Nature and sources of drugs,PHARMACOLOGY .pptx

NATURE AND SOURCES OF DRUGS,PHARMACOLOGY

1. Nature and sources of drugs Dr. A quib A hmed S haik PG M D P harmacology GMC-ANANTAPUR

2. Discovery of source in history Discovered in 1928 by Alexander Fleming, the drug was made medically useful in the 1940s by a team of Oxford scientists led by Australian Howard Florey and German refugee Ernst Chain. In September 1928 the bacteriologist Alexander Fleming returned to St Mary’s Hospital and Medical School in London after taking a holiday. Before leaving, he had set a number of petri dishes containing Staphylococcus bacteria to soak in detergent. Fleming noticed that one dish had not been covered by detergent and had become contaminated with mould . This particular mould , seemed to be producing a substance that was killing the bacteria around it. Further tests conducted by Fleming confirmed the anti-bacterial properties of the substance he called ‘penicillin ’, derived from P encillium notatum . Penicillin has since saved countless lives.

3. objectives Definitions of pharmacology, pharmacognosy and drug. Description of nature of drugs based on physical nature, form and actions with examples. Discuss & explain the Classification of sources of drugs based on sourcing and modes of preparation with examples.

4. contents Pharmacology Drug Nature of drugs chemical nature Physical nature According to action Pharmacognosy Source of drugs Natural Synthetic Plant sources Animal sources Microbiological sources Marine sources Mineral sources Genetically engineered Monoclonal antibodies Semi synthetic & synthetic References

5. Pharmacology It is the science that deals with drugs, science of substances used to prevent, diagnose and treat disease. Covers all aspects of knowledge (detailed study) of drugs, particularly their actions on living animals, organs and tissues.

6. drug Any substance or product that is used or intended to be used to modify or explore physiological systems or pathological systems or pathological states for the benefit of recipient .

7. Nature of drugs Substance that brings about a change in biologic function through its chemical action. All drugs are chemical entities with simple or complex molecules. Drugs may be synthesized within the body (e.g. - Hormones) or may be chemicals not synthesized in the body (xenobiotics). In most cases, the drug molecule interacts as an agonist(activator) or antagonist(inhibitor) with a specific molecule called receptors in biologic system which plays a regulatory role. Contd..

8. Nature of drugs Few drugs (osmotic agents) interact almost exclusively with water molecules, in very small cases some drugs (chemical antagonists) may interact directly with other drugs. Drugs interact with receptors by means of chemical forces or bonds, these are three major types - covalent, electrostatic and hydrophobic. To interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape and atomic composition. Contd.

9. Nature of drugs Size/ molecular weight should be in the range of 100 - 1000 D (Daltons). 1D = 1g/mol 1 KD (kilo Daltons) = 1000 D * If smaller than 100D, they do not generally have a specific feature in terms of shape, size, configuration, chirality, distribution of charges etc. to selectively bind to one/few closely related target biomolecules to the exclusion of others. * Molecules larger than 1000 D do not readily pass-through membrane barriers in the body to reach target sites in various tissues/cells. * Exception: 7D – Lithium ions, 10-20 KD – heparin, >30 KD – Gonadotropins, >50 KD – enzymes, proteins, antibodies. Contd.

10. Nature of drugs It must have the necessary properties to be transported from its site of administration to its site of action. Finally, should be inactivated or excreted from the body at a reasonable rate so that its actions will be of an appropriate duration.

11. Nature of drugs Chemical nature : Organic – majority of drugs Weak acids –aspirin, penicillin. Weakly basic – morphine, chloroquine. Non-electrolytes – alcohol, diethyl ether.

12. Nature of drugs Inorganic – a number of useful or dangerous drugs like lithium, iron and heavy metals. Ex: - Ferrous sulfate, Zinc sulfate, Magnesium sulfate, Lithium carbonate, etc.

13. Nature of drugs Physical nature: On room temperature drugs can be solids, liquids and Gaseous states I. Solids Ex: - paracetamol, furosemide, ampicillin, etc. II. Liquids Ex: - ethanol, glycerol trinitrate, propofol, etc. III. Gaseous Ex: - nitrous oxide, etc.

14. Nature of drugs According to their action: Preventive/ prophylactic: Those drugs used to prevent the cause of the disease . Ex: - Aspirin, clopidogrel, dipyridamole, etc. - blood thinners – heart diseases & stroke. Atorvastatin, Rosuvastatin, Fluvastatin, etc. – HMG CoA reductase inhibitors- cholesterol lowering medicines.

15. Nature of drugs Symptomatic: used to treat the symptoms of the disease, not the underlying cause. Supportive or palliative treatment. Ex: - Ispaghula – bulking agent – constipation. Diclofenac & ibuprofen – NSAIDs – analgesics(pain).   Diagnostic: helps to determine the treatment or nature and causes of disease. Ex: - Fluorescein – dye – angiography Sodium iodide-I-131 – radioactive substance – thyroid scans.

16. Nature of drugs Curative: drugs used in treatment with intent of fully resolving any illness or disease. Ex: - penicillin – antibiotic – systemic infections Vincristine – Vinca alkaloids – chemotherapy POP cast – bone fractures setting.   Health maintenance drugs: helps in maintain our health to treat the illnesses that are considered chronic or long-term. Ex: - Levocetrizene – anti- histaminics – respiratory illness & allergies. Enalapril , Lisinopril – ACE inhibitors – heart disease & high BP.

17. Nature of drugs * Contraceptive: medicines that are used to prevent unwanted pregnancy (birth control). Ex: - OCP, COCP, Medroxyprogesterone etc.

18. Sources of drugs Pharmacognosy: Science or study of the sources and identification of drugs from various sources such as plants, minerals, animals etc.

19. Sources of drugs Natural Synthetic Plants/vegetable Semi synthetic Animal Synthetic Micro organisms   Mineral/chemical   Source of drugs:

20. Sources of drugs Synthetic source Plant/Vegetable source Animal source Microbiological source (microorganisms) Mineral / chemical Genetically engineered / bio-technology based drugs/ biopharmaceuticals/ biological agents

21. Plant sources: Alkaloids: Nitrogenous compounds of low molecular weight, basic naturally occurring organic compounds. They have definite physiological and pharmacological properties Mostly they are crystalline solids,insoluble in water but soluble in organic solvants Form salts with acids, which are soluble in water. Active ingredients of various plants. Contd.

22. Alkaloids examples : - Drug Source Part Use Atropine Atropa belladonna Bark & leaves  Anti-cholinergic Quinine & quinidine Cinchona Bark Anti-malarial Morphine Papaver somniferum Flowers (poppy) Opioid (narcotic analgesic) Reserpine Rauwolfia serpentina Roots Hypotensive agent Nicotine Tobacco Leaves Dependence* *To treat nicotine dependence in smokers in form of gums, dermal patches, lozenges, inhalers, nasal sprays. Alkaloids names usually end with “ine”.

23. 2. Glycosides : These are combinations of sugar with other organic structures. Sugar moiety is joined to a non-sugar moiety with an ether linkage (- o-) Sugar portion governs the pharmacokinetic characteristic of glycoside. On hydrolysis with mineral acids all glycoside split up into sugar and non-sugar residues . 1. sugar -o- non sugar –glycoside ( eg -digoxin) 2.Glucoside- sugar moiety is glucose . Glucose -o- non sugar -- glucoside 3. Aminoglycoside- sugar moiety is amino-sugar .(ex;streptomycin) amino sugars –o- non sugar - - aminoglycosides Contd .

24. Glycosides examples: - Digitoxin/ digoxin Digitalis purpurea Foxglove leaves Cardiac (arrhythmia) Ouabain Stropanthus gratus Roots, stems, leaves, and seeds. Cardiac (arrhythmia) Drug Source Part use

25. 3.Oils: Essential/volatile oils: Obtained from leaves or flower petals by steam distillation. Terpene derivative so these have aroma Steam volatile No food (caloric) value Do not form soaps with alkaloids Not become rancid (foul smell) on prolonged stay Mainly used as carminatives, astringents in mouth wash, or as flavoring agents. Contd.

26. Essential/volatile oils (contd.) Uses: Carminative: for expulsion of gas from stomach. Ex: - Ginger oil, eucalyptus oil. (act as irritant to gastric mucosa) Antiseptic: mouth washes. Ex: - Thymol. Flavoring agents: peppermint oil (diluent, solvent) Pain relieving agents: clove oil for toothache relief, wintergreen and turpentine oil for muscle pain relief (acts as counter irritant). * Some of them are solid at room temperature & sublimate on heating. Ex: - menthol, camphor.

27. II. Fixed oils: Obtained by solvent extraction of crushed seeds. Triglycerides Non volatile Have caloric or food value Form soaps with alkaloids Become rancid on prolonged stay Unsaturated from plants (saturated from animals) Little pharmacological use except for Castor oil – purgative Arachis oil – demulcent (removing inflammation or irritation). Ex: - Groundnut oil Coconut oil Olive oil

28. III. Mineral oils: obtained by dry distillation of wood Ex: - liquid paraffin used as lubricant laxative for promoting passage of stools.

29. 4.Gums: Colloidal exudates of plants .(secretory products) Either swell or dissolve or form adhesive mucilaginous colloids in water Used as emulsifying or suspending agents. Ex: - Gum acacia – acacia Senegal tree – emulsifier, texturing, dietary fiber and stabilizer. Gum tragacanth -shrubs of Astragalus species – stabilizer, emulsifier and thickener in food products.

30. 5. Tannins: Non-nitrogenous phenolic derivatives from plant source Soluble in water Mainly used as astringents. Ex: - Tincture catechu – Acacia catechu - precipitates proteins from cells of mucus membrane and thus exert a protective action. Tincture rhubarb – Rheum officinale – heal cold sores, reduces swelling, digestive complaints.

31. 6. Resins: They are formed by oxidation or polymerization of volatile oils Insoluble in water but soluble in alchol Tincture benzoin – used as antiseptic ,astringent and expectorants Oleoresin gums – mixture of volatile oil & resins. Ex: - Gum acacia –suspending and emulsifying and binding agents Other ex: Benzoin – inhalation in common cold . Colophony – an oleoresin used as an ingredient in various plasters. Shellac – Lucifera lacca derived, used for enteric coating of tablets. Contd.

32. Resins (contd.) Balsams: also, a type of resin, mixture of resin + benzoic acid + volatile oil. Ex : - Tolu balsam – Myroxylan balsamum - expectorant in cough mixtures, food & beverage flavoring agent. Balsam of Peru – Myroxylan balsamum – wounds and burns.

33. Some examples by parts of plants used as source: Leaves: Leaves of eucalyptus give oil of eucalyptus, important component of cold & cough syrup. (1,8-cineol & α - pinene ) Nicotiana tabacum leaves give nicotine, used in the forms of gums, dermal patches, lozenges, inhalers, nasal sprays to treat dependence, Parkinson's and anxiety. Atropa belladonna gives atropine- anti-cholinergic, OP poisoning.

34. II. Flowers: Papaver somniferum gives morphine ( cns depressent )used as narcotic analgesic (opioid- resin in poppies). Vinca rosea gives vincristine and vinblastine used as chemotherapy agents (leukemia) Rose gives rose water / hydrolat (tonic, essential oil)

35. III. Fruits: Senna pod from Cassia angustifolia gives hydroxyl-anthracene, which is a purgative (used as laxative in constipation). Calabar beans from Physostigma venenosum Balfour give physostigmine used in glaucoma (anti-cholinesterase activity) .

36. IV. Seeds: Seeds of nux vomica gives strychnine, CNS stimulant . d.Castor oil seeds Castor seeds give ricinoleic oil, used as laxative. Isabgol gives arabinose & xylose, used as laxative.

37. V. Roots: Ipecacuanha (ipecac) roots gives emetine, used to induce vomiting in accidental poisoning. Also has amoebicidal properties. Rauwolfia serpentine gives reserpine, used in hypertensive treatment.

38. VI. Bark: Cinchona bark gives quinine & quinidine(antiarrhythmic), used as anti-malarial drugs. Atropa belladonna gives atropine, used as opioid (anti-cholinergic). Hyoscyamus niger gives hyoscymine and henbane, used as anti-cholinergic.

39. VII. Stem: Chondrodendron tomentosum gives d- tubocuararine (skeletal muscle relaxant) used in general anesthesia.

40. VIII. Rhizomes: Ginger-cough and cold medicines Turmeric- antiseptic, antibacterial, coloring agent.

41. Animal sources: Many drugs are obtained from animal sources These comprise hormones, vitamins, vaccines and sera Gives

42. Hormones:

43. Vaccines: Blood of animals is used in preparation of vaccines. Ex: - Polio vaccine Anti-rabies vaccine Cholera vaccine BCG Small pox vaccine

44. Sera: Anti-tetanus sera (ATS) Anti- diptheric serum (ADS)

45. Vitamins: Vitamin A & D – halibut liver oil. Omega-3- fatty acids - cod liver oil. Vitamin b12 – liver extract.

46. Others: Cuttle fish bone used in tooth powder, when given internally it acts as an antacid. Shark liver oil prevent the damage caused by radiation used in treatment of cancer. Bees wax & honey from bees ( Apis mellifica ). Carminic acid a colorant from cochineal are the insect source. Epibatidine from skin extract of Ecuadorian poison frog possess analgesic activity. Venoms & toxins from snakes, spiders, scorpions, insects are extremely potent.

47. Microbiological source: Many antibiotics are obtained from the microorganisms. Some of the fungi, moulds , and bacteria are important sources of many lifesaving drugs . Natural : Mainly obtained from fungus,bacteria and actinomycetes Ex;pencillin,streptomycin Semisynthetic: chemically altered natural compound Ex‘; ampicillin,amikacin Synthetic: chemically designed in laboratory ex: norfloxin and moxifloxcin Contd.

48. Microbiological source(contd.): Examples: - Penicillin-g – pencillin notatum Chloramphenicol – streptomyces venezulae Streptomycin – streptomyces griseus Neomycin – streptomyces fradiae . Griesofulvin (antifungal) – pencilium griesofulvium Cephalexin – cephalosporium spp. Gentamycin – streptomycis Tobramycin – micromonosporas

49. Marine source: The quest for obtaining new medicines has gone beyond the terrestrial regions to the oceans & its flora & fauna Coral, sponges and marine microorganisms have a wealth of biologically potent chemicals with interesting inflammatory, anti-viral, and anti-cancer activity. contd …

50. Marine source(contd.) : Porphyran derived from porphyra species possess hypoglycemic, hypotensive, hypocholesterolemia and antiulcer activity . Curacin A, lipid constituent from a marine cyanobacterium Lyngbya majuscule shows potent anti-tumor activity. Eleutherobin from coral Eleutherobia spp. Also shows antitumor activity Discodermolide from caribbean marine sponge Discodermia dissolute- anticancer. Bryostatins from north carolina Bugula neritinia – preventing tumor growth Dolostatins from small marine gastropod mollusc Dolabella auricularia – antitumor Cephalostatins – broad class of bactericidal antibiotics from Cephalosporium acremonium fungus .

51. Mineral sources: Many Pharmacotherapeutic agents are obtained from mineral sources. These are solid/powder or liquid and mineral preparations. Contd.

52. I. Solid/ powder or liquid forms: Iron used in anaemia. Magnesium sulphate used as purgative. Milk of Magnesia – antacid, laxative. Aluminium hydroxide Calcium carbonate Antacids. Sodium bicarbonate kaolin (Aluminium silicate) – adsorbent in anti-diarrheal preparations . Contd.

53. Solid/ powder or liquid forms(contd.): Tincture iodine povidone iodine liquid mineral preparations used as antiseptics. zinc – zinc oxide oint . – Sunscreen, skin protection, eczema. Gold salts – Solganal , Auranofin - anti-inflammatory used in rheumatoid arthritis. Radioactive isotopes- radioactive 131 for diagnosis and treatment of thyrotoxicosis and thyroid malignancy.

54. II. Mineral preparations (miscellaneous sources): Obtained by dry distillation Vehicles for preparation of ointments Fluorine has antiseptic properties. Borax has antiseptic properties. Selenium as selenium sulphide is used in anti-dandruff shampoos. Mostly petroleum products. Hard & soft paraffin as purgative-laxative. Ex: - liquid paraffin.

55. Genetically engineered/ Biotechnology based/ Biopharmaceuticals/ Biological agents: Prepared by genetic engineering Recombinant DNA T echnology involves clevage of DNA by enzyme restriction endonucleases The desired gene is coupled to rapidly replicating DNA (viral, bacterial or plasmid) The new genetic combination is inserted into the bacterial cultures which allow production of vast amount of genetic material .

56. Genetically engineered/ biotechnology based/ biopharmaceuticals/ biological agents(contd.): Advantages are – Quality can be controlled Process is easier and cheaper More potent and safer Large scale production. Disadvantages are – Well-equipped lab is required. Highly trained staff is required It is a complex and complicated technique. Contd.

57. Genetically engineered/ biotechnology based/ biopharmaceuticals/ biological agents(contd.): Examples: - Hormones: human insulin ( humulin ), human growth hormone. Agent affecting immunity: vaccines such as hepatitis-b vaccine ( recombinax-hb ) and interferons. Thrombolytics : Alteplase , Reteplase . Clotting factors: factors VIII and IX. Blood growth factors: human erythropoietin, platelet derived growth factor.

58. Monoclonal antibodies: Numerous monoclonal antibodies have been synthesized to be used for various purposes Ex: - Gemtuzumab (CD3), Alemtuzumab (CD52), Infliximab and Adalimumab ( tnf α) etc.

59. Synthetic source:(purely chemical) When the nucleus of the drug from natural sources as well as its chemical structure is altered, we call it synthetic. Presently majority of drugs are obtained synthetically Some of drugs which are earlier obtained from plant sources are synthesized in lab. Example Trade name Classification Meperidine Demerol Analgesic Diphenoxylate Lomotil Antidiarrheal Co- trimoxazole Septran Sulfonamide ( rx of uti’s )

60. Semi synthetic: When the nucleus of drug obtained from natural source is retained, but the chemical structure is altered, we call it semi-synthetic. These are mainly obtained by changing the chemical structure of naturally obtaining drugs. Most of the drugs used nowadays (such as anti-anxiety, anti- convulsants ) are semi synthetic forms. Ex: - Penicillin substrates Atropine bromide Apomorphine Diacetyl morphine Ethinyl estradiol Homatropine Ampicillin and Methyl testosterone.

61. Summary Pharmacology, Pharmacognosy and drug definitions. N ature of drugs based on physical nature, form and actions. Classification of sources of drugs based on sourcing and modes of preparation.

62. references Trevor, K. (2022) basic & clinical pharmacology 13th edition . Mc G raw Hi ll India. HL Sharma & KK Sharma. 2017. Principles of Pharmacology 3 rd edition. Paras medical publisher Hyderabad. P. 7-9. Laurence L. Brunton.2018. Goodman & Gilman’s. The Pharmacological basis of therapeutics. Randa Hilal -Dandan, Bjorn C. Knollmann , editors. 13 th edition. Mc Graw Hill India. P.3,4. SK Srivastava, Rohan Srivastava. 2021. Pharmacology for MBBS. 2nd edition. Avichal publishing company, New Delhi. P.4,5.