Chemistry of Drugs Lecture Notes PDF

CHEMISTRY OF DRUGS The living organism may be considered a biosynthetic laboratory not only for chemical compounds (carbohydrates, proteins,fats) that are utilized as food by humans and animals. but also for a multitude of compounds (glycosides, alkaloids, terpenes) that exert a physiologic effect....

CHEMISTRY OF DRUGS The living organism may be considered a biosynthetic laboratory not only for chemical compounds (carbohydrates, proteins,fats) that are utilized as food by humans and animals. but also for a multitude of compounds (glycosides, alkaloids, terpenes) that exert a physiologic effect. These chemical compounds give plant and animal drugs their therapeutic properties ‫ﻟﻤﺎ ﻧﺪرس اﻟﻜﺎﺋﻦ اﻟﺤﻲ ﺑﻨﻼﻗﯿﮫ ﻋﺒﺎرة ﻋﻦ ﻣﺨﺘﺒﺮ ﻹﻧﺘﺎج ﻣﺠﻤﻮﻋﺔ ﻣﺘﻨﻮﻋﺔ ﻣﻦ اﻟﻤﺮﻛﺒﺎت‬ primary compounds ‫ ﺑﺮﺿﮫ ال‬chemical compounds ‫ ﺑﺮﺿﮫ ﻣﺶ ﺑﺲ‬،‫اﻟﻜﯿﻤﯿﺎﺋﯿﺔ‬ (‫اﻟﻲ ھﻤﺎ اﻟﻜﺮﺑﻮھﯿﺪرات واﻟﺒﺮوﺗﯿﻨﺎت واﻟﺪھﻮن) ﯾﻨﺘﻔﻊ ﺑﮭﺎ اﻹﻧﺴﺎن واﻟﺤﯿﻮاﻧﺎت ﻛﻤﺼﺪر ﻟﻠﻐﺬاء‬ glycosides ‫ اﻟﻲ ھﻤﺎ ال‬secondary compounds ‫وﻋﻨﺎ ﺑﺮﺿﮫ ال‬ ‫ اﻟﻲ ﺑﻌﻄﻮا ﺗﺄﺛﯿﺮات ﻓﺴﯿﻮﻟﻮﺟﯿﺔ‬terpenes‫و‬alkaloids‫و‬ :‫ب حيوي يصنع‬7 ‫اذا النبات عبارة عن‬ Primary compounds:‫ يوجد حياة للكائن الحي‬7 ‫سميت بذلك )نها مهمة جًدا للحياة بدونها‬ Secondary compounds:glycosides,alkaloids and terpenes secondary ‫نسان هي عبارة عن‬L‫واد بالنسبة للنبات الها وظيفة معينة ولكن بالنسبة ل‬C‫ممكن تكون هذه ا‬ pharmacological or physiological ‫واد( الي الها‬C‫) أغلب ما يهمنا في ا)دوية النباتية هي هاي ا‬ ‫ بتعطينا أهمية النبات هاد لشو‬secondary compounds ‫اذا هيك عرفنا انه ال‬. effect Phytotherapy and chem. of natural products Dr. Khaled Tawaha  Drugs are used as such in their - crude form extract aqueous alcoholic- * : , - or they may be extracted Ingredients when drugs are extracted → the resulting principles (constituents) being employed as medicinal agents Because the plant or animal is composed of many chemical compounds, it is common practice to single out those compounds that are responsible for the therapeutic effect and to call them : active constituents. ‫ﻧﻈًﺮا ﻷن اﻟﻨﺒﺎﺗﺎت واﻟﺤﯿﻮاﻧﺎت ﺗﺘﻜﻮن ﻣﻦ اﻟﻌﺪﯾﺪ ﻣﻦ اﻟﻤﺮﻛﺒﺎت اﻟﻜﯿﻤﯿﺎﺋﯿﺔ )ﯾﻌﻨﻲ اﻧﺖ ﻟﻤﺎ ﺗﺸﺮب ﻗﮭﻮة ﻣﺎ ﺑﺘﻜﻮن ﺑﺲ ﺑﺘﺸﺮب ﻛﻔﺎﯾﯿﻦ ﻟﺤﺎل ﻻ‬ ‫ ﻣﻦ ﺑﯿﻨﮭﻢ اﻟﻜﻔﺎﯾﯿﻦ( ﻓﺈن ﻣﻦ اﻟﺸﺎﺋﻊ ﺗﺤﺪﯾﺪ ﺗﻠﻚ اﻟﻤﺮﻛﺒﺎت اﻟﺘﻲ ﺗﻜﻮن ﻣﺴﺆوﻟﺔ ﻋﻦ اﻟﺘﺄﺛﯿﺮ اﻟﻌﻼﺟﻲ وﺑﻨﺴﻤﯿﮭﺎ‬multi compounds ‫ﺑﺘﻜﻮن ﺑﺘﺸﺮب‬ ‫ ﺑﺲ ھﻮ اﻧﺖ ﻣﺶ ﺑﺲ ﺑﺘﺎﺧﺪ ﻛﻔﺎﯾﯿﻦ ﻟﺤﺎل ﻻ ﺑﻞ‬،‫"اﻟﻤﻜﻮﻧﺎت اﻟﻔﻌﺎﻟﺔ" ﯾﻌﻨﻲ ﺑﻤﺜﺎل اﻟﻘﮭﻮة اﺣﻨﺎ ﺑﻨﺸﺮب اﻟﻘﮭﻮة ﻋﺸﺎن ﺑﺪﻧﺎ ﻛﻔﺎﯾﯿﻦ ﻓﮭﻲ اﻟﻤﺎدة اﻟﻔﻌﺎﻟﺔ‬ theobromine ‫ ﺑﺪل ﻣﺎ ﺗﺸﺮب ﻛﺎﺳﺔ ﻗﮭﻮة ﻓﯿﮭﺎ‬caffeine tablets ‫ھﻨﺎك ﻣﻮاد ﻛﺜﯿﺮة وﻟﻜﻦ اذا ﺑﺪك ﻛﻔﺎﯾﯿﻦ ﻟﺤﺎل ﺑﺘﺮوح ﻋﻠﻰ اﻟﺼﯿﺪﻟﺔ ﺑﺘﺸﺘﺮي‬. theophylline ‫و‬ These active constituents are differentiated from inert constituents ( cellulose, lignin, suberin , and cutin) · 9.jj lignin ing > - --- · suberie , , b cellulose in addition, other substances may have no definite pharmacologic activity and also are considered inert constituents ( starch, albumin, coloring matters, and other substances ) activepharmacological pharmaceutical & active · Mill 5 d -active constituents /: - 1 Is [catin , suberin , lignin , cellulose] desis' 56s - est constituents < [coloring matters , Albumin , Stach 2 , Zols as &Is → In animal drugs, keratin, chitin, muscle fiber, and connective tissue are regarded as inert. C414 ! us problem ! Often the presence of inert substances may modify or prevent the absorbability or potency of the active constituents ‫واد‬/‫واد الفعالة أو ممكن تعدل وتزيد من امتصاص ا‬/‫ ممكن تعيق امتصاص ا‬inert substances ‫ال‬ ‫الفعالة‬ Solution ! To eliminate the undesirable effects of inert matter in the crude drug or its preparations.  relimination active principles are extracted, crystallized, and purified for therapeutic use ‫بعدها‬crystallization‫ بعدها‬extraction ‫ص‬9‫ بنعمله استخ‬crude drug ‫ول نجيب ال‬+‫النبات 'زم با‬ ‫ادة الفعالة النقية وبنستخدمها‬B‫ بعدها بنحصل على ا‬purification These constituents have been referred to as “secondary” plant substances. Active constituents may be divided into two classes: 1-pharmaceutically active 2-pharmacologically active 1-pharmaceutically active May cause precipitation or other chemical changes in a medicinal preparation. For instance, neither cinchona bark nor its extracts could be used in formulating preparations containing iron salts because the cinchotannic acid would combine with these salts and cause precipitation. ‫ تاعه هل يمكن‬extract ‫ أو ال‬cinchona bark ‫ فيها وبدي أضيف‬iron ‫ وبدي أصنعها يعني عندي خلطة وفي عندي‬formula ‫عندي‬ iron ‫ مع ال‬combination ‫ بعمل‬extract ‫ وال‬crude drug ‫ الي موجود بال‬cinchotannic acid ‫نه ال‬+ ‫أعمل هاد ا'شي؟ ' ليش؟‬ ‫ وبصير في ترسيب بالتحضيرة وهاد غير جيد‬salt ↑ pharmaceutical active because it cause precipitation *Cinchotannic acid, then, is active constituent Solution ! The use of quinine hydrochloride obviates this incompatibility because it is a purified crystalline compound that does not contain the slightest trace of cinchotannic acid. ‫ 'نها ما بتحتوي على أي‬incompatibility ‫ادة النقية بتبعد عنك ال‬B‫ ا‬quinine hydrochloride ‫طيب شو الحل؟تستخدم فقط‬ iron ‫رغوب الي بعمل ترسيب مع ال‬B‫ فهيك بنتجنب تفاعلها غير ا‬cinchotannic acid ‫أثر لل‬ ‫ للضغط العالي‬reserpine ‫ا أقلك ال‬B 2-pharmacologically active analgesic ‫ هو‬morphine ‫ا أقلك ال‬B Are responsible for the therapeutic activity of the drug. They may be either : -- Single chemical substances Are exemplified by sugars, starches, plant acids, enzymes, glycosides, steroids, alkaloids, proteins, hormones, and vitamins -- Mixtures of principles include fixed oils, fats, waxes, volatile oils, resins, oleoresins, oleo- gum-resins, and balsams ? crude I s drugs PRODUCTION OF CRUDE DRUGS E - - = impress 1 ) starting material : plants these plants are either cultivated or wild plants - : 1 J 144 - CULTIVATED AND WILD PLANTS 1-Certain drugs are now obtained almost exclusively from cultivated JN1 - plants: ‫نسان بزرعها مش من البرية‬5‫نباتات بنحصل عليها عن طريق ا‬ cardamoms, Indian hemp, ginger, and pepper mint and spearmint - for oil production, fennel, cinchona and opium.poppy. 2-Others are now grown ‫نباتات موجودة بالبرية ولكن بكميات غير كافية فبنزرعها‬ because supplies of the wild plants are insufficient to meet the demand - collection &% 5 or because, owing to sparse distribution or collection is difficult. 3-Cultivation is essential in the case of drug such as Indian hemp and opium, which are subject to government control. opium poppy ‫ أو‬indian hemp ‫ردنية وبدك تعمل بحث تقوم تزرع‬/‫تخيل انت بالجامعة ا‬ ‫زم تخبرهم وتاخد ترخيص‬F‫بدون ما تخبر الحكومة بتروح فيها ف‬  cultivationsl 20% 4-In many cases cultivation is advisable because of the improved quality of the drug which it is possible to produce. ‫ و‬species ‫أحيانا ً في نباتات بكون الها‬ The improvement may be due the following: - ‫ة فلأتححسصنل تعكلوىن امنحتصمنوتلقي‬subspecies ‫البذورالصحيح‬ A) The power to confine collections to species, ‫واد الفعالة فيه أكثر‬G‫أفضل وا‬ varieties which have the desired phytochemical characters (cinnamon, fennel, cinchona Labiate drugs and valerian) B)The better development of the plants owing to improved ‫ الهم اذا صابوا النبات‬control ‫بتعمل‬ conditions of the soil control of insect pests. fungi, etc - - ‫صنع تاع‬G‫تصور لو زارع جمب ا‬ C) The better facilities for treatment after collection. - ‫دوية النباتية نباتات بكون سهل اذا‬X‫ا‬ ‫ما في شتاء تسقيهم سهل تداويهم لو‬ ‫رض أو حشرات‬G ‫تعرضوا‬ *For example drying at a correct temperature in the cases of digitalis, peeling of cinnamon and ginger. *For success in cultivation it is necessary to study the conditions under which the plant flourishes in the wild state and reproduce the conditions or improve on them. pit> Ja 5550 S - -. 156 ass - - & jgis 55 2 ‫نسان مو صايبه بكون‬6‫ا يكون حي وا‬. ‫ النبات‬+‫ ه‬glycosides ‫ فيه‬digitalis ‫نبات ال‬ # ‫ للنبات‬collection ‫ا تعمل‬. ‫ بس‬not active ‫في إنزيمات نايمة ما بتعمل أي اشي‬ collection ‫ في هيك إنزيم بكون نايم وبس نعمل‬digitalis ‫نزيمات هاي فبال‬6‫بتصحى ا‬ sugar ‫ بصير عنا ال‬hydrolysis for the glycoside ‫نزيم وببلش يعمل‬6‫بصحى ا‬ ‫ لل‬collection ‫ لحال وهاد غير مرغوب شو الحل؟ بعد ما نعمل‬non sugar ‫لحال وال‬ ‫ناسبة وبحالة ال‬.‫حصول فيه ونختار الحرارة ا‬.‫ ونضع ا‬oven ‫ بكون في‬digitalis stopping for the enzyme action ‫ السريعة هاي بنعمل‬drying SOILS "T" ‫زم نشوف التربة >نه مو كلها واحد كل تربة الها صفات وفي أنواع‬4 ‫بدنا نجيب نبات ونزرعه أول اشي‬ ‫تربة حمراء وصفراء والي فيها حصى والي ما فيها حصى فالها للتربة صفات كيميائية وفيزيائية‬ 2 ) The soil ‫يكروبات الي بتعيش فيها( لهيك مو كل التربة واحد‬S‫وميكروبيولوجية )الي هو ا‬ THREE IMPORTANT BASIC CHARACTERISTICS OF SOILS ARE The physical, chemical and microbiological properties. 1-Variations in partiele size result in different soils ranging from clay,via sand,to gravel 2-Particle size is one factor influencing water-holding capacity → some plants (e.g. Althaea officillalis) which produce mucilage as a water-retaining material contain less mucilage when grown on soil with a high moisture content 3-Although particular species have their own soil pH tolerances - Datura stramonium → pH = 6.0-8.2 - Majorana hortensis → pH = 5.6-6.4), no marked influence of pH value within the tolerance range has been demonstrated for essential oils (Mentha piperita) and alkaloids (D. stramonium). *Nitrogen fertilization has been shown to increase the silymarin content of the fruits of Silybum marianum. ↳ Milk thistle I ‫ وجدوا انه اذا‬silymarin ‫أهم مادة بالخرفوش ال‬ st X j - jijj ‫بنسمد في السماد النيتروجيني بزيد من نسبة ال‬ fruit ‫ في ال‬silymarin - /195i Fruits seeds -j  dis PROPAGATION FROM SEEDS % jzjad 3 ) The seeds. oslingin. , 9 I ↑ · is 25% e 1-To ensure success the seeds must be collected when perfectly ripe If not planted immediately, they should normally be stored in a cool and dry place. > i so - sd" is "germinationslas ~ 2- ↑ & (Jesisjjodig - 1.Some seeds such as cinnamon , coca and nutmegs Ed9)5 9 ja % rapidly lose their power of germination if allowed to dry or if stored for quite short periods = jd/1/201 > - 2.Long storage of all seeds usually much decreases the percentage which germinate. -105? Jadizi- = 25gjj'Js ↑ -sidijt ; sys Say 3-In some cases, however, immediate sowing of the fresh seed is d advisable · dis11 js= For example It has been shown that if the seeds of Colchicum autumnale are (3-4 days) - %100 , S S/i air-dried even for a few days, only about 5% germinate in 1 year , - and some may not germinate for 5 years; whereas if sown as 9 /sid 563 js Jes %9. soon as the capsules dehisce, 30% will germinate in the first year. - & J- With Erythroxylum coca and E. novogranatense - the seeds stored at 4°C for 24 days gave, ↑ Jg'g I jgT respectively, dis Si & Erythroxylum coca → 29% Few days E. novogranatense → 0% germination  Seeds may, if slow germinating, be soaked in water or a 0.2% solution of gibberellic acid for 48 hrs before sowing 11 Is Time of seed sowing may affect the active constituents, as illustrated by Chamomilla recutita for 17 cultivars investigated most gave a significantly higher yield of volatile oil if they were spring-sown rather than autumn-sown and the oil composition also varied