1-Cardioactive glycosides : many plant genera containing cardioactive glycosides (Digitalis ‫أﺻﺎﺑﻊ‬ ‫اﻟﻌﺬراء‬, Strophanthus , Convallaria, Nerium and Thevetia) 2- Anti arrhythmic drugs The cardiac glycosides can be used to control supraventricular (arterial) cardiac arrhythmias. There are a number of other drugs such as the alkaloid quinidine (obtained from various cinchona barks; C. succirubra) which act on both supraventricular and ventricular arrhythmias. →Its therapeutic use for the attempted conversion of arterial fibrillation to sinus rhythm has now been largely replaced by electrical cardio version. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 3- Antihypertensive drugs The control of hypertension is an important element in the management of cardiovascular disorders. → Of the hypotensive plant drugs rauwolfia and its principal alkaloid reserpine. Other plants regularly employed by Western herbal practitioners include mistletoe, Crataegus, Yarrow, Tilia and Fagopyrum. 4- Platelet ‫ ﺻﻔﺎﺋﺢ‬activating factor (PAF) antagonists In the circulatory system thrombi may be caused on the arterial side as a result of the adhesion of blood platelets to one another and to the walls of the vessels. This platelet aggregation is triggered‫ ﻳﺤﻔﺰ‬by the platelet activating factor which is released from activated basophils. PAF from the rabbit was characterized in the 1970s as a I-O-alkyl-2acetyl-sn- glyceryl-3-phosphoryIcholine. A number of prostaglandins and thromboxanes are also involved in the aggregation mechanism and thromboxane A2 which is synthesized from arachidonic acid is particularly potent. In undamaged vessels thromboxane A2 is balanced by a prostaglandin e.g. prostacyclin of the arterial intima which has deaggregation properties. Phytotherapy and chem. of natural products Dr. Khaled Tawaha → For the secondary prevention‫ وﻗﺎﻳﺔ‬of cerebrovascular or cardiovascular disease, aspirin, which irreversibly acetylates the platelet enzyme cyclo-oxygenase has been employed at dosages of 300 mg (80mg) daily with useful results. A large number of plants have been screened for anti-PAF activity. One of the first natural products so identified was the neolignan kadsurenone obtained from Piper futokadsura, a plant long used in Chinese traditional medicine for allergy treatments. Phytotherapy and chem. of natural products Dr. Khaled Tawaha  How does aspirin act as an anti clotting agent?  Anticoagulants such as heparin or warfarin (also called Coumadin) slow down your body's process of making clots.  Antiplatelet drugs, such as aspirin, prevent blood cells called platelets from clumping together to form a clot. → Other plants of traditional medicine reported to have anti-PAF activity include species of Forsythia, Arctium, Centipeda, Tussilago, Pyrola, Populus and Peucedanum. The active constituents include lignans, sesquiterpenes, coumarins, pyrocatechol and salicyl alcohol. → Extracts of the maidenhair tree, Ginkgo biloba have proved especially interesting and are commercially available in Europe for the treat- ment of various circulatory disorders. → Certain fish oils (e.g. cod-liver, halibut-liver) once employed solely for their vitamin contents have recently received a resurgence‫ اﻧﺘﻌﺎش طﻔﺮة‬in popularity as dietary supplements. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 5- Oral anticoagulants These compounds inhibit the clotting mechanism of the blood and are of value in arterial thrombosis; they have no effect on platelet aggregation. One group of active drugs constitutes the 4-hydroxy-coumarins which act by antagonizing the effects of vitamin K. Warfarin sodium is one of the most widely used drugs. Plants used in herbal medicine which contain coumarin derivatives and possess antivitamin K activity include Melilotus officinalis‫ﺣﻨﺪﻗﻮق ﺣﻘﻠﻲ‬, Galium aparine and Lavandula officinali ‫ﻻﻓﻨﺪر‬/‫ﺧﺰاﻣﻰ‬. → Other anticoagulants are heparin, which is given by injection, and hirudin, produced by the leech ‫ ;ﻋﻠﻖ‬hirudin, a polypeptide of 65 amino acids, can also be obtained from genetically modified Saccharomyces (genus of fungi that includes many species of yeasts). Phytotherapy and chem. of Home work: look for the therap. uses of leech natural products Dr. Khaled Tawaha What is the difference between anticoagulant and antiplatelet? Anticoagulants slow down clotting, thereby reducing fibrin formation and preventing clots from forming and growing. Antiplatelet agents prevent platelets from clumping and also prevent clots from forming and growing. Does vitamin K occur naturally in the body? Where in the body is vitamin K made by bacteria? The major source of vitamin K1 is found in green plants. This form is called phylloquinone(K1). Another form of vitamin K is made by bacteria living in the intestine. This form is called menaquinone(K2).  How do I know if I need vitamin K?  To diagnose a vitamin K deficiency, a doctor will ask about a person's medical history to see if they have any risk factors. The doctor may use a coagulation test called the prothrombin time or PT test. They take a small blood sample and then add chemicals to observe how long it takes to clot. VIT.K1 ( LEAFY GREEN VEGETABLES) VIT.K2 ( CEREALS, FATTY MEAT, EGGS AND FISH, BACTERIA IN THE LARGE INTESTINE ARE ALSO KNOWN TO SYNTHESIZE VITAMIN K2) VIT.K3 (IS A SYNTHETIC FORM OF VITAMIN K) Why do we use warfarin? Warfarin is prescribed for people who are at increased risk for developing harmful blood clots. This includes people with a mechanical heart valve, an irregular heart rhythm called atrial fibrillation, certain clotting disorders, or a higher risk of a clot after hip or knee surgery. Drugs acting on blood vessels →Peripheral vasoconstrictor drugs 1- Ergotamine (tartrate) from Claviceps purpurea : Produces a direct constrictor effect in vascular smooth muscle; the reversal of the dilation of cranial vessels leads to its use at the onset of classical migraine. 2-Ergotoxine : similar to ergotamine. 3- Nicotine: promoting release of vasopressin and adrenaline. Phytotherapy and chem. of natural products Dr. Khaled Tawaha →Vasodilator drugs 1- Papaverine (an opium alkaloid) Acts directly on the blood vessels by causing relaxation of smooth muscle. An intravenous injection used for the treatment of pulmonary arterial embolism. 2- Xanthine derivatives (caffeine, theobromine, theophylline): As papaverine; they also have a central vasoconstrictor action counteracting the peripheral effect. Also diuretic * Ergotamine: Adrenaline antagonist *Reserpine: Vasodilatation is produced by a peripheral and central action. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Hypolipidaemic drugs Phytotherapy and chem. of natural products Dr. Khaled Tawaha In recent years much prominence ‫ اﺑﺮاز اھﻤﯿﺔ‬has been given to the association of high levels of blood cholesterol and plasma triglycerides with atherosclerosis and ischaemic heart disease. Treatment of hyperlipidaemia is preferably dietary accompanied by other natural regimes. Drug therapy is reserved for the more intractable conditions. → Natural products having a beneficial action include nicotinic acid and those fish oils containing high quantities of ώ-3-marine triglycerides. The latter involve eicosapentaenoic acid and docasahexaenoic acid which, when counting from the methyl end, possess the first double bond at C-3. Phytotherapy and chem. of natural products Dr. Khaled Tawaha → Garlic (Allium sativum) for the treatment of various cardiovascular conditions remain a subject extensive investigation.→ the majority of published data supports the hypothesis that garlic lowers serum total cholesterol and improves the lipid profile. → There is a tendency towards reduction of low-density lipoprotein and an increase in high-density lipoprotein giving a more favorable HDL:LDL ratio. Phytotherapy and chem. of natural products Dr. Khaled Tawaha  ACTION ON THE GASTROINTESTINAL TRACT Phytotherapy and chem. of natural products Dr. Khaled Tawaha Bitters: At one time these were extensively used in liquid medicaments to stimulate appetite. The bitter constituents stimulate the gustatory nerves in the mouth and give rise to an increase in the psychic secretion of gastric juice. → Extracts of the following drugs have been so employed: gentian, quassia,calumba, cinchona (or quinine), nux vomica (or strychnine). 2- Anticholinergic drugs In this capacity hyoscine and hyoscyamine help disturbances caused by gastric mobility and muscle spasm particularly with some ulcer patients. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 3- Emetics →Ipecacuanha preparations ‫ﻋﺮق اﻟﺬھﺐ‬ (Cephaelis ipecacuanha):on oral administration, have a delayed emetic action produced by irritation of the mucous membranes. → Picrotoxin stimulates the vomiting centre through its general effect on the central nervous system 4- Anti-emetics →Ginger(‫زﻧﺠﺒﯿﻞ‬/Zingiber officinalis) has received scientific approval for the prevention of the symptoms of travel sickness. →Cannabis affords sickness relief to patients undergoing chemotherapy. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 5- Carminatives: (a drug that relieves flatulence): These are aromatic substances which assist the eructation ‫ ﺗﺠﺸﺆ‬reflex; their mode of action is obscure ‫ﻣﺒﮭﻢ‬. →Dill oil(‫) اﻟﺸﺒﺚ‬is used for the relief of flatulence, especially in babies. →Other plants or oils used as carminatives include caraway(Carum carvi )‫ﻛﺮاوﯾﺔ‬,fennel, peppermint, thyme, nutmeg, calamus, pimento, ginger, clove, cinnamon, chamomile. → Chalk(is a soft, white, porous, sedimentary carbonate rock, a form of limestone composed of CaCO the mineral calcite. Calcite is an ionic salt called calcium carbonate or 3. It forms under reasonably deep marine conditions from the gradual accumulation of minute calcite shells (coccoliths) shed from micro- organisms called coccolithophores is used as an antacid → Charcoal (is a form of carbon processed to have small, low-volume pores that increase the surface area available for adsorption (Activated carbon is used to treat poisonings and overdoses following oral ingestion. Tablets or capsules of activated carbon are used in many countries as an over-the-counter drug to treat diarrhea, indigestion, and flatulence as an adsorbent. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 6- Ulcer therapy : →Derivatives of glycyrrhetinic acid ‫(ﻋﺮق اﻟﺴﻮس‬a triterpenoid of liquorice root).→ Other antiulcer agents include alginic acid, marshmallow and comfrey. 7- Demulcents These sooth and protect the alimentary tract and overlap with some materials used in ulcer therapy. → Iceland moss, orris. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 8- Laxatives and purgatives( are substances that loosen stools and increase bowel‫ اﻣﻌﺎء‬movements). They are used to treat and prevent constipation : Purgatives may be classed according to their mode of action: 1- Hydrophilic colloids which function as bulk- producing laxatives →Agar, Psyllium. 2- An indigestible vegetable fibre which absorbs water and provides bulk →Bran. 3- Contains anthraquinone derivatives which are hydrolyzed in the bowel to stimulate Auerbach's plexus in the wall→ Cascara, rhubarb‫راوﻧﺪ رﺑﺎص‬, aloes As senna. 4- Contains glycerides which on hydrolysis yield riconoleic acid, irritant to the small bowel→ Castor oil. 5- Drastic purgatives→Podophyllum resin, colocynth(now little used for this purpose. They were often prescribed with belladonna to reduce griping. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 9- Rectal and colonic drugs →Arachis oil, esculin, hamamelis, pilewort and balsam of Peru are examples of this group; they include those used in suppositories. 10- Antidiarrhoeal drugs → Morphine and codeine act by increasing the smooth muscle tone of the bowel and by reducing its mobility. →Commonly prescribed with kaolin. Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE NASAL AND RESPIRATORY SYSTEMS Phytotherapy and chem. of natural products Dr. Khaled Tawaha 1- Aromatic inhalations →Benzoin, cineole, eucalyptus oil, menthol and peppermint, pumilo pine oil, balsam of Tolu, thymol, turpentine. 2-Bronchodilators and nasal decongestants → xanthines(theophylline,→ asthma). 3-Expectorants senega root, liquorice root(?!), , tolu balsam, grindelia, angelica root and leaf, storax , coltsfoot(?!),bloodroot. Phytotherapy and chem. of natural products Dr. Khaled Tawaha 4-Antiexpectorants → Codeine, atropine. 5- Cough depressants →Morphine(?!), codeine, noscapine, wild cherry. 6-Demulcents → Marshmallow, verbascum, plantago,Iceland moss, honey. Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE LIVER Phytotherapy and chem. of natural products Dr. Khaled Tawaha The liver, the principal organ of metabolism and excretion, is subject to a number of diseases which may be classed as liver cirrhosis (cell destruction and increase in fibrous tissue), acute or chronic hepatitis (inflammatory disease) and hepatitis (non inflammatory condition). →The most common drug of plant origin used in Western medicine for its antihepatotoxic properties is Silybum mariananum Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE URINARY AND REPRODUCTIVE SYSTEMS Phytotherapy and chem. of natural products Dr. Khaled Tawaha  1-Diuretics:  →Xanthine derivatives as present in many beverages (tea, coffee, etc.) promote dilation of the renal modularly blood vessels.  →Digitalis glycosides improve the failing heart thereby increasing renal perfusion and glomerular filtration; hence, Withering's original introduction of digitalis for the treatment of dropsy. There is also a small but finite effect on tubular re-absorption of sodium ions Phytotherapy and chem. of natural products Dr. Khaled Tawaha 2-Diuretics and urinary antiseptics: →Buchu, bearberry, juniper, copaiba. These include drugs used for the treatment of cystitis‫ اﻟﻤﺜﺎﻧﺔ‬and urethritis. 3-Drugs acting on the uterus →Preparations of ergot were traditionally used in childbirth and then largely replaced by the isolated alkaloid ergometrine. Administered as its salts it has a direct stimulant action on the uterine muscle and reduces the incidence of postpartum hemorrhages‫ﻧﺰﻳﻒ ﻣﺎ ﺑﻌﺪ اﻟﻮﻻدة‬. Ergotamine acts similarly but is not suitable for obstetric‫ اﻟﺘﻮﻟﯿﺪي‬use because of its marked peripheral vasoconstrictor action 4-Oral contraceptives: 5-Male impotence: → Papaverine (under careful medical supervision), yohimbine Phytotherapy and chem. of (erectile dysfunction) natural products Dr. Khaled Tawaha Benign prostate hyperplasia (BPH) →activity A number of phytomedicinals are employed (often as admixtures) to treat the symptoms of BPH. →Two metabolites associated with the condition are dihydrotestosterone and oestrogen which require two enzymes (5a-reductase and aromatase) for their synthesis in the body. →It has been shown, for some of the drugs used, that they are inhibitors of these two enzymes. →The following examples are well-established: →Cucurbita pepo seeds (pumpkin ‫)اﻟﻘﺮع‬, Epilobium angustifolium, Prunus africana (Pygeum africanum) bark, Serenoa repens fruits (saw palmetto ‫اﻟﺒﻠﻤﯿﻂ اﻟﻤﻨﺸﺎري‬, sabal), Urtica dioica and U. urens root extracts. Phytotherapy and chem. of natural products Dr. Khaled Tawaha THE SKIN AND MUCOUS MEMBRANES Phytotherapy and chem. of natural products Dr. Khaled Tawaha 1-Emollients and demulcents These include a number of vehicles used in the preparation of ointments, creams, lotions, etc., and include: → fixed oils (e.g. olive, arachis, coconut, theobroma) →fats (wool-fat, lard). →waxes of animal origin (beeswax, spermaceti), →gums (acacia, tragacanth) and mucilages (psyllium, elmbark). 2-Adsorbents →Starch, alginates, charcoal. 3-Astringents →Tannins (e.g. Tannic acid), krameria, galls, hamamelis, pomegranate rind ,kinos Phytotherapy and chem. of natural products Dr. Khaled Tawaha 3- Counter-irritants →Camphor, capsicum, methyl salicylate, mustard seed. 4- Anti-inflammatory agents →Corticosteroids used locally, matricaria, arnica 5- Psoriasis and Eczema treatment →Comfrey, allantoin, evening primrose oil, and others. 5-Wound coverings →Type of wound covering (occlusive, non occlusive, haemostatic) is important in the healing process. See alginates, cotton. Phytotherapy and chem. of natural products Dr. Khaled Tawaha ACTION ON SUGAR METABOLISM Many plants have been used in traditional systems of medicine for the oral treatment of diabetes. → karela fruit (Momordica charantia), cumin fruit, ginseng, Teucrium oliveri anum, neem (Azadirachta indica), onion, Aloe spp. Phytotherapy and chem. of natural products Dr. Khaled Tawaha  STEROIDAL AND ANTI- INFLAMMATORY DRUGS Phytotherapy and chem. of natural products Dr. Khaled Tawaha Two types of corticosteroidal hormone are the glucocorticoids, which regulate carbohydrate and protein metabolism and which also possess a strong anti-inflammatory action, and the mineralocorticoids, which influence the electrolyte and water balance of the body. →These hormones are produced naturally in the adrenal cortex but a wide variety of semi-synthetic drugs of this type is commonly in use. These are synthesized using plant steroids as intermediates; diosgenin and hecogenin being the principal sources. To a lesser extent the steroidal alkaloids of the Solanaceae are employed. There is a large world demand for these compounds, particularly for the synthesis of oral contraceptives Phytotherapy and chem. of natural products Dr. Khaled Tawaha NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Phytotherapy and chem. of natural products Dr. Khaled Tawaha →Aspirin, first synthesized in 1853 by Carl Gerhardt, is still one of the most widely- used mild analgesic and nonsteroidal anti-inflammatory drugs (NSAID). →It had its medicinal origin in the salicylates and glycosides of willow bark. long used for the treatment of rheumatic diseases, gout and painful conditions of all types. Enzymes have been used to detect anti-inflammatory activity of plants-galangin, a flavonoid of Alpinia officinarum (Zingiberaceae; galangal rhizome) was found to be a cyclo-oxygenase inhibitor. →Echinacea purpurea root. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Willow Bark,matricaria flowers (Chamomilla recutita, German chamomile)→ treatment of acute gastritis(flavonoids), Calendula officinalis (terpenoids); liquorice root (Glycyrrhiza glabra) both the triterpenoid saponin glycyrrhizin and the flavonoids have, among their other pharmacological actions, anti-inflammatory activity. Colchicine, an alkaloid of Colchicum autumnale. is the classical drug for the treatment of acute attack of gout. Phytotherapy and chem. of natural products Dr. Khaled Tawaha →It he dried root of Harpagophytum procumbens (Devil's claw) (Pedaliaceae), has recently received popular attention for the treatment of painful rheumatic conditions; iridoid glycosides, e.g. harpagoside, are the characteristic constituents. →The juice of Ananas comosus. the pineapple (Bromeliaceae) contains a mixture of at least five proteolytic enzymes collectively called bromelin or bromelain. In Western medicine the enzyme has been introduced for its ability to dissolve fibrin in conditions of inflammatory oedema. →The action of ginkgolides (C2o terpenes from Ginkgo biloba) as potent antagonists of platelet activating factor has already been mentioned. Phytotherapy and chem. of natural products Dr. Khaled Tawaha TREATMENT OF INFECTIONS Phytotherapy and chem. of natural products Dr. Khaled Tawaha  Antibiotics Many higher plants possess constituents having antibacterial properties; none has been utilized clinically, mainly because of high toxicity. Moulds and streptomyces are the principal sources; see Chapter 32 for a consideration of antibacterial and antiviral drugs. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Antimalarials →quinine, isolated from the bark of various Cinchona spp and is of some resurgent importance for combating malarial organisms resistant to other drugs. →Artemisinin (Ginghaosa), an unusual sesquiterpene lactone, is the active constituent of an ancient Chinese drug derived from Artemisia annua. It is effective against chloroquine (synthetic) resistant strains of Plasmodium vivax and P. falciparum as well as against cerebral malaria. Phytotherapy and chem. of natural products Dr. Khaled Tawaha Amoebicides →Emetine An alkaloid of ipecacuanha root, used as its hydrochloride or bismuth iodide in the treatment of amoebic dysentery. Complete eradication of the chronic infection is difficult and combined therapy with other drugs is often necessary. Anthelminthics Extract of male fern for tapeworm infections Santonin possesses a powerful action in paralysing round-worms; although once extensively used its high toxicity has led to replacement by piperazine - Oil of Chenopodium→like santonin( used also in hookworm disease). Phytotherapy and chem. of natural products Dr. Khaled Tawaha  TREATMENT OF MALIGNANT DISEASES →Catharanthus roseus= Vinica rosea → Taxus brevifolia and T. baccata Phytotherapy and chem. of natural products Dr. Khaled Tawaha  TREATMENT OF ALLERGIES A large number of materials give rise to allergic conditions in sensitive individuals. Extracts containing specific allergies are available as dia- gnostic kits or for desensitization. Examples of plant allergens are grass, flower and tree pollens, dried plants and moulds (see Chapter 40: Trease and Evans; Pharmacognosy). Phytotherapy and chem. of natural products Dr. Khaled Tawaha  THE IMMUNE SYSTEM Drugs affecting the immune system are termed immunomodulatory or adaptogenic. →Ginseng : Panax ginseng →Echinacea spp: E. pupurea Phytotherapy and chem. of natural products Dr. Khaled Tawaha